Leaders in Pharmaceutical Business Intelligence (LPBI) Group

A Patient’s Perspective: On Open Heart Surgery from Diagnosis and Intervention to Recovery – A New Day, a New Lease and Unfolding Questions!

Guest Author: Ferez S. Nallaseth, Ph.D.

Life Sciences Institute of New Jersey, Belle Mead, NJ 08502; Complex Biological Systems Alliance, Boston, MA; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08901.

Contact information:

Email Addresses: ferez.nallaseth@cbsaimtt.com

ferez.nallaseth@gmail.com

Tel: 646 283 5163 (M)
908 431 5069 (CBSA)
Skype Address: ferez.nallaseth
Websites:Life Sciences Institute of New Jersey, Belle Mead, NJ.
Member – Complex Biological Systems Alliance
Ferez S. Nallaseth, Ph.D. (Google Scholar)
Ferez S. Nallaseth, Ph.D. (Google Sites)
Ferez’nSquashDocs (website and blog)
LinkedIn:http://www.linkedin.com/pub/ferez-soli-nallaseth/14/2a7/311
Twitter:@fnallase1

This article will be published in 

Series E: Patient-Centered Medicine 

Volume One: The Patient’s Voice: Personal Experience with Invasive Medical Procedures

All subsequent excerpt submissions for publications elsewhere MUST include the following sentence:

START QUOTE

I, Ferez Nallaseth, PhD was commissioned (at no exchange of any financial rewards) by Dr. Aviva Lev-Ari, PhD, RN, the Editor-in-Chief of the Open Access Online Scientific Journal 

http://pharmaceuticalintelligence.com

on 2/14/2015 to write an original article representing “The Voice of the Cardiovascular Diseased Patient who underwent an invasive procedure, i.e. CABG, aka, Open Heart Surgery.”

Date: Sat, Feb 14, 2015 at 5:37 AM

Subject: Invitation to write one article about your experience: From Diagnosis to Recovary

To: Ferez Nallaseth <ferez.nallaseth@gmail.com>

Cc: Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu>

We are publishers of a BioMed e-Books e-Series

Please go to

Http://pharmaceuticalintelligence.com

Click on

BioMed e-Series

1. Please click on Series A: Cardiovascular Diseases

Volume 1,2,3,4,5,6

2. Please Click on Series E: Patient-Centered Medicine

Volume One: The Patient Voice – Experience with Invasive Surgery

HERE, I WISH TO INVITE YOU TO CONTRIBUTE ONE ARTICLE ON YOUR EXPERIENCE WITH OPEN HEART SURGERY.

Please reply if interested.

I am looking forward to your reply.

Aviva Lev-Ari, PhD, RN

Editor-in-Chief BioMed Series

• This article was edited by Stephen J Wiiliams, PhD, Senior Editor at Leaders in Pharmaceutical Business Intelligence (LPBI) as part of the publishing process of the article in the Journal.

This article was published in the Journal on May 10, 2015. This article will appear in the forthcoming ebook, Titled, 

• Volume One: The Patient’s Voice: Personal Experience with Invasive Medical Procedures

 This is Volume One in Series E: Patient-centered Medicine, in the BioMed e-Series will be published by LPBI on Amazon.com

The URL for the original article is listed, below:

http://pharmaceuticalintelligence.com/2015/05/10/a-patients-perspective-on-open-heart-surgery-from-diagnosis-and-intervention-to-recovery/

END QUOTE

• All References to the article as a Reference source, should cite the link, above

HOWEVER, since this article has been included already in Volume One of Series E AND Volume One is WORK-IN-PROGRESS, not yet on Amazon.com as a published e-Book THEN 

• for all cases of using an excerpt versus citing the article in its entirety for ANY OTHER PUBLISHER, i.e. Squash Report, it needs to add a footnote with the QUOTE, above

A Patient’s Perspective: On Open Heart Surgery from Diagnosis and Intervention to Recovery – A New Day, a New Lease and Unfolding Questions!

Ferez S. Nallaseth, Ph.D.

Life Sciences Institute of New Jersey, Belle Mead, NJ 08502; Complex Biological Systems Alliance, Boston, MA; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08901.

ABSTRACT:

A minor cardiac event last Christmas revealed how seriously my life was threatened. It was averted by the amazing efforts of the, Biomedical Community, Family, Friends and Colleagues all pulling together and from around the Globe. The brush with ‘eternity and infinity’ left me aware that the ‘just war’ in which I had been engaged for close to 4 decades had left too much not done and too many, neglected in too many ways and too far removed from the core of my being! At least part of the consequences of that trauma on the 25^th of December was the initiation of a thought process (or the lack of it) in filling this void! And yet remaining mindful of history and those in it, even ordinary ones, to whom we owe so much, precisely because they made the right and hard, choices that I am faced with today!

SYNOPSIS:

This is the perspective of a Life Scientist who underwent a Heart Attack and triple Bypass Surgery. Because this is a retrospective experience with little data to support it and I am neither a Cardiologist nor a Cardiac Surgeon, this exercise is of necessity, a largely subjective delivery of the process that saved my life. It is one in which I was merely the beneficiary of the highest form of dedicated professionalism! It is in part an expression of my deepest gratitude to my family, friends, some even emerging from long neglect, and medical professionals who leapt to my rescue! As well as addressing a need for more systematized studies to address the true frequencies of the events that I underwent. A gratitude that usually dawns when one has had a brush with ‘eternity and infinity’ and effectively becomes bedridden – if only transiently so! Considering the technical complexity of the undertaking by (a) Dr. Andrew Shanahan, my Cardiologist, in detecting the block by catheterization and angiography and (b) Dr. George Batsides, my Cardiac Surgeon and (c) their respective teams in intervening with the triple bypass surgery, all with a 98% success rate, it is nothing short of amazing!

However, the scientific and medical literature and my Cardiologist’s and Cardiac Surgeon’s observations also supports the interpretation, although not experimentally verifiable, that competitive Squash and training for it in India delayed Coronary Artery Disease and kept me alive till Dr. Shanahan and Dr. Batsides had time to intervene! It probably saved my life in 3 important ways. Firstly, as 1 of about 20 high intensity sports (METs of 6 -13) it is likely to have significantly lowered the risk of Coronary Disease (22 – 40%), thus secondly, delaying the massive blockage (95% – 99%) of 5 major Coronary Arteries by Coronary Artery Disease (CAD) that was recorded. Lastly Squash, and training for it, likely preconditioned (Ischemic Preconditioning or IPC) my cardiomyocytes, making them resistant to hypoxia and so ensured their predominant survival (96 – 98%) when the inevitable Heart Attack (Myocardial Infarction or MI) predicted by several Risk Factors, occurred. However, the ~2% of cardiomyocytes which did succumb to cell death could not have been resistant to total Oxygen (O₂) deprivation (anoxia) as is expected e.g.from observations in Sudden Cardiac Arrest (SCA). Conversely, the hypoxia resistance of my cardiomyocytes may have contributed to the inability to stress them with O₂ deprivation in Stress Tests as was revealed by Electrocardiograms, Transthoracic Echocardiography and Electroradiographic monitoring. This may have, despite chest spasms, led to the inability to detect the disease over 10 years. Only catheterization and angiography, justified by the elevation of circulating levels of the biomarker Troponin T and done by Dr. Shanahan could confirm this dire Coronary Artery Disease diagnosis.

Although an attempt has been made to include, (1) useful information recommended by all the Medical Personnel involved who have previewed an outline of this article, (2) select scientific and medical literature relevant to it have been added to each of the contributing dimensions that were considered (but are restricted to Supplementary Information Boxes (SIB)), (3) those lifelong events, activities and habits (including the assault on my professional work and personal life) that either contributed to or ameliorated known Risk Factors for the Heart Attack which on hindsight was inevitable! At the very least the combination of my decades long cardiac and sports experience, the scientific literature and the findings of Dr. Shanahan and Dr. Batsides after I finally had a Heart Attack, as well as the experience of others in the Cardiac Physiotherapy Program that I attend, strongly suggest a need for a systematic screening for these symptoms. Of necessity preceded by a re-evaluation of the methods for detection of all types of silent diseases affecting the Cardiac system.  For example development of various Tomography approaches e.g. Multi Spectral Optoacoustic Tomography (MSOT) (97,98).

I’ve also made an attempt to come to terms with perhaps an insidious process that is still underway – somewhere in the back of my mind. It may mimic the ‘know thyself’ of Delphos, and what I like to think of as the nebulous, amorphous and often contradictory aspects of being human. This includes the many communities in any life – family, friends, medical, professional and social networks. Those who were either at one with me or dropped everything in their own lives to leap to my rescue, and also included onlookers and even outright adversaries who seemed to be genuinely concerned! Possibly transfixed by the specter of mortality?

Work unfinished due to unavoidable circumstances that were alluded to earlier and the transience of life were the compelling, if sub conscious, forces over the past 40 years or so and although now dampened by these events, they have not disappeared. And in some unclear ways may perhaps even have been heightened in my sub-conscious by the potential extent of the waste of my life if things had ended less favorably. Not only of the terminated future, but also of the long span of the past which had been dedicated to the body of unpublished Scientific work, which would have been discarded instead of being in the literature where it serves a more useful purpose!

However, the true nature and impact of the recent events on my life and their effects go beyond the Operating (Surgical) Theater and are still evolving! Included are a revision of the cavalier considerations of activities and habits contributing to cardiac Risk Factors with ‘you only live once’ which have now been tempered by that brush! A temperance into both, a reticence that is almost Pavlovian as well as one of a sense of responsibility to those whose graciousness, generosity, sacrifice and hard work rescued me from near certain death! In addition to those Physicians and Surgeons who played the most active roles in saving my life, all those unbelievably dedicated Biomedical Support Personnel who assiduously contributed to the diagnosis, intervention and recovery of a relative stranger who had undergone a Heart Attack and required Critical Care are included here. They are implicitly or explicitly noted in the acknowledgements (link). This event and the period spanning it will remain a watershed that has unleashed many ongoing developments in my life.

INTRODUCTION:

Last Christmas morning (25^th December 2014) would become a Watershed Day in my life! Although I had, what was subsequently confirmed as, only a minor Heart Attack (Myocardial Infarction), it unleashed a progression of events that culminated in Open Heart Surgery. They continue to alter my perspectives radically, and in ways, with which I am still coming to terms. For a start it conclusively resolved the “Will-O’–the-Wisp” of Chest Pains and Diagnoses’ that ‘ruled out’ Cardiac malfunctions over the last 10 years. There were other ways in which it does so but this followed more (bad but good) news that was yet to come. When I was brought in by the Emergency Medical Services the Biomedical teams in the Emergency Room of the University Medical Center of Princeton in Plainfield, led by Chief Emergency Physician Dr. Eileen Daly, the Attending Physician Dr. Ying-Kei Hui and the Cardiologist Dr. Banu Mahalingam immediately concentrated on stabilizing my condition, the seriousness of which I alone was not fully aware! And more on this effort was to follow. I looked on all this as an inconvenience and planned on getting back to my keyboard – sooner than later. It would be nearly a month before I had finally managed to have done so – and likely would not have been writing this if I had been allowed to have my way! Since this is meant to address the concerns of those Patients who will follow in my experience I think it would be useful to define an outline of this article that the Editor of BioMed Online (Cancer, Cardiology, and Cardiology Devices) Dr. Aviva Lev-Ari had asked me to write. First of all the simple question arises as to why, as a Scientist who depends on controlled experiments, I would even agree to write something that is so subjective an experience? The short, if incomplete answer, is gratitude! For those who kept me alive medically and my family members and friends who dropped everything in their lives to either appear by my side or write and some even reappear in my life! And of equal importance these events convey a need that has been identified by others like myself – for a systematic and controlled study to address the gaps in a system that is otherwise remarkably fail safe!

But to address this and other questions meaningfully, it would be useful to deliver this narrative in (1) a chronological order, (2) while making necessary diversions with supplemental information boxes (SIB) included for short informative discussions on the, (a) literature on e.g., Risk Factors and rudimentary Cardiology and Cardiac Surgery, (b) definitions and analyses such as, (c) vital signs that may have made revelations about the process and why cause and effect as scientific and medical conclusions are unknowable in my case, (d) pain from Open Heart Surgery, (e) compassion, warmth, concern and yet skill, dedication and professionalism of all the Biomedical personnel involved, (3) summary of the relevant literature on contemporary methods of (a) establishing Risk Factors, (b) the energetics and physiology behind the cardio-pulmonary system, (c) the molecular, cellular and developmental biology of the cardiac system, its protection from genotoxic shock and disease states, (d) the contribution of specific processes to Risk Factors as well as their amelioration, (e) Sports Physiology and the role of Sports with an emphasis on Squash in the reduction of cardiac Risk Factors, (4) a summary on elements of the literature and the observations of my Cardiologist and Cardiac Surgeon that are consistent with the explanations for the events – first slowing down plaque buildup and then protecting my cardiomyocytes and allowing survival from the Myocardial Infarction (MI) or Heart Attack, (5) acknowledgement of those who either saved or eased my life, (6) reference list, (7) a more detailed review of this article focused on Sports Physiology and Cardiac Risk Factors to be oriented and submitted to a Sports or Clinical Sports Journal (1).

(8) (a) To begin with, it is only appropriate to thank my Cardiologist Dr. Andrew Shanahan and my Cardio -Thoracic Surgeon Dr. George Batsides. Dr. Batsides’ highly encouraging message to my query for permission to publish an event that involved his work, his team as well as his Editorial assistance:

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(8)(b) this article has additional input, (i) from concerned, highly skilled, dedicated, kind and professional, Biomedical Staff, Physicians and Surgeons at both the University Medical Center of Princeton (UMCP) in Plainsboro as well as at the Robert Wood Johnson University Hospital (RWJUH) in New Brunswick, (ii) my Family, and Friends, including my brother Attorney Cyrus Nallaseth who flew in from Bombay, (Mumbai) India on a moment’s notice, family, friends spanning generations such as Dr. Adil Mulla, an Anesthesiologist and his daughter Dr. Simone Mulla, who either appeared by my side or called regularly, at a vanishingly short notice, (iii) a long list of the most warm, kind, supportive and encouraging friends, fellow Squash Players, Scientists, fellow LinkedIn Members, fellow ResearchGate Members, Teachers at Princeton High School and others from around the World who responded via email to my ‘Late New Year’s Greetings’ and postings of the news, with nothing but the most supportive words that were re-invigorating in ways that I could not even have imagined! They are all listed in the acknowledgements link! In addition the article attempts to recognize as many contributors as were identifiable (with apologies included for any inadvertent omissions). This narrative will of necessity require covering the Risk Factors for Cardiac Disease that were both imposed or unavoidable and inevitably led to the cardiac event of the 25^th of December 2014. As well as the ones that were those that I had either exacerbated or ameliorated. This will follow after introducing a few events in chronological order.

(A) NARRATIVE: A CHRONOLOGY OF LANDMARK EVENTS:

     1. Pre Heart Attack symptoms.

Over the last 10 years or so, prior to the Heart Attack, I had fleeting spasms in different locations of my chest and even while at rest. Depending on the circumstances e.g. acute stress, I had always had digestive and neurophysiological symptoms that are recognized as stress and environment related. They could either mask or promote cardiac pathologies. Approximately 35% of the US population displays all or some of these and other related symptoms (2). Furthermore, my colleague Peter Shimon of the Darwinian Evolutionary Medicine Group on LinkedIn identified a publication noting that Historians had recorded that these stress related symptoms, although near incapacitating, were overcome by those associated with the creative characteristics common to many artists, scientists and others, including Charles Darwin (3a,b)! In fact Darwin continued working, while having to solely depend on the ineffective therapies of his time, such as cold compresses applied to the spine. He wrote a whole chapter in the ‘Descent of Man’ while immersed in ice water to relieve the grip of nausea and migraine! (3a). It was, what we call, ‘Mind over Biology’ in the World of Sports!

As far as the spasms in my chest went, initially I did not think much of them but from around 2004 onwards, consulted Cardiologists and had gone through several Stress and other tests which were negative for cardiac malfunction that they had administered over that period. So it was hard to diagnose the cause of those chest spasms and my Primary Care Physician Dr. Perry Pong reminded me to remain wary of pulsating pains in the area of the sternum but not to worry too much about the other areas. Advice that was to save my life!

     2. Did Overtraining in my competitive Squash playing days lower the Risk Factors for Heart Disease through Ischemic Preconditioning (IPC)?

I had trained hard (in Sports Physiology this is termed over-training) in India 38 years ago (up to 1976 when I left for the US) for competitive Squash, an intense sport (~ 20 of 100 sports with a near maximal Metabolic Equivalent Task (METs) of 6 to 12). From results in national level tournaments, I was in the top 10 and remained in good shape even after decades of detraining an example of the training regimen I used was posted for the Rutgers University Squash Racquets Club (and this will matter as we will see later) (4). In the United States, after I had lived for 13 years in small University towns, which due to a lack of competition, essentially resulted in detraining, my game had ceased to exist and conditioning had dropped irreversibly to a fraction of the level in India along with my performance on the court. This happens to the best of Racquet Athletes who detrain relatively early in their careers e.g. Wimbledon and multiple (near) Grand Slam Tennis Champion Bjorn Borg! However, I still regained some of this conditioning, on subsequent retraining, with new literature referenced and to be discussed in this article, providing a molecular and cellular mechanistic basis for this observation – one which has always been well known to Athletes.

After moving up to the New York area in 1989 my game was partially recovered and I was nationally ranked in the USA in 1992 as a 40 year old (top 20 in the 5.5 level and higher in other age group divisions, by US Squash). Even in 2006/2007 long after my prime when I was 54/55 the residual game and conditioning retained were still sufficient to secure semi-final and final level performances in Open tournaments in New York (at 5.0 or Ltd A levels – 3 levels down from the highest 6.0 level)! As well as a 3 -2 win over a top ranked (by US Squash) Amateur/Pro (6.0 level) level competitor, Shane Doyle in a tough 90 minute interclub match. I was playing for the Rutgers USRC against Francis Odeh’s Valkyrie Club. Shane was an All American Surf Boarder and one of the toughest players in this semi-contact sport whom I have ever played in the United States! This may mean that 30 years after ceasing high intensity training, I still retained some of the conditioning developed in India. Squash, has been rated as having the highest Exercise Intensity (METs = 6 -12 cals/kg/hr), Health Benefit to Injury Ratios (517 Calories per 30 minutes of a game to Injury Score of 2) and Healthiest Sport with a total score of 22.5 of 10 sports as measured by Sports Physiologists, Athletes and Coaches (5, 6). And so a lifetime of conditioning in Squash, was likely to have contributed to my cardiac conditioning and saved my life (as will be shown later). However, after 2006/2007, I was again professionally pre-occupied and despite perfunctory workouts in the local gym my game and conditioning deteriorated further to low levels. This is dealt with in greater detail in the final segment.

     3. Did I have a Heart Attack in April 2010 long before the one on December 2014 that could not be detected by all the tests for cardiac malfunction that were administered?

At some time in April 2010, while on the court, I had a prolonged (1- 2 minute) chest spasm of medium intensity. Dr. Pong and I decided it was time to have it thoroughly examined by a Cardiologist. The Cardiologist whom we consulted was Dr.Tak Kwan. He was methodical, dedicated, reassuring, skilled and professional! I was subjected to 4 tests that were considered to constitute a thorough analyses of cardiac malfunctions. They were:

• Electrocardiogram
• Transthoracic Echocardiography (without 2D, color flow Doppler Echocardiography)
• Transthoracic Echocardiography (with 2D, color flow Doppler Echocardiography)
• Exercise Myocardial Perfusion Imaging with Dual Isotopes SPECT (Gated Tomography) or Electroradiographic monitoring for 24 hours

Based on the results of these 4 tests Dr. Kwan excluded cardiac mal-function with a 95% confidence interval. He felt that the Health Insurance Provider would not authorize any further more definitive tests such as catheterization and angiography. And subsequent events on the 25^th of December 2014 confirmed the elusive nature of detecting even an ongoing Myocardial infarction (Heart Attack) which supported his conclusion.

As I was not a Cardiologist, there was little more that I could do and since I did not want to become a hypochondriac, I stopped thinking about this problem and did what we are trained to do in our time as athletes! That is work our way through ‘Pain Barriers’ as defined by the Multiple British Open Squash Champion, Jonah Barrington, in the 1970s (7). Although to be honest this level of pain would qualify for discomfort – at best!

That is till about 8.00 am on Christmas morning of 2014. I was on the computer keyboard – probably checking the Online News when things began to happen! The circumstances became reminiscent of my father’s passing from the second and fatal of two Ventricular Fibrillations that he suffered which was far more traumatic than my Heart Attack.

(B) HAVING POSSIBLE SYMPTOMS OF A HEART ATTACK (MYOCARDIAL INFARCTION):

(I) My apartment on Christmas day of 2014:

(i) On holidays I made a conscious effort to try and forget the ‘Elephant in the Room’ (‘EitR’ to be explained). Since one of its latest consequences was a lack of a job and funds for the past 8 (and often in the last 35) years my entertainment was restricted to consumption and TV at home. On that day this included Appetizers, Breads, Liquors, Prime Rib, Vegetables, Mashed Potatoes, and Christmas Plum Pudding with Plum Sauce! It was a good meal and sampling began on Christmas Eve (12/24/2014) although its leftovers were anticipated to last through the holidays – and well past New Year’s day!

The lipids and calories associated with this meal when either consumed in excess or regularly are classified as Risk Factors by the American Heart Association, the National Heart, Lung and Blood Institute of the national Institutes of Health and the Centers for Disease Control (CDC), the New York State Department Of Health and the Mayo Clinic Health System] as representing significant Risk Factors for Coronary Heart Disease (CHD), Coronary Artery Disease (CAD) and Coronary Vein Disease (8 – 26). The multifactorial nature (gene, environment, etc..) of heart disease(s) has always made it difficult for Cardiologists to identify and evaluate the impact of Risk Factors. However, contemporary genetic and statistical methods which are far more comprehensive as well as of higher resolution are accepted as reliably identifying and quantifying the Risk Factors associated with cardiac diseases (SIB-1, 7A to 7D). Included are the Risk Factors that my life style clearly incurred and those that it ameliorated.

The above meal was a Risk Factor! However it was a needed the distraction, could not be afforded often enough for it to amount to a dangerous Risk Factor, there were routinely included counteractive measures (workouts, statins, diet, etc..) and after all one only lived once! As we will see shortly, this led to an enforced leave of absence for 3 weeks in the Hospital, I ended up giving away, returning or discarding all the ‘good stuff’ – and may have not lived long enough to write this article!

(narrative interrupted).

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(narrative resumed).

(ii) How many of the Risk Factors identified in SIB-1 were exacerbated and how many were ameliorated by my life style? The answer is mixed. Although as many as 5 of 10 Risk Factors listed by the NHLB, NIH, including moderately high cholesterol, decreased level of physical activity, being a little (20lbs/9kg) overweight, a history of a somewhat unhealthy diet (fast foods for 20 years, but home cooked for the most recent 15 years), and family history of heart disease and even early death from it (all 4 of us in the immediate and others in the extended family) apparently applied but were qualified. However, both family history and physical inactivity were ameliorated by overriding non-genetic factors and somewhat regular workouts. At least 3 more Risk Factors, gender, stress and uncontrolled anger (for good reason) being drawn from the list assembled by the NHS (UK) and WebMD applied to some degree. However determining the Risk Factors contributing to my MI or Heart Attack cannot go far without first addressing the ‘Elephant in the Room,’ (EitR), that had to have contributed heavily to the events under discussion! This is only alluded to once in this article, if for no other reason than to restore attention to those whom it belongs – the Biomedical Community, my family, friends and colleagues from all walks, who in different ways, either set aside all their concerns or preoccupations or focused their occupations, and leapt to save my life!

To understand the magnitude of the pressures from my professional life that had to have been a major contributor to stress as a Risk Factor, events spanning the last 35 years, and still ongoing, require being sketched. To protect something that was well established in Evolutionary Genetics and which led to discoveries of a fundamental Scientific importance and so to the Public Interest, (56, 57), I had to endure a multi-dimensional assault for largely venal reasons! First on our work and then, when an honest editor Dr. Walter Fitch finally published it, on me personally! Our work was first misunderstood by those who should have been more familiar with the literature, then eagerly sought by those at top labs and universities. The assault was coordinated from the highest levels of science by someone at the very pinnacle of scientific authority who was then at a major Research Institution/University in Boston, and had invited me to give a seminar on my work. From hindsight it was clearly with the intent of handing our work over to the designated ‘chosen’ in the field – a long term habit for which all the Principal Investigators involved in this process were infamous! This Investigator was proven to be one of the most unethical and ruthless Scientists in History by a US Congressman, by the National Institute of Health’s Office of Research Integrity (ORI) as well as by the President of an Ivy League University who Chaired a separate Committee Ruling on the events and reported that what had been documented was “only the most visible” of events. All this until a reversal was forced under pressure from the HHS!

In the spectrum of hostile actions taken against us the willing participation, of colleagues and even bystanders from the scientific community, who should have been more trustworthy, was secured! Yes, given the nature of the threat (combined with the prods of incitement and ingratiation!) there were consequences for refusing to participate, but let us just say that the actions of these scientists did not quite amount to upholding the Public Interest. Let alone, amounting to the resistance of, Dr. Robert Oppenheimer to the House Committee on Un-American Activities, or of Dr. Albert Einstein to the Nazis, or of Dr. Andrei Sakharov to the Soviet Politburo and its KGB. And most of all of Dr.Nikolai Vavilov (and his students) who endowed Humankind with Agricultural Biodiversity as well as with their own lives in their resistance to Trofim Lysenko, Lavrenty Beria, Joseph Stalin’s NKVD or the Nazis (during the Siege of Leningrad)!

The only way for me to have protected the Public Interest in our work and yet to have dealt with the ‘EitR’ was to become single minded, developed a thick skin, innovated, resisted attempts at cooption and continued grinding. As can be imagined, that meant losing many things large and small which took a toll finally even including my health! I had obviously concluded that this work was of large enough importance to persevere, if only reluctantly so, and to incur their wrath! However, unfolding results and events clearly supported this conclusion (56, 57)! And so it was always on the back of if my mind including on that morning of the 25^th of December 2014.

Although, given its magnitude, prevalence and duration, it is of critical importance, the literature makes it unlikely that this assault on my scientific career and my person was the sole Risk Factor in the Coronary Event of 12/25/2014. As will be clear from the literature these Risk Factors were also likely to have been ameliorated by my having competed and trained hard (overtraining) for the high intensity (METs index of 6 to 12 cals/kg/hr) sport of Squash Rackets. The literature shows that this activity probably resulted in my cardiomyocytes being preconditioned to hypoxia resistance by a process known as ischemic preconditioning (IPC). This IPC can either last or be restored even after long periods of detraining. It also probably lowered the Risk Factors for Coronary Artery Disease (CAD) by 22 – 40% and so slowed down the buildup of plaque from CAD that was underway until the inevitable accumulation of plaques attained 95 – 99% blockage in 5 major coronary arteries as will be documented later. Together with the afore mentioned pressures this CAD inevitably led to the Heart Attack (Myocardial Infarction or MI) on the 25^th of December 2014. But again, probably at a much later point in my life, and when it did occur, the MI was minor as ~98% of the (IPC) preconditioned cardiomyocytes survived. Only ~2% of the cardiomyocytes succumbed, as determined by Dr. Andrew Shanahan (using angiography and acoustic methods) and they probably succumbed to anoxia. This preconditioning induced hypoxia tolerance of cardiomyocytes also explains the inability of Cardiologists to detect cardiac malfunctions in Stress Tests over 10 years and so detect the developing CAD probably underlying my chest spasms. It is based on the proven retention of overtraining derived hypoxia tolerance even after a prolonged period of detraining (67). Another factor is the number of new cardiomyocytes born in periods of low or no training calculated from Retrospective Birth Dating (RBD) studies of Dr. Jonas Frisén and his colleagues (58, 59). RBD could have resulted in the maximal replacement of ~4.4% of cardiomyocytes leaving them susceptible hypoxia in the event that IPC was not transferred. However, an alternative explanation is also possible. Those ~2% of cardiomyocytes which succumbed could have done so because they were resident in a cardiac segment that lacked any blood and Oxygen (O₂) supply and so were completely anoxic which results in lethality within 5 minutes.

(iii) After my second cup of coffee on Christmas morning, things started going South – but it was still nothing to cause panic! They were all routine digestive and neurophysiological symptoms that were handled before! For example by appropriate titrations of doses of medications and foods – or so I thought!

(iv) I started feeling nauseous, broke out in a cold sweat, vomited, became lightheaded and thought I was passing out, but lay down and recovered. And most differently of all, shortly before 8.00 am, now felt the pulsating beat below the sternum that Dr. Pong had warned me about staying alert. Somewhere along the way I realized that the Emergency Medical Services (EMS) of Princeton might be needed and so dialed: 911. As it turned out this decision ‘not to tough it’ was another one that probably saved my life!

(v) The Princeton EMS personnel were at my apartment in next to no time (about 8.15 – 8.20 am). I had recovered by then, and so could let them in. The Heart Attack, as would be confirmed later, from the time of detection of the Troponin T marker, had probably occurred in this time frame. They checked my vital signs (blood pressure, pulse, heart rate, temperature, etc..) and decided that I had to go into the Emergency Room – they suggested the University Medical Center of Princeton at Plainsboro (UMCP). It turned out to be a very good choice! The EMS personnel kept a close watch, and constantly engaged me in conversation while checking for the vital signs, every 1- 2 miles as we went north up highway US 206 which I knew well! I felt fine – but realized it was time to find a different less destructive distraction to the ‘EitR’!

(A)     THE EMERGENCY ROOM OF THE UNIVERSITY MEDICAL CENTER OF PRINCETON AT PLAINSBORO (UMCP):

(i)     We arrived around 8.50 am and by 9.00 am I was in the Emergency Room! With the Nurses and Dr. Shivani Sharma taking my recent and family History for the Charts, a technologist recorded my Electro Cardio Gram (ECG), and vital signs, a technologist drawing blood for the Pathology Lab for the quantification of Lipid Panels, Enzyme and Troponin T markers testing whether a Heart Attack had occurred. My charts show that I was placed on the usual combinations of Blood Thinners, Nitroglycerin paste, Protonix, Aspirin, Statins, etc.. to stabilize the condition resulting from a Heart Attack.

(ii)     Troponin T is a marker which is accepted as 100% diagnostic for a Heart Attack (Myocardial Infarction). Blood drawn at ~ 9.00 am did not show an elevation of this marker. This is not surprising as it takes 2 – 4 hours after onset of Chest Pains to be elevated to detectable levels in the bloodstream and then can lasts at elevated levels for 7 days (15, 18).

(narrative interrupted).

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(narrative resumed).

(iii)     The Electrocardiogram (ECG) traced at 10.40 am confirmed an irregularity. X-rays were taken. The Attending Physician listed on the charts was Dr. Ying – Kei Hui and the Head Physician of the Emergency Room was Dr. Eileen Daly. I was in good hands and most of my early interactions on the 25^th of December were with Dr. Shivani, Dr. Daly and their supporting Nurses and Staff.

(iv)     The cell phone rang – my cousin Carl Engineer from San Francisco and his family, wife Dina, son Jehan, daughter Nisha and Son-in-Law (to be shortly), Chris Johnson, broke out in a Christmas Carol! Most of us are not religious, although I was raised in a Jesuit School and our family includes members from a multitude of religions, persuasions and nations, but we do know, as is obvious, a good time! And Christmas brought it whether we were in Bombay or London or New York or San Francisco! And I was not about to let on and ruin it – gaining the Nurses silence during the call! Particularly since over the last 10 years chest pains and stress tests had all turned out to be negative for cardiac mal-function ! By this point my thoughts had drifted back to the keyboard – TV worked as a distraction for about 10 minutes!

(v)     At 2.00 pm the batteries of Tests were administered again. This would soon become an hourly fixture and if anything multiplied in numbers and varieties over the next 3 weeks. The Troponin T level was now detectable at 0.11 ng/ml! Thus ending the ‘Willo-the-Wisp’ of the last 10 years and confirming that a Heart Attack had occurred! Based on the time of appearance of Troponin T, the MI may have been those pulsating spasms below the Sternum that occurred between 8.00 am and 9.00 am when I was still in the apartment! This result changed my life irreversibly! Dr. Daly came in and exclaimed ‘you see there is a method to our madness’ – obviously referring to the wait showing that the Troponin T finally rose to detectable levels as well as to my question about the period of time I would have to stay in the hospital.

(vi)     I was now moved up to the 3^rd Floor in the Telemetry Wing for patients requiring either Cardiac Care or Intensive Care Units, fitted with a mobile Heart Rate Monitor which transmits signals that are recorded in a Central Station. The Monitor of the Central Station reports any loss of signal (e.g. wires coming loose from the patient or worse) and a Nurse corrects the problem immediately. The rigor was impressive!

(vii)     Dr. Daly came back took one look and said ‘look at you – cool as a cucumber’! What she could not have known, was that although I am not known to be slow, when it comes to these large, if not monumental events, I tend not to react, as there is not much to do that can change things! An example of a monumental event was represented by the time when I lived with my brother’s family 2 blocks away from the World Trade Center on 9/11 and we heard the first Plane [via Brooklyn fly over and into the North Tower, then waited, kept watch with those who had loved ones in the North Tower, until it collapsed and we had to run from the rush of debris!]. Also by this point, (and Dr. Daly could not have possibly known), my thoughts had positively drifted back to the keyboard – little did I know what lay ahead!

(viii)     Blood drawn at 9.00 pm showed that the Troponin T level further risen to 0.19 ng/ml which is considered high. On 12/27/2014 it had spiked at 0.47 ng/ml before gradually returning to 0.19 ng/ml and then to basal levels in responding to treatment.

(ix)     The Nurses were all in smart uniforms and I thought this was a Christmas Day informal uniform free day – until told with a smile, that it was a regular uniform! Through the night my vital signs were monitored, blood was drawn, medications administered and electronic records updated – like clockwork!

(x)     The next morning I had the pleasure of meeting Dr. Hui and Dr. Mahalingam who went about their usual responsibilities but were warm and empathetic while remaining professional. However, as soon as I asked Dr. Mahalingam about going home I was read the ‘Riot Act’ seemingly reserved for Coronary Patients – she might have been primed. Basically she explained how quickly even a mild Heart Attack, which is what I seem to have had, can turn into one like that which left a current occupant of the ICU hanging by a thread. And we were soon to find out exactly how right she was!

(xi)     It had been decided that a catheterization and angiography was now justifiable as it would reveal more information about the condition of the Heart and its Coronary blood vessels. Dr. Andrew Shanahan who was Dr. Mahalingam’s colleague at the Hospital and at Cardiology Associates of Princeton was the Cardiologist who would perform them at the facilities available at the Robert Wood Johnson University Hospital (RWJUH) Catheter Lab. I had the pleasure of meeting Dr. Shanahan on Saturday the 27^th of December and we decided on being transferred (by Ambulance) to the RWJUH on the 29^th of December for the procedure..

(D) THE ROBERT WOOD JOHNSON UNIVERSITY HOSPITAL (RWJUH) (1) CATHETERIZATION, ANGIOGRAPHY and (2) TRIPLE BYPASS (OPEN HEART) SURGERY

At this point we were still thinking in terms of a couple of Stents being inserted to relieve a couple of blocked coronary arteries. On the 29 ^th of December I had neither informed anyone in the family nor any of my friends of the impending tests. And expected to have the stents inserted, to recuperate at home and to inform them when it was safe to do so – long after recovery! The reasons for this will become clear soon! But things were about to change drastically – and although I am on the mend physically the progression of changes in perceptions, relationships and the future continues to evolve.

1. Catheterization and angiography reveals a problem that is far more serious than we realized :

(i)     Transfer: I was transferred from the UMC Princeton to the core-2 facility in RWJUH in New Brunswick on the 29^th of December 2015. The mobile Heart Rate Monitors were switched on and the transporting EMS personnel and ambulance from South Jersey used ‘Ambulance Humor’ because they thought it was needed, while the vital signs were constantly monitored even though they stayed stable! At the core-2 facility in RWJUH New Brunswick I was met by a very capable team of Nurses who carried out the standard procedures. They made me comfortable in every way, had me repeat my name, medical history, contacts, etc.., (to ensure that I was alert), recorded my vital signs, replaced the Intravenous (IV) connection in my arm with a new one, etc..

(ii)     What is cardiac catheterization followed by coronary angiography? In the cardiac catheterization procedure a catheter is inserted into the groin or arm and guided along the blood vessels of the torso to the heart and into the Coronary Arteries (21, 22). In the subsequent coronary angiography X-ray opaque dye is released from the terminus of the catheter and X-rays of the arteries and the heart are taken. The distribution of the dye reveals where blockages have occurred in the arteries (21, 22). Needless to say this requires expertise – manual skills and knowledge in Cardiology, both of which Dr. Shanahan was to reveal in spades.

(narrative interrupted).

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(narrative resumed).

(iii)     Catheterization and angiography: On the same evening, of the 29^th of December 2015, I was prepared for catheterization and angiography by Dr. Shanahan’s Colleagues and a team. I was wheeled in on a gurney into a holding room until it was time. After depilation the Electro Cardio Gram (ECG) leads could be attached, sterility ensured and contact made.

(iv)     Catheter Lab: The team was waiting for me in the ‘Catheter Lab’ as it is known. Once again as the two most recent Operating Theaters that I had been in, tended to be packed with equipment, this lab was the opposite of the ones I remembered. Either from the last time I was in one around 40 years ago in Bombay or those from Hollywood. It was brightly lit, but sparse (due to miniaturization of electronics and to ensure sterility concerns?) with a high wattage overhead light and a camera/screen and a computer console next to the operating table. The room was really cold and they covered me with blankets that felt like they had just emerged from an oven (sterility considerations?). The areas for insertion of the catheter were further rinsed and shaved to ensure sterility.

(v)     Shanahan and his team: arrived and I was anesthetized!

(vi)     Shanahan finds a high level of blockage by CAD but a negligible level of cardiomyocyte cell death: I woke up groggily to find Dr. Shanahan pointing to the screen and explaining the extent of the mess! He pointed out that 5 major coronary arteries were massively blocked 95% – 99% with lipid plaque (but only ~2% cardiomyocytes had succumbed to cell death)! I was shocked – not realizing at the time that it could be a number of Risk Factors, rather than my behavior alone, that led to this condition. This was much worse than we had anticipated, with too many arteries involved for the safe insertion of stents. Furthermore, the potential for the deterioration of stents was much higher with greater numbers of stents. The alternative approach of ByPass Surgery was required and he had called the Surgeon for the confirmation of this judgement. It was to be a new Ball Game – called Open Heart Surgery, and I began preparing myself for it! They considered the situation ‘dangerous’ enough as per Dr. Shanahan, to warrant doing the ByPass as soon as the basic information (X-rays, MRIs, Sonograms, Blood work, etc…) could be collected and preparations (for the Operating Theater) completed. All the preparations and preliminary tests were immediately begun.

(vii)     Family notifications? At this point my main concern was whether I should keep this new development from my family. My brother Cyrus Nallaseth who lives in Mumbai, India, has serious health issues of his own, which makes travel hazardous to say the least! He also has primary responsibilities to a young family to consider – his wife and his sons! But should I inform him, I knew all this would not stop him from getting on the first available flight to New York any more than it did from New York to Mumbai when our mother was in the Intensive Care Unit after having had a massive Heart Attack.

(viii)      Dr. Shanahan makes the call: It was finally decided for me when Dr. Shanahan asked whether he could call any family members to let them know. I called my cousin in California (Carl Engineer) and then Cyrus to inform them and still got an earful! Never mind that Cardiologists over the last 10 years, could not have predicted this and until the catheterization and angiography results came in nobody could! And so he was on his way! In fact he had our good friend Mr. Mo Noori immediately drive up from Springfield, Virginia for Moral Support!! Mo, who had been a Radiologist, found me in the corridors while I was waiting to be wheeled into the X-ray suite.

(ix)     Pre Surgery Tests: Throughout the next few days I would go through batteries of tests, procedures and therapies in preparation for Surgery. Blood was drawn for various Pathology Lab Procedures (Lipid Panel, Blood Count, etc…), Doppler Sonograms, ECG, X rays, vital signs repeatedly and regularly taken. There were panels of medications and blood thinners that had to be administered regularly in addition to medications already in use prior to hospitalization and records to be entered. Again as at UMC Princeton, all the Residents, Physicians, Physicians Assistants, Nurses, Nurses Assistants, Technologists and Orderlies were thoroughly empathetic, skilled, dedicated and yet professional at whatever time of day or night that they interacted with me. They are all listed in the acknowledgements at the end of this article.

(x)      Dr. Shanahan met with me: was extremely generous with his time in explaining what was involved in ByPass Surgery and that it had a 98% success rate. We will see why this is an astounding success rate later!

(xi)     Dr. Michael Carlucci the Internal Medicine Practitioner: who assists Dr. George Batsides, the Cardiac Surgeon who would be carrying out the procedure, next stopped by several times to explain his role and procedures and tests that had to be completed before surgery.

2.     Open Heart Surgery – Preparations and Necessary Delays; Being Enveloped with the Healing Support of Care Givers, Family and Friends:

(i)     Dr. George Batsides and his Team stop by: On the 31^st of December Dr. George Batsides and his team came to my room to meet me and explain the procedure, and re-confirmed that ByPass Surgery had a 98% success rate. The prediction is that the patient emerges from the Operating Theater, is held in the Intensive Care Unit (ICU) for 1 day and then in the general cardiac unit (core-2) of the wards for 5 days before being discharged. In fact because of variations in the vital signs (which may have been expected) it took a total of 9 days to be discharged on the 10^th of January 2015 followed by a return after 1 day as a precautionary measure against significant variations of vital signs!

(ii)     The Handbook by Cardiac Coordinators & Nurses Rhonda Sabel and Jen Gopez (60): was extremely useful and outlined Pre and Post Operative Events, Precautions and Preparations in detail for the patient.

(iii)     Dr, Andrew Shanahan and Dr. George Batsides: Perhaps the most important and tangible source of strength and support came from the calm assured manner and concern of both Dr. Shanahan and Dr. Batsides that endured throughout the turmoil that was to follow. As a professional scientist this worked wonders for me!

(iv)     Warmth – circle of Family and Friends: Perhaps another of those most important if intangible sources of strength and support came from the very ones whom I had taken for granted over the years. It is something that as scientists, at least some of us forget, as it is not quantifiable. The presence of Family and Friends – it emanated a glow of warmth! Now I understood another reason beyond precaution, why Dr. Shanahan had asked to notify them. By this time phone calls, emails, cards and appearances from Family members and Life Long Friends (LLF) and/or Long Lost Friends (LLF) from all over the Planet had started pouring in! I had not had a chance to inform most of my colleagues and did not want any of them to feel excluded – or worse unaware of silent cardiac risks that we had uncovered and something of which they may have to be made aware! Although they were always on my mind there were those who had to persevere with penetrating the shell into which I had been placed by my work! Most were confused and shocked to hear the news! I was a good athlete and so they felt I should not have this happening while still others were consumed with worry about Open Heart Surgery as they may not have known of that 98% success rate that Dr. Batsides and Dr. Shanahan had shared. I’ve listed all of them because they all revived me! I had been transported from necessary isolation (and often outright alienation!) for good reason, into a state of warmth, inclusion and belonging! There were many! They were my (1) Nephews Soli Nallaseth, Zahan Nallaseth and my Sister-In-Law Simi Nallaseth, her Mother Sarla Gulati and (2) my cousin Dr. Zenobia Mehta from Bombay (Mumbai) India and daughter of Dr. Meherji P. Mehta, (3) my cousin Anita Jal from Mahableshwar, India (via Melbourne Australia and London, England), (4) my many Cousins and Aunts from London, including Mayerlene Engineer, who is very ill herself, Jessie Dhondy, Perin Martin and Laila and Martin Simpson, Rohin Jal and my cousins Firoza and Farida Cooper and my Aunt Zarine Cooper (whose husband Dr. Rusi Cooper (passed) and Ambassador/Solicitor Nanabhoy ‘Nani’ Palkhivala successfully challenged an stayed a decision by the Prime Minister thus upholding the Indian Constitution in the Supreme Court), and (5) all the Engineers, my cousin Susan and her husband Scott Sherman from California and (6) my Uncle Sarosh Dhondy and Fanny Lopera from Miami FL, (7) and of course Dr.Tehmi Mulla who along with her husband Dr. Dadi Mulla (who has passed) attended Medical School with my father Dr. Soli P. Nallaseth (the first of 3 generations of our family connections) and was deeply concerned! And her son Dr. Adil Mulla my Anesthesiologist/Medical Expert/Life Long Friend (LLF)/Fierce Competitor on the Courts, in the Pools and on the Velodrome or the Road/School Mate, from Warren and Danbury, Connecticut and his daughter Dr. Simone Mulla (JD) of Rutgers University in Newark along with (8) Professor Charles Heckscher my colleague from Rutgers, Squash partner, Coach of the Rutgers Squash Club and neighbor from Princeton and (9) Dr. Rustam Sethna and who came with his wife Katrin Glode-Sethna from Clinton, NJ and my brother’s LLF and my fast friends Mo Noori and Emma Dudang, from Springfield Virginia, (10) Anil Nayar from Miami, FL, a LLF and Squash Mentor and Partner, (11) Libby Case who with her husband both who are also LLF, Squash Students and team mates from Columbia SC from my student days at the University of South Carolina – Libby actually flew up to “bring a glass of water!”, (12) Professor Nawin Mishra who had served as the Chairman of my Dissertation Committee at the University of South Carolina and his wife Punam, called and spoke several times, (13) Cyrus’s Law firm partners Stanley and Maria Wallenstein (Stanley who is not well himself), Piraan Choga and Anil Jethmalani, whom I had got to know over the decades or years, either came or called, (14 )of course decades long friend Sheroy Ranji drove down from Manhatten, NY (15) and finally, Dr. Jeff Ceci with whom I was in Graduate School at USC, Columbia on the phone.

Many of them had emerged instantly and some emerged to recover relationships that had seen years of neglect! I was nestled in a warm glow for once – and not awaiting the Stiletto or the Whisper – with the impending Open Heart Surgery far removed from my thoughts!! It was tonic! I was already grateful, if not for being out of the woods, then certainly for the communion at which I had arrived with those who meant so much to me, and of whom, I had been able to think or think so little over the decades!

(v)     Scientific colleagues, Squash community, Social groups on LinkedIn, Twitter, ResearchGate, and other circles.: I still had to reach out to them! The thought being that disappearing from the Face of the Earth (although unlikely) without reaching out was impolite to say the least – regardless of the background! I had yet to deal with the thought of how easily a struggle to preserve a lifetime of work (again in the Public Interest), could have ended in the garbage if that minor Heart Attack had turned into an irretrievable one either leaving me incapacitated or worse. I had seen a colleague have a Stroke while – we were speaking – as well as the devastation of the after effects and so considered myself fortunate!

(vi)     Adil who is an Anesthesiologist trained at Yale University: had been through a similar life threatening medical situation a few years ago. Professionally he has seen many Open Heart Surgeries and had already inquired about my frame of mind. When I mentioned, that based on my experience (with the effects of the rubbing of enervated trabeculae between the metatarsal and tarsal of the big toe joint in my foot and resection surgery for a pilonidal sinus) I was steeled for the consequences of a motorized surgical saw splitting my sternum, he pointed out that things had changed! The new mesh/net sutures (and superimposed glue) would hold and immobilize the two halves of the sternum and drop the levels of pain that would otherwise come from the ‘rubbing’ of the edges of the enervated trabeculae. Along with the effect of the pain killers and advice by the Nurse’s to hold a pillow firmly to my chest when the inevitable coughing (from fluid filled lungs) or the retching (possibly due to a hyperactive Vagal Plexus (?) began, this turned out to be invaluable and prescient advice!

(vii)     My brother Cyrus Nallaseth was himself: and made me very glad that he had caught that flight to New York despite my exertions! He made sure that the Management at my apartment complex got things, that had been neglected, finally done, made arrangements for a, wonderful Helper at Home, Iris Amaya Castro whom I have got to depend on, arranged for a Visiting Nurse Service, a Rehab Clinic for me after discharge, worked on Health Insurance Extensions, Social Security and other Disability Benefits and generally waited on me hand and foot before and after surgery. I do not think I was ever so glad to see him as shortly after having emerged from Surgery in the Operating Theater and regained consciousness. I found myself in the Intensive Care Unit (ICU) lying on a low slung Gurney craving for a drink of water but unable to speak due to the effects of the anesthesia (60 – 62). I understand that he sent out Daily Bulletins on my condition to our Global Family and Friends.

(viii)     Libby, a LLF arrived from Columbia, SC: after I was moved to the Cardiac Rehab Clinic Libby arrived at a perfect time and spent a few days easing Cyrus’s load both at my apartment and at the Clinic. Libby was being Libby and also waited on me hand and foot! It was good to catch up! While here she called the Social Security Department, worked on Health and Apartment Benefits and set things up so as soon as I came out of the Rehab I could pick up the thread and fill in all the forms on and offline! As of submission the Wheels of Government and Nature are still turning!

(ix)     Mo Noori and Emma Dudang family friends – and a Nurse: who had also helped with my Aunt Firoza Jacobsen when she was in terminal stages of lung cancer in Miami, must have driven up from Springfield, Virginia after work, at least half a dozen times! They kept my brother and I company – as well as running many errands.

(x)     Surgery: Originally, due to the urgency of the situation, surgery was scheduled for the 31^st of December. The exact length of time for the procedure itself would depend on the time taken to complete work on complications and the patient ahead of me in the Operating Theater but the total length of each surgery was estimated at 4 – 5 hours.

(xi)     Unforseen Barriers: However a series of complications in my health arose and surgery had to be postponed several times. It speaks to the professionalism of all the teams involved in leading up to to the Open Heart Surgical procedure that they worked with each other seamlessly! Despite the urgency of the situation, specifically in my thorax, all forward motion to surgery seized when a problem that would complicate the outcome, was detected and only resumed when it was solved! The Cardio-Thoracic Surgical Team stepped back and the appropriate replacement team e.g. Hematologists or Gastroenterologists required to solve the problem stepped up with all the teams working seamlessly with each other. The new team evaluated, quantified, analyzed and solved or classified the problem as non-disruptive, decisions were made and forward progress towards surgery resumed. Although they monitored me closely the urgency for surgery did not induce the slightest panic or rush to action in the Cardiac Team! And although I fully appreciated that the possible consequences of a misstep, might have been my life, this professionalism on their part was not only admirable but also deeply reassuring to me as the patient with a background in science!

(xii)     Problem 1: Enlarged liver and elevated liver enzyme activities. The function of the liver is to de-toxify the bloodstream. To clear persistent toenail fungus I had been on anti-fungizones (Fluconazole, Terbinafine) for around 18 months. These drugs are known to be filtered by the liver which therefore is affected, may have elevated its enzyme activities and size. This enlargement could possibly impede the flow rate of blood through the liver and to the heart creating problems during surgery. The alternative cause for enlargement, of alcohol consumption (less than 1 glass wine/day) was less likely and half a glass of wine per day is actually recommended by the American Heart Association. Half a glass of wine (30 gm) or less actually increases survival of CABG patients by 9% according to the AHA (25). Ultrasound measurements and Doppler Acoustic Sonography of the abdomen showed that the flow rate through the liver was not significantly impeded. We could now move forward. Dr. Pong had known and worried about this problem, we were trying to solve it before the Myocardial Infarction.

(xiii)     Problem 2: I was told that my complexion had become yellowish – did I have jaundice? The bilirubin levels were high. Again this was associated with the malfunctioning liver or gall bladder. However, ultrasound measurements and Doppler Acoustic Sonography of the abdomen showed that the flow rate of blood through the liver was not significantly impeded. It was concluded that a long past infection of Hepatitis B could have spontaneously raised and sustained the levels of bilirubin but it was not an impediment to surgery. We could now move forward.

(xiv)     Problem 3: Hemoglobin and the blood count was low. I was given 2 units of blood, the count was restored and we could now move forward.

(xv)     Problem 4: I had always had routine outbreaks of gout caused by crystals of uric acid deposited in joints, possibly breaking loose spontaneously and causing inflammation. Often, as on that occasion, for no apparent reason. Loose crystals could complicate surgery! A quick determination of uric acid levels showed only ~15% elevation. We could now move ahead.

(xvi)     Problem 5: the vital signs (blood pressure, heart rate and temperature) fluctuated fairly widely. It was decided that this was either a consequence of the Heart Attack or not serious enough to hold an urgent procedure where they would be stabilized manually and we could now move forward.

(xvii)     Still more preparation: involved identifying potential veins in the leg which were mapped for Endoscopy Vein Harvesting for CABG in the Endoscopy Lab (60 – 64).

(xviii)     Finally I was wheeled into the Pre Operating Theater: on the morning of the 2^nd of January the Orderly wheeled the Gurney I was on into the Pre surgery Preparation Room. Along the way he lightened up the atmosphere by informing me that I had a high bar to match. Someone had gone through Open Heart Surgery and run a marathon only 10 days later!! Well I am not sure what to say – and neither could Dr. Shanahan! Although the whole ByPass Surgical experience was much less painful, if much more weakening than I anticipated (10 days after surgery I could barely sustain a conversation for 10 minutes without getting winded) I cannot imagine having walked let alone running a marathon 10 days after surgery!

3.     Open Heart Surgery – Pre Operating Theater Preparations and the Operating Theater on 01/02/2015:

(i)     In going through the insurance forms and Hospital charges the broad categories of procedures in the Operating Theater were identified and led to the list presented below (SIB -4). They are listed below in the narrative resumed in the Operating Theater

(There were approximately 25 Pre- and Post- Surgery Pathology Tests for Markers, in addition to Electrocardiographs (ECG), Sonograms, X-rays, Doppler and other tests resulting in the conclusion of “ACUTE MI SUBNNOCARDIAL INFARCT INIT EDC” and “RECOVERY” many of them given/measured multiple times/24 hour period. They reflected the extreme care given to me as the patient).

(ii)     The various types of Heart Surgery are well documented by NIH and by RWJUH (60 – 64). I was to be subjected to Pump Assisted Coronary Artery Bypass Grafting (CABG) pronounced like the vegetable or ‘cabbage’, i.e. the Heart is replaced by an artificial pump. As I would be unconscious during the procedure and so unaware of the steps, this is the description of CABG from NHLBI (NIH) website:

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The Operating Theater:

(iii)     The nurses depilated the chest, checked the IV and injected a blood thinner. A local anesthetic was administered and the catheter with sensors inserted through the neck into my heart to monitor its vital signs in real time. The steps to be taken by the Cardiac Surgeon, some, while I was under anesthesia:

(a) Anesthesia CABG with Pump

(b) Insertion catheter, Artery

(c) Insert/Place Heart Catheter

(d) Echo Transeosophageal

(e) Doppler Echo Exam, Heart

(f) Doppler Color Flow Add-On

(iv)     The Operating Theater looked like a more (or better?) equipped version of the catheter/angiography lab. However, compared either to the version in the Movies or the ones I remember in India when I was the patient and operated on by an Uncle, Dr. Meherji P. Mehta, this one was sparse. Possibly to preserve sterility. Dr. Mehta was a pioneering Cardiac Surgeon who performed the 4^th Ventricular Septum Reconstruction as well as some of the first Heart Transplants in the History of Cardiac Surgery at the K.E.M. Hospital in Mumbai (65, 66). He was also a contemporary of the renowned Pioneer of Cardiac Surgery Dr. Michael DeBakey with whom he exchanged Surgical visits. Although Dr. Mehta secured his F.R.C.S. degree in the UK his specialized training in Cardiothoracic Surgery was received at the Christian Medical Center in Vellore (C.M.C.V.) directed by Dr. Reeve Betts. This was one of the 3 Major Cardiac Centers established in India by British Surgeons who had mastered their craft in the Theater of the North African Desert in the Second World War (65, 66). Ironically Dr. Mehta, like my father (his step brother) Dr. Soli P. Nallaseth succumbed to Heart Attacks or Ventricular Fibrillations in their mid to late fifties. All of us in our immediate and several others in our more distant family either succumbed to or had Heart Attacks or Fibrillations when relatively young. However, in each case overwhelming additional factors complicated any simple interpretation of family history or a genetic cause (65, 66).

(v)     My brother was designated as the responsible relative to whom reports would be delivered and along with Mo waited outside the Operating Theater over the 4-5 hours of surgery.

(vi)     Dr. Batsides reassured me that his assistants ‘really knew their work’! But I had no doubt especially since everything the Surgical Team had done up till then was convincingly efficient, diligent and professional. I was as relaxed and accepting, as one can be under those circumstances, for the simple reason that I would have liked to live a little longer!

(vii)     I remember feeling some blood trickling down my neck from the ‘In Heart ‘ catheter and their fixing it in short order with a few stiches.

(viii)     Shortly after this the anesthetic was administered, I blacked out and assume that the CABG procedure described in (SIB-4) from the NHLBI (NIH) website began.

(ix)     I awoke on a low slung gurney in a line of gurneys in what presumably was the Intensive Care Unit (ICU). It was painted bright white with Nurses, Assistant Nurses. Technologists in white and urgent, purposeful but unhurried movements. There is a good description in NHLB – NIH outline of CABG in (SIB-4).

(x)     My throat was parched and when I tried speaking, no sound emerged, due to the effect of the anesthetics! So I could not get the drink of water that I desperately needed.

(xi)     My brother Cyrus was allowed into the ICU – I had that water soon. I don’t think I’ve ever been so glad to see him! And soon enough realized it was going to be a tough few days to normalcy.

(xii)     I was re-attached to a mobile Cardiac Monitor and intravenous IV feed and moved to the core-2 facility (Cardiac Wards) the next day.

(xiii)     The impression of the whole CABG process and its aftermath that lingers in my mind is not one of excruciating pain, but certainly one of labored attempts to move, resulting in acute discomfort, even sitting was difficult and conversations led to being easily winded within minutes! This low consequence was probably due to the excellent surgery and the thorough immobilization of the incision along the sternum, the pain killers and nursing all of which were excellent! Food did not seem at all appetizing – partly because of the fear of unleashing a ‘retching’ episode. One attempt, in that first 10 day period, at a Walker Assisted walk around the core-2 ward sent my blood pressure soaring! So walks were suspended!

(xiv)     Here too the Nurses, Nursing Assistants and Technical Staff taught me little tricks like building up my strength by sitting, rather than the more easily done, lying in the bed. One of the pieces of equipment used to ease the congestion in the lungs and keep them functional was the Spirometer – breathing into it to elevate the indicator, maximally without overshooting an easily overshot mark – 10x/day. The Nurses were insistent but in the only resistance I gave them, I found the Spirometer to be a waste of time – needless to say I was wrong!

(xv)     Dr. Amy Tilara, among others from Dr. Batsides group, checked my condition every day before and after surgery, e.g. making notes on the records of the vital signs. Dr. Tilara was also the ‘Enforcer of Spirometer Use’ and fairly dogged in extracting an accounting! She was also the one to deliver the message related to the 2^nd discharge after I had been brought back from the Foothill Acres Rehab Center when the vital signs fluctuated again.

(xvi)     I was looked after and monitored closely in core-2, from the recording of vital signs to any of the ablutions and to the slightest need all of which were responded to when the buzzer brought them to my bedside. This besides their doing such things as recording ECGs with portable machines, administering medications at regular intervals at all times of the day and night.

(xvii)     I have never felt so dependent! Something that is anathema to me! Probably because of my professional experience!

(xviii)     The vital signs, particularly my temperature and blood pressure fluctuated sufficiently to cause some concern for the next 2 weeks. But considering the magnitude of the impact that the CABG procedure had to have on the body perhaps this was not entirely surprising.

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(E) CARDIAC REHAB AT THE FOOTHILL ACRES REHABILITATION AND NURSING CENTER:

(i) Discharge from RWJUH core-2 on the 10^th of January 2015 was administered by Dr. Leonard Lee, who was the Chief of Cardiac Surgery, and stopped by to check the scar and by Nurse Kelly Mayer-Delgado. Nurse Mayer-Delgado had spent time with and shown me several ways of managing the everyday problems that follow Bypass Surgery throughout my stay in the core-2 facility. She got me to stand for Dr. Lee without wobbling too much!

(ii) Dr. Lee caught sight of my Squash Bag (now serving as a garment bag) and that led to an exchange of some pleasantries about our mutual interests in the game, a friend and fellow Coach Geoff Mitchell from a Club (the Chatham Club) at which we had spent many years playing Squash (and I sometimes still do).

(iii) I was then prepared for the ambulance and transported to the Foothill Acres Rehab Clinic (FARC) for cardiac rehabilitation.

(iv) Little did I know that I would be returning to RWJUH the next day. The vital signs (blood pressure, heart rate, pulse and temperature) were high or fluctuated and a vigilant Nurse and Physician wanted the immediate results of a possible infection with microbial assays that were available at RWJUH but not at FARC.

(v) I was returned to the Emergency Room at RWJUH, with the vital signs elevated. Then tested for infections, other sources of problems, and while the vital signs stayed elevated.

(vi)I was kept under observation overnight. After Dr. Batsides’ and his Staff concluded this was normal given the magnitude of the impact that the surgical procedure would have had Dr. Tilara communicated the message and I was returned to the FARC Rehab Center the next day.

(vii)The Foothill Acres Rehab Center as its name implies imposed a regimen of a good diet, monitoring of the vital signs, good regimens for medications, therapies and physiotherapy. Which may explain the rapid recovery of patients.

(viii) One of my Room Mates at Foothills was an Engineer – Vincent Barone. Our conversations were entertaining.

(ix) On the 4^th of February 2015 I had a long overdue follow-up visit with Dr. Batside’s Colleague and the Cardiothoracic Surgery Clinical Coordinator Rhonda Sabel RN.C.BSN. and was given permission for Discharge from the Rehab Clinic.

(x)By now I had started using my laptop and learned the sad news that my good friend Princeton Squash Coach Bob Callahan had finally fallen to the glioblastoma that he had resisted for 3 years on the 27^th of January 2015! More than twice the mean time that other patients with this dread disease survive!

(xi) Players from the Rutgers Squash Club organized a memorial posting for Bob on the online journal Daily Squash Report and the social medium LinkedIn.

(xii) In thinking of the events of that past month I realized that my colleagues, mentors and friends in Squash at all the courts, in Science, at the New York Academy of Sciences, the Society for Developmental Biology, other Universities, Institutions, on Social Media like LinkedIn and ResearchGate among other places would want to know of the recent events and its strange biomedical contradictions! And so I sent out emails or posted the news on Social Sites and received nearly 300 deeply concerned, warm, supportive and encouraging replies!

(xiii) By the 30^th of January 2015 I had been walking without a walker!!

(xiv) By the middle of that week of 4th of February 2015 I was climbing 78 steps on the FARC staircase which was equal to twice the numbers of stairs present at home, in addition to Physiotherapy administered by the expert Therapists of Foothills Acre Rehab Clinic.

(xv )By the end of that week, 6^th of February 2015 I thanked the entire staff and personnel who had got me back up on my feet again and left. Iris brought me home.

(xvi) It was clean – Cyrus, Iris and Libby had done all the work!!

(xvii) I was still too unsteady to do much.

(xviii) On the 28^th of February I could finally drive and make the overdue follow-up visit with Cardiologist Dr. Shanahan.

(xix) He put me through the necessary Stress Test on the 13^th of March 2015.

(xx) I was cleared for cardiac physiotherapy at the University Medical Center of Princeton and made arrangements – but Squash and the Apartment Gym were  excluded for 6 months.

(xxi) I have now been writing regularly since 3.3.2015.

(narrative interrupted).

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(narrative resumed).

(F)  A series of questions and issues related to my heart attack or MI arise that are addressed below.

• As discussed the two types of traumatic cardiac pathologies resulting from either the deprivation or the complete cutoff of the supplies of blood flow and so O₂ by plaques or fibrillation (fluttering heart muscles), respectively cause Myocardial Infarctions (Heart Attacks) and Sudden Cardiac Arrest (SCA) or Sudden Death (SD) (20, 23 – 27, 30). The Risk Factors for these 2 types of pathologies have also been discussed briefly but are dealt with in greater detail in the supplementary information box (SIB-7) and in even greater detail by multiple health agencies (8 – 27). As is clear from the above references cardiac diseases are considered to be multifactorial (genetic, environmental, behavioral, among other factors). It is useful to now specifically focus on the 5 principle elements of the cardiac event of 12.25.2914      (1) Risk Factors and the role of exercise in modifying or ameliorating them,(2) Squash ameliorates the Risk Factors as shown by results from recent studies that are in depth and so subsume contradicting results of older studies,(3) New research results support the interpretation that the intense competitive and exercise routine that I maintained in India, (high level overtraining) delivered conditioning that was at least partially retained in the US until 2006 and 2007,(4) This conditioning likely delayed the ongoing coronary artery disease (CAD) and the ongoing coronary heart disease (CHD), (5) Ameliorated the impact of a Heart Attack by preconditioning (IPC) cardiomyocytes.

The relevant literature, albeit selected, that will be drawn on, is listed in the (SIB-7). However a significantly more detailed version of the discussion of these events and the relevant literature on Sports Physiology and Clinical implications will be submitted to the appropriate Journal (1).

• Salient and relevant features in the reconstruction of events from diagnosis and intervention to recovery, from: questions, medical reports and extrapolations of the literature:

 To summarize the details, the salient features of the cardiac events in my thorax culminating in the Coronary Artery Bypass Graft (CABG) Surgery and into ongoing recovery, as determined by (i) Cardiologist Dr. Andrew Shanahan, (ii) Cardiac Surgeon Dr. George Batsides, (iii) their teams, (iv) extrapolated from the literature, (v) those factors that remain unknown are enumerated as 1-14 below. The questions raised and possible reasons for survival are also considered.

(1)     Need for Oxygen: As it is indispensable as a terminal terminal e^-1 acceptor required for generating molecules of ATP, the high energy vehicle which is required for most cellular functions, Oxygen is of fundamental importance to the survival of the vast majority of living organisms. The importance of Oxygen to the function and survival of cardiomyocytes and the heart has already been established in this article (SIB – 1).

(2)     Sequence of events leading to, and reasons for, the CAD and MI: As mentioned, in the 10 years from around 2005 to 2014, I had multiple chest spasms, underwent multiple tests of increasing rigor, for detecting cardiac malfunction, and in more than one institution. All of which had failed to implicate cardiac malfunction as the cause of my chest pains. Although there are several possible reasons for this interpretation: (a) the accumulated plaque in arteries (due to CAD), known to occur over decades, was likely already present during those Stress Tests but went undetected, (b) detection of cardiac mal-function or blood flow and so O₂ supply in these Stress (and other) Tests are revealed by cardiac electrical (Electrocardiographs , ECG) perturbations of the discharge by cardiomyocytes which is caused by exercise dependent hypoxia (O₂ deficits) and detected by (ECGs). These cardiomyocytes were not perturbed and so failed to reveal cardiac mal-function, (c) they were probably not perturbed because the cardiomyocytes were hypoxia tolerant, due to their overtraining based ischemic preconditioning (IPC) resulting from training for Squash, (d) this inference was supported by the necessity for having to elevate the Treadmill Settings (stress) 3x above normal settings for Stress Tests before hypoxia driven stress on the ECG, even registered, (e) this despite the likely hypoxia caused by the plaque ridden vessels (CAD) in addition to that caused by the Stress Tests, (f) Stress Tests are among those widely applied as a first line of investigation, but often may fail to detect cardiac malfunctions, as may have been so in my case, (g) however this explanation is the unlikely choice between known effects (IPC, 3x elevation of Treadmill settings) and a hypothetical premise (rate of failure of stress tests), (h) or alternatively significant blockage of coronary arteries (by CAD) and the resultant hypoxia may have set in relatively recently and rapidly (after the 30^th of April 2010, which was the date of the most recent comprehensive cardiac tests) and (i) this explanation is also unlikely as an asintotic elevation of CAD is not commonly known.

(3)     Time course for plaque formation: The period of time that the plaque dramatically reduced or blocked, blood flow in 5 major coronary arteries, and so the Oxygen that they delivered to the cardiac tissues to induce hypoxia in cardiomyocytes, cannot be determined. The rate of deposition of plaques to attain a final blockage of 95% – 99% in 5 major coronary arteries is unknown. This level ranged from near complete 95% (hypoxia) and approached complete deprivation 99% (anoxia) of blood flow and oxygen delivery to cardiomyocytes, (personal communication from Dr. Shanahan and his Medical Report) is a condition which is likely to be lethal within 5 minutes.

(4)     How many cardiomyocytes succumbed? Yet only ~2% of cardiomyocytes were irreversibly dead as determined by Acoustic measurements during catheterization and angiography (personal communication by the performing Cardiologist Dr. Andrew J. Shanahan and Nurse Rhonda Sabel). They were presumably lost to apoptosis caused by anoxic conditions.

(5)     Why was there such a large disparity (~ 50x) between blockage of coronary arteries by plaques and cardiomyocyte cell death? Why were only ~2% of cardiomyocytes lost to cell death when the blockage of 5 major coronary (blood) vessels amounted to 95% – 99% with its corresponding reduction of blood, and so Oxygen, supplies? Although based on Retrospective Birth Dating (RBD) of cardiomyocytes, ~95.6% of cardiomyocytes could be expected to be resistant to hypoxia due to overtraining and IPC they would not be resistant to anoxia which is lethal within 5 minutes. This is shown experimentally as well as by the results of Atrial or Ventricular Fibrillations (fluttering heart muscles leading to a cutoff of blood and O₂). It is possible that the ~2% of cardiomyocytes that succumbed were located in a cardiac segment that was anoxic.

(6)     What is the window of time between plaque deposition to complete arterial blockage and new blood vessel formation to relieve the pressures of hypoxia but not anoxia? It is known that new coronary blood vessel formation is induced as a compensatory response to hypoxia resulting from the blockage of coronary arteries by plaques through processes called angiogenesis or vasculogenesis (37). Their growth is stimulated by vasculogenesis endothelial growth factor (VEGF) and GATA nucleotide sequence binding protein, binds nucleotides (GATA 1-6), among other factors (37). However, fragments of plaques are broken off walls of blood vessels, either form dangerous and circulating clots or travel to new sites, where they are deposited and form nucleation foci for new deposits at rapid rates (SIB-4, NHLB(NIH). We neither know how quickly the plaque was deposited to block the blood vessels nor how quickly induction and new blood vessel formation occurred. But there must have been a window of time between, plaque deposition upto near complete blockage and the formation of new blood vessels vessel induced by VEGF, in which hypoxia had not yet progressed to anoxia. The length of this window of time that was sufficient to allow cardiomyocytes to survive is unknowable. However ~2% of cardiomyocytes did succumb to cell death and so there is evidence for this window having closed. This cell death (~2% cardiomyocytes) was either due to their location in a cardiac segment that was anoxic or due to an incomplete transfer of hypoxia (apoptosis) resistance from hypoxia resistant nuclei to newly born cardiomyocytes as is shown to occur in myonuclei (67). These new cardiomyocytes were likely born in the ~7 years after 2006/2007 the last 2 years of my low level overtraining for Squash in the US.

(7) (a)  How much hypoxia can cardiomyocytes tolerate and for how long do they do so in order to be able to resist cell death (apoptosis)? (b) How much anoxia can cardiomyocytes tolerate and for how long to be able to resist cell death (apoptosis)? The answer to both is unknowable without experiments. But the answer to (a) is complicated while the answer to (b) is the 5 minute period (maximally) and 10 minutes (survival with irreparable cardiac and neuronal damage) that emerges from Sudden Cardiac Arrest (SCA) or Sudden Cardiac Death (SCD) reports in the literature (SIB- 4, NHLB(NIH).

(8)     How long and how much did ischemic preconditioning (IPC) contributed to the observed disparity between coronary artery blockage (95-99%) and cardiomyocyte cell death (~2%)? A further complication arises from applying interpretations of results from experimental mammalian systems (mouse and rat) to humans. In rodents it has been shown that an initial and transient application of hypoxia (e.g. for 20 minutes) induces a state of tolerance (resistance) to subsequent prolonged challenges of hypoxia even 72 hours after transient exposure. This is known as ischemic pre-conditioning (IPC) and molecules either encoded by genes such as Akt, JAK-STAT, Bcl2, VEGF, GATA 1-6 BF, p38 kinase, HIF1, EPAS1, or hormones Estrogen or the signaling molecule NOX₂, and the anti-inflammatory drug Sulindac all contribute to this effect through known pathways and mechanisms (36 – 51). Although overtraining dependent ischemic preconditioning (IPC) pre-conditioning in Squash probably facilitated survival of cardiomyocytes during the Heart Attack (MI) ~ 2% cardiomyocytes succumbed probably to anoxia. Some questions that follow. What was the distribution of blocked and new coronary (blood) vessels over the heart and did it supply the segment of the cardiac tissue spanning those ~2% cardiomyocytes that succumbed? What was the contribution of IPC in the blocked and supplied cardiac segments of cardiomyocytes? How long after this window of time between complete blockage and supply of new vascular vessels to populations of cardiomyocytes closed did they survive? These questions are unanswerable!

(9)     How many Cardiomyocytes were born after low level overtraining had ceased in 2006/2007? And were they resistant to hypoxia and apoptosis? Jonas Frisén, and his colleagues have innovated a method called retrospective birth dating (RBD) which measures the replicative loss of atmospheric residual ¹⁴C radioisotope with long half-life of 5,730±40 years, released from surface atomic tests and incorporated into our genomic DNA, by alterrations in ¹⁴C:¹²C ratios of tissues (58, 59). They used RBD to show that approximately 50% of cardiomyocytes were replaced in a human lifetime (58, 59). Based on this estimate and an average Life Span of 80 years the calculated number of newly formed cardiomyocytes in my heart since 2006/2007 (~7 years) is ~4.4% new cells. Can this number be used to calculate the numbers of cardiomyocytes that were ‘born’ after the cessation of low intensity overtraining (strenuous workouts) and hypoxic conditioning? These new cardiomyocytes (~4.4%) were not exposed to low intensity overtraining and despite predictions (67) may not have been equivalent to the ~95.6% of cardiomyocytes that were exposed to low intensity overtraining 7 years ago (in previous workouts) and so may not be preconditioned by IPC to resist hypoxia (67). Alternatively, either the transfer of resistance from the old hypoxia/apoptosis resistant templates was only partially complete in ~2% of cardiomyocytes, or they were resident in a segment of cardiac segment that was only partially vascularized nearly devoid of blood flow and so O₂ thus becaming nearly completely anoxic. These questions are unanswerable.

(10)     Could high intensity overtraining for Squash which is a high intensity sport (METs index = 6 – 12 cals/kg/hr) in India 38 years ago (since 1976) have conferred IPC that was retained and so contributed to the survival of my cardiomyocytes in 2014? Could hypoxia resistance result from low intensity overtraining in the US (upto 2006/2007) and have lasted for ~7 years after nearly detraining (2006/2007 to 2014)? From experimental work done in rats it is known that skeletal muscle myocytes following strenuous training (overtraining) gain in numbers and sizes of myonuclei which results in hypoxia (and apoptosis) resistance (67). This increase in numbers and sizes of myonuclei correlates with hypoxia resistance and is retained after at least 3 months of detraining (67). After detraining these trained myonuclei remain resistant to hypoxia and apoptosis, and may serve as templates for the synthesis of new hypoxia and apoptosis resistant nuclei and are likely to extend conditioning into old age (67). This last observation is common knowledge among athletes! Based on several physical and physiological parameters of estimation (4), I had overtrained for Squash at a significantly higher intensity (or high intensity overtraining) more than 38 years ago in India until having arrived in the US in 1976. Based on the calculations in question 9, this would yield 23.8% of newly born cardiomyocytes since 1976 in the US, that were not exposed to the same high intensity overtraining. The intensity of overtraining in the US varied from low level overtraining to detraining (none) for Squash tournaments which would leave at least 23.8% of newly born cardiomyocytes either resistant or sensitive to hypoxia and apoptosis. This depends on whether this level of overtraining in the US was sufficient to induce hypoxia/apoptosis resistance. If sufficient does it explain the retention of hypoxia resistant conditioning over the 7-8 years since 2006/2007 when even the lower (US based) level of overtraining ceased? And are the ~2% cardiomyocytes that were not resistant among the calculated cardiomyocytes (~4.4%) that were ‘born’ in this period? Were these ~2% cardiomyocytes either (i) not exposed to sufficient overtraining and so endowed with low levels of hypoxia resistance or (ii) actually detrained or (iii) had they failed to acquire any resistance from hypoxia and apoptosis resistant nuclear templates or (iv) were they resident in a segment of cardiac tissue that was devoid of blood flow and O₂ and so completely anoxic thus so succumbing to cell death? These are unanswerable questions.

(11)     Can cardiomyocytes survive anoxia? How many cardiomyocytes must be lost to apoptotic death to result in Sudden Cardiac Arrest (SCA) or Sudden Death (SD) fatality rather than Myocardial Infarction (MI) or Heart Attack ?

Cardiomyocytes may survive anoxia for more than 5 minutes but the damage is irreparable and after 10 minutes anoxia is invariably lethal. Finally there is a threshold of cardiomyocyte cell death that must be attained for the Myocardial Infarction to become irreversible. Why and What is that number? In Sudden Death (SD) or Sudden Cardiac Arrest (SCA) syndromes it is known that the entire Atrium or Ventricle fibrillates (flutters due to uncoordinated electrical discharges required for contraction) and so blood supply and Oxygen are cut-off. And lethality results in as little as 5 minutes This shows that inactivity of either of these 2 chambers is sufficient to prove fatal.

(narrative interrupted).

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narrative resumed:

SUMMARY:

1. In other words, the literature supports the inference that, my competitive days in the game of Squash Rackets and high intensity overtraining for it, had delayed the deposition of plaques by CAD so it only gradually rose to 95-99%/CA/5xCA and conferred hypoxia and apoptosis resistance due to IPC that was retained on ~98% of my cardiomyocytes. When this near complete blockage and other Risk Factors (professional pressures, family background, etc..) finally precipitated the MI the extent of cell death and so cardiac damage was limited to ~2% cardiomyocytes. Thus enabling the Cardiologists, Cardiac Surgeons and their teams to save my life!
2. Although we cannot prove it for the MI affecting my heart, the current literature establishes that overtraining in high intensity sports like Squash (with an underestimated METs index of 6 – 12 cals/kg/hr), elevates the level of general and cardiac conditioning, both slowing down and diminishing the risk of Coronary Artery Disease (CAD) or Coronary Heart Disease (CHD) by 22% – 40% while also allowing cardiomyocytes to resist oxygen deprivation (hypoxia) from constricted coronary arteries due to ischemic preconditioning or IPC (SIB-7).
3. As far as the Open Heart Surgery goes, there were mixed reactions as is to be expected. Although there was post-surgical pain, some unpredictable vacillations of vital signs, an acute weakness that permeated my being, including a temporary 30 lb loss of weight (which was much needed), for a period from a week to a month, the overall impression I have is one in which all of these factors were of much lower intensity than expected for such a drastic procedure. I have changed my life style drastically at least partly in gratitude for all that was done by these professionals to save my life!
4. We begin with the central players in all this! Despite the conceptual and technical complexities of the procedures involved, namely the catheterization and angiography done by Dr. Andrew Shanahan and the coronary artery bypass graft (CABG) done by Dr. George Batsides and their respective teams, they met the requirements of the daunting success rate of 98% because their work was carried out flawlessly. This, despite the various pathological obstacles that arose and the impending urgency of the circumstances in my thorax! The CABG procedure involved surgically opening a chamber, the thorax, which has remained hermetically sealed, for good reason, across Vertebrate Evolution. This was followed by their Bypass work on the heart, which as robust and active an organ as it is, is still susceptible to all manner of electrical and other failings. All this was done while I as the patient was on pump assisted breathing and circulation! And finally there was the required resealing of the thorax without allowing a leak to develop (the consequences of which are amply demonstrated by the associated pathologies). All this is done with the high success rate of 98% – which is unbelievable for those of us who are Experimental Biologists! All the Physicians, Surgeons, Nurses, Technological Staff were always completely professional, dedicated and technically skilled and yet remained kind, warm and deeply concerned about my wellbeing! There was never any panic on their part despite the unpredictable pathological problems that arose under highly urgent circumstances – in which the possibility of fatality always loomed! And this only led to further reassurance for me as the patient!
5. The entire sequence of pre-events and events related to the Myocardial Infarction (heart Attack) that I had, from its beginnings on the 25^th of December 2014 to the present day and the time of submission of the manuscript (9^th May 2015) was played out flawlessly by the Biomedical Professionals, Physicians, Surgeons, Nurses, Technological Staff, Family and Friends with myself as the beneficiary. Which is probably why I am alive! They are all listed in the copied Portable Document Format (or pdf) file entitled ACKNOWLEDGEMENTS.
6. My family and friends, some with whom I had lost touch, simply leapt to my rescue when the news got out! They were on the phone or appeared by my hospital bedside dropping urgent matters in their own lives, and in some cases risking their own healths with long and arduous journeys, to do so. None more so than my brother Cyrus Nallaseth who despite his own dangerous health circumstances, caught the first available flight out of Mumbai (Bombay) India to be by my bedside! This alone gives me the impetus to not waste their time and effort! I am still soaking up the enormous sense of having been sheltered and so remaining alive!
7. My fellow patients and I at the Cardiac Pulmonary Rehab Facility at UMCPrinceton at Plainsboro cannot overemphasize the importance of systematically surveying the usefulness of catheterization and angiography as opposed to non-invasive Stress Tests and Radioisotopic or Acoustic tests to detect certain ‘silent’ cardiac pathologies so as to establish their true frequency. Perhaps in conjunction with the development of a new more reliable method. This is especially so with athletes or those who have overtrained at one time, so as to acquire IPC, which is likely retained even if they have subsequently detrained. This as we saw since the cardiac muscles are likely to have retained the capacity of hypoxia resistance and so are not stressed by standard Stress tests and would mask cardiac pathologies. In my case, despite chest spasms, and the likely presence of advanced CAD the other non-invasive tests had failed to detect effects of cardiac or coronary artery plaques over a period of a decade. So cardiac involvement was inaccurately if understandably excluded with a 95% confidence a short 4.5 years ahead of the MI incidence.
8. So while the hypoxia resistance of the cardiomyocytes prevented the various cardiac Stress Tests from stressing the heart sufficiently to allow detection of CHD/CAD, for 10 years, when the Myocardial Infarction (Heart Attack) finally occurred, ~98% of the cardiomyocytes could resist prolonged hypoxia and I likely escaped a major and possibly lethal, attack! As was inferred those ~2% cardiomyocytes that succumbed to cell death during or prior to the MI were either anoxic for more than 5 minutes or less likely not resistant to hypoxia due to the incomplete transfer of hypoxia resistance from the resistant templates (page 38 – 39 of narrative, SIB-7). The former parallels events in Sudden Death or in Sudden Cardiac Arrest (induced by Atrial or Ventricular Fibrillation, (SIB-7). The latter could occur when cardiomyonuclei may not have acquired hypoxia (and apoptosis) resistance from the resistant template nuclei of overtrained cardiomyonuclei (SIB-7).
9. Although invasive tests (catheterization and angiography) are more revealing and reliable than non-invasive tests (Stress, Acoustic, ECG, Tests etc..) in diagnosing Cardiac mal-function, they bring greater associated risks to the process. A need exists for the development of an alternative method of diagnosis which incorporates all the advantages without the risks associated with these 2 methods. Of necessity preceded by a re-evaluation of the methods for detection of all types of silent diseases affecting the Cardiac system. For example considering development of various Tomography approaches e.g. Multi Spectral Optoacoustic Tomography (MSOT) without catheterization (97, 98)
10. An attempt has also been made to come to terms with perhaps an insidious process that is still underway – somewhere in the back of my mind. This includes, the many communities in any life – family, friends, medical, professional and social networks. Those who were either at one with me, or leapt to my rescue, and also included adversaries or onlookers who seemed to be genuinely concerned. Possibly as the Specter of Mortality is always intriguing?
11. Of course work that is unfinished due to unavoidable circumstances that were alluded to earlier, and the transience of life were the compelling, if sub conscious, forces over the past ~40 years that also occupied my thoughts immediately after the Myocardial Infarction episode. I am now moving as quickly as possible to put this and other unfinished work into the literature!
12. Last but not the least I simply cannot but marvel at the magnificent social processes that were at play in all the Biomedical facilities and which represented the most redeeming characteristics of Humankind! It left me as the beneficiary with a new lease on Life! I was, as someone unknown, to the Biomedical communities in those hospitals, carried in from the street, and yet in effect made as one of their own! They showed remarkable concern, kindness, warmth, empathy, generosity, graciousness, and yet retained all the skill, dedication and the professionalism that was so important to the recovery of the patient – myself (99)! And so they will remain among those to whom I owe my life!

Addendum added by FSN

 Something that might have contributed to my escape from certain death by MI and by the minimal odds of 48:1 requires emphasis! In the paper by Northcote et al (83), which is actually often misquoted on Google as Squash Causing Heart Attacks), of 60 deaths on the Squash Court, postmortems showed that at least 48 players had advanced CAD/CHD. They were ~20 or 30 years younger than I, could not possibly have had a greater extent of CAD than I did (95%-99%/CAx 5CA) and were certainly in  better condition than I was at age 62. So why did I live – at 48:1 if not greater odds? The answer may be that I had stopped playing at anywhere near the intensity (maximal METs index) as hard as I did, ~7 years earlier. Although I almost certainly had IPC preconditioned cadiomyocytes they may not be able to survive this combination of maximal intensity and CAD which is the reason for the reported fatalities on the court (83)! And since I did not get anywhere near that level on the court after 2007, I survived!​

ACKNOWLEDGEMENTS:

I cannot express enough gratitude for the innumerable and different ways in which all of those listed below contributed to saving my life. As well as in making it possible for me to eventually emerge from Open Heart Surgery while remaining as comfortable as was possible given the circumstances! Should I have inadvertently left out a name please accept my sincerest apology. Ferez

See additional acknowledgemnents at the following link: Acknowledgements.5.9.2015.pdf

FSN would like to acknowledge the editorial assistance of Dr. Stephen J. Williams, Ph.D.

REFERENCES :

(1) Nallaseth, FS. Overtraining Even Followed by Prolonged Detraining May Delay the Progression of Coronary Artery Disease (CAD), Prevent Detection But Promote Survival, During Resultant Myocardial Infarctions – A Review. To Be Submitted to ESSR (2015)

(2) National Institutes of Mental Health, http://www.nimh.nih.gov/health/statistics/prevalence/index.shtml

(3a) Popova, M. Darwin’s Battle With Anxiety. brain picking’s newsletter http://www.brainpickings.org/index.php/2014/08/28/darwin-anxiety/ (2014)

(3b) Via Peter Shimon and the Darwin Evolutionary Medicine Group on LinkedIn https://www.linkedin.com/grp/post/4307197-5910792655075315712?trk=groups-post-b-title).

(4) Nallaseth, FS.Training Regimen to be Used as a Model for the (partial schedule of Off Court workout). http://www.eden.rutgers.edu/~rusquash/columns/RU_squash_workout.pdf

http://www.forbes.com/2003/10/01/cx_ns_1001feat.html

(5) Forbes magazine reveals: The healthiest sport in the world, Health and Fitness Club, Fsp Health, 01.11.2013

http://healthandfitnessclub.co.za/articles/sport/forbes-magazine-reveals-the-healthiest-sport-in-the-world-197.html

(6) Top Ten Healthiest Sports (see following pdf Table): ForbesTable-SqHealthiestSp.c012005squ Forbes Magazine

(7) Barrington, J. Barrington On Squash – The definitive coaching book by a world champion, 2^nd Edition, Publisher Pan Books, Cavaye Place,     London, SW10 9PG (ISBN-0 330 24670 4) (1976), http://www.amazon.com/s/ref=nb_sb_noss?url=search-alias%3Dstripbooks&field-keywords=Barrington+On+Squash

(8) Centers for Disease Control and Prevention (CDC),

http://www.cdc.gov/heartdisease/risk_factors.htm

(9) U.S. National Library of Medicine,

http://www.nlm.nih.gov/medlineplus/ency/patientinstructions/000106.htm

(10) New York State Department of Health, https://www.health.ny.gov/diseases/cardiovascular/heart_disease/risk_factors.htm

(11) The National Heart, Lung and Blood Institute of the National Institutes of Health (NIH), http://www.nhlbi.nih.gov/health/educational/hearttruth/lower-risk/risk-factors.htm

(12) Heart Disease Risk Calculator – Mayo Clinic Health System,

http://mayoclinichealthsystem.org/HeartRiskAssessment/index.html

(13) Coronary Artery Disease Risk Factors.htm,

http://en.wikipedia.org/wiki/Coronary_artery_disease

(14) Google Search: GWAS: Risk factors for Heart Attacks,

https://www.google.com/search?newwindow=1&site=&source=hp&q=GWAS+and+Risk+Factors+for+heart+attacks++Google+Scholar&oq=GWAS+and+Risk+Factors+for+heart+attacks+-+Google+Scholar&gs_l=hp.3..33i21.14398.14398.0.15615.1.1.0.0.0.0.68.68.1.1.0.msedr…0…1c.1.62.hp..0.1.68.BnhMLbcuN8w

(15) Cardiac Marker – Wikipedia, the free encyclopedia.htm, http://en.wikipedia.org/wiki/Cardiac_marker

(16) Coronary Artery Risk Factors – Google Search, https://www.google.com/search?newwindow=1&q=Coronary+Artery+Disease+Risk+Factors&oq=Coronary+Artery+Disease+Risk+Factors&gs_l=serp.3..0l6j0i22i30l4.644900.644900.0.646083.1.1.0.0.0.0.230.230.21.1.0.ehm_gd…0…1.1.62.serp..0.1.229.Rtr08Z0fHX4

(17) World Heart Federation, Cardiovascular Disease Risk Factors,

http://www.world-heart-federation.org/cardiovascular-health/cardiovascular-disease-risk-factors/

(18) Cardiovascular Disease – Risk Factors, National Health Services, UK, http://www.nhs.uk/conditions/cardiovascular-disease/pages/risk-factors.aspx

(19) Risk Factors for Heart Disease, WebMD, http://www.webmd.com/heart-disease/risk-factors-heart-disease

(20) Myocardial Infarction, http://en.wikipedia.org/wiki/Myocardial_infarction

(21) What is coronary angiography, (NHLB-NIH)?

http://www.nhlbi.nih.gov/health/health-topics/topics/ca/

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