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Vasoplegia in Orthotopic Heart Transplant Patients

Posted in Ecosystems & Industrial Concentration in the Medical Device Sector, FDA Regulatory Affairs, International Global Work in Pharmaceutical, Medical Devices R&D and Inventions, Nitric Oxide in Health and Disease, Pharmaceutical Industry Competitive Intelligence, Pharmaceutical R&D Investment, Pharmacotherapy of Cardiovascular Disease, Regulated Clinical Trials: Design, Methods, Components and IRB related issues, Systemic Inflammatory Response Related Disorders, Technology Transfer: Biotech and Pharmaceutical, tagged BMI, cardiothoracic surgery, Cheyne-Stokes Respiration, Conditions and Diseases, Heart Failure, Heart Lung Transplant, Larry H. Bernstein, mechanical support, surgery, thyroid disease, vasoplegia on June 30, 2013| Leave a Comment »

Pre-operative Risk Factors and Clinical Outcomes Associated with Vasoplegia in Recipients of Orthotopic Heart Transplantation in the Contemporary Era.

Writer and Curator: Larry H. Bernstein, MD, FCAP

and

Curator: Aviva Lev-Ari, PhD, RN 

 

 Patarroyo M, Simbaqueba C, Shrestha K, Starling RC, Smedira N, Tang WH, Taylor DO.

J Heart Lung Transplant. 2012 Mar;31(3):282-7.  http://dx.doi.org/10.1016/j.healun.2011.10.010  Epub 2011 Nov

 

BACKGROUND:  Patients who underwent orthotopic heart transplant (OHT) can develop vasoplegia, which is

• associated with high mortality and morbidity.

Herein we examine the per-operative risk in OHT recipients at Cleveland Clinic.  Vasoplegic syndrome is

• low systemic vascular resistance ( SVR index <1,600 dyn∙seg/cm5/m2 ) and
• high cardiac output ( cardiac index >2.5 l/min/m2 )
• within the first 4 postoperative hours.

VPS occurs more frequently after on pump CABG surgery versus off pump CABG surgery.

Methylene blue and vasoplegia: who, when, and how?

Stawicki SP, Sims C, Sarani B, Grossman MD, Gracias VH.

Department of Surgery, Division of Surgical Critical Care, University of Pennsylvania School of Medicine

Mini Rev Med Chem. 2008 May;8(5):472-90.  http://www.ncbi.nlm.nih.gov/pubmed/18473936

Vasoplegia or vasoplegic syndrome (VS) is thought to be due to

• dysregulation of endothelial homeostasis and subsequent endothelial dysfunction
• secondary to direct and indirect effects of multiple inflammatory mediators.

Vasoplegia has been observed in all age groups and in various clinical settings, such as anaphylaxis (including protamine reaction), sepsis, hemorrhagic shock, hemodialysis, and cardiac surgery. Among mechanisms thought to be contributory to VS, the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway appears to play a prominent role.

Methylene blue (MB),

• an inhibitor of nitric oxide synthase (NOS) and guanylate cyclase (GC),

has been found to improve

• the refractory hypotension associated with endothelial dysfunction of VS.

METHODS:  We reviewed peri-operative data from 311 consecutive adult patients who underwent OHT between January 2003 and June 2008.

Vasoplegia was defined as

1. persistent low systemic vascular resistance,
2. despite multiple intravenous pressor drugs at high dose,
3. between 6 and 48 hours after surgery.

RESULTS:  In our cohort of 311 patients, 35 (11%) patients developed vasoplegia syndrome; these patients were more likely to be UNOS Status 1A, with

• a higher body surface area (1.8 ± 0.25 vs 1.63 ± 0.36, p = 0.0007),
• greater history of thyroid disease (38.2% vs 18.5%, p = 0.0075) and
• a higher rate of previous cardiothoracic surgery (79% vs 48%, p = 0.0006).

Pre-operatively,

• they were more frequently treated with aspirin (73% vs 48%, p = 0.005) and
• mechanical assist devices (ventricular assist devices [VADs]: 45% vs 17%, p < 0.0001;
• total artificial hearts: 8.6% vs 0%, p < 0.0001), and
• less treated with milrinone (14.7% vs 45.8%, p = 0.0005).

Bypass time (118 ± 37 vs 142 ± 39 minutes, p = 0.0002) and

donor heart ischemic time (191 ± 46 vs 219 ± 51 minutes, p = 0.002) were longer, with

• higher mortality (3.2% vs 17.1%, p = 0.0003) and morbidity in the first 30 days after transplant.

In the multivariate analysis, history of thyroid disease (odds ratio [OR] = 2.7, 95% CI 1.0 to 7.0, p = 0.04) and VAD prior to transplant (OR = 2.8, 95% CI 1.07 to 7.4, p = 0.03)

• were independent risk factors for development of vasoplegia syndrome.

CONCLUSIONS:

1. High body mass index,
2. long cardiopulmonary bypass time,
3. prior cardiothoracic surgery,
4. mechanical support,
5. use of aspirin, and
6. thyroid disease

are risk factors associated with development of vasoplegia syndrome.

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• Decreased postoperative atrial fibrillation following cardiac transplantation (pharmaceuticalintelligence.com)
• 6-Year-Old Catonsville Girl Fights For Her Life After Heart Transplant (baltimore.cbslocal.com)
• One Year Later, Heart Transplant Recipient Doing Well (foxct.com)
• Girl on ventilator after lung transplants (cnn.com)

• Heart Failure Treatment Improves, But Death Rate Remains High : NPR (pharmaceuticalintelligence.com)
• Heart transplantation research in the next decade – a goal to achieving evidence-based outcomes (pharmaceuticalintelligence.com)
• Beta-Blocker Response (23andme.com)
• First drug to improve heart failure mortality in over a decade – HealthCanal.com (pharmaceuticalintelligence.com)
• Advanced heart failure (pharmaceuticalintelligence.com)
• Scientists prevent heart failure in mice (pharmaceuticalintelligence.com)

Other related articles fpublished on thie Open Access Online Sceintific Journal include the following:

Phrenic Nerve Stimulation in Patients with Cheyne-Stokes Respiration and Congestive Heart Failure (larryhbern)

http://pharmaceuticalintelligence.com/2013/06/20/phrenic-nerve-stimulation-in-patients-with-cheyne-stokes-respiration-and-congestive-heart-failure/
First drug to improve heart failure mortality in over a decade – HealthCanal.com (Aviva Lev-Ari)
http://pharmaceuticalintelligence.com/2013/06/03/first-drug-to-improve-heart-failure-mortality-in-over-a-decade-healthcanal-com/
Meta-analysis: Heart Failure Worsens Short-term Prognosis of NSTE-ACS Patients – TCTMD
(Aviva Lev-Ari)
http://pharmaceuticalintelligence.com/2013/06/06/meta-analysis-heart-failure-worsens-short-term-prognosis-of-nste-acs-patients-tctmd/

Scientists prevent heart failure in mice (Aviva Lev-Ari)
http://pharmaceuticalintelligence.com/2013/05/29/scientists-prevent-heart-failure-in-mice/
Economic Toll of Heart Failure in the US: Forecasting the Impact of Heart Failure in the United States – A Policy Statement From the American Heart Association (Aviva Lev-Ari)
http://pharmaceuticalintelligence.com/2013/04/25/economic-toll-of-heart-failure-in-the-us-forecasting-the-impact-of-heart-failure-in-the-united-states-a-policy-statement-from-the-american-heart-association/
Stenosis, ischemia and heart failure (Aviva Lev-Ari)
http://pharmaceuticalintelligence.com/2013/05/16/stenosis-ischemia-and-heart-failure/
Congestive Heart Failure & Personalized Medicine: Two-gene Test predicts response to Beta Blocker Bucindolol (Aviva Lev-Ari)
http://pharmaceuticalintelligence.com/2012/10/17/chronic-heart-failure-personalized-medicine-two-gene-test-predicts-response-to-beta-blocker-bucindolol/

Gene Therapy Into Healthy Heart Muscle: Reprogramming Scar Tissue In Damaged Hearts
(Aviva Lev-Ari)

http://pharmaceuticalintelligence.com/2013/01/09/gene-therapy-into-healthy-heart-muscle-reprogramming-scar-tissue-in-damaged-hearts/

Heart Renewal by pre-existing Cardiomyocytes: Source of New Heart Cell Growth Discovered
Aviva Lev-Ari)
http://pharmaceuticalintelligence.com/2012/12/23/heart-renewal-by-pre-existing-cardiomyocytes-source-of-new-heart-cell-growth-discovered/

Heart Remodeling by Design – Implantable Synchronized Cardiac Assist Device: Abiomed’s Symphony (Aviva lev-Ari)

http://pharmaceuticalintelligence.com/2012/07/23/heart-remodeling-by-design-implantable-synchronized-cardiac-assist-device-abiomeds-symphony/

Survivals Comparison of Coronary Artery Bypass Graft (CABG) and Percutaneous Coronary Intervention (PCI) / Coronary Angioplasty (larryhbern)
http://pharmaceuticalintelligence.com/2013/06/23/comparison-of-cardiothoracic-bypass-and-percutaneous-interventional-catheterization-survivals/
First case in the US: Valve-in-Valve (Aortic and Mitral) Replacements with Transapical Transcatheter Implants – The Use of Transfemoral Devices (larryhbern)
http://pharmaceuticalintelligence.com/2013/06/23/valve-in-valve-replacements-with-transapical-transcatheter-implants/
Ventricular Assist Device (VAD): A Recommended Approach to the Treatment of Intractable Cardiogenic Shock (larryhbern)
http://pharmaceuticalintelligence.com/2013/06/18/a-recommended-approach-to-the-treatmnt-of-intractable-cardiogenic-shock/
Trans-apical Transcatheter Aortic Valve Replacement in a Patient with Severe and Complex Left Main Coronary Artery Disease (LMCAD) (larryhbern)
http://pharmaceuticalintelligence.com/2013/06/17/management-of-difficult-trans-apical-transcatheter-aortic-valve-replacement-in-a-patient-with-severe-and-complex-arterial-disease/
Clinical Indications for Use of Inhaled Nitric Oxide (iNO) in the Adult Patient Market: Clinical Outcomes after Use, Therapy Demand and Cost of Care (Aviva Lev-Ari)
http://pharmaceuticalintelligence.com/2013/06/03/clinical-indications-for-use-of-inhaled-nitric-oxide-ino-in-the-adult-patient-market-clinical-outcomes-after-use-therapy-demand-and-cost-of-care/

Space-filling model of the cyclic guanosine monophosphate molecule, also known as cGMP, a nucleotide. This image shows the anionic (negatively charged) form. Colour code (click to show) : Black: Carbon, C : White: Hydrogen, H : Red: Oxygen, O : Blue: Nitrogen, N : Orange: Phosphorus, P (Photo credit: Wikipedia)

Ball-and-stick model of the cyclic guanosine monophosphate molecule, also known as cGMP, a nucleotide. This image shows the anionic (negatively charged) form. Colour code (click to show) : Black: Carbon, C : White: Hydrogen, H : Red: Oxygen, O : Blue: Nitrogen, N : Orange: Phosphorus, P (Photo credit: Wikipedia)

English: Drawing showing targets of cGMP in cells (Photo credit: Wikipedia)

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How Might Sleep Apnea Lead to Serious Health Concerns like Cardiac and Cancers?

Posted in Cancer Prevention: Research & Programs, Cell Biology, Signaling & Cell Circuits, Chemical Biology and its relations to Metabolic Disease, Health Economics and Outcomes Research, Medical and Population Genetics, Nutrition, Origins of Cardiovascular Disease, Population Health Management, Nutrition and Phytochemistry, Systemic Inflammatory Response Related Disorders, tagged ApneaSleep, BMI, Body mass index, Cancer - General, CPAP, Diabetes mellitus type 2, metabolic syndrome, Obstructive sleep apnea, OSA, Pasteur effect, physical activity, Positive airway pressure, Sleep apnea, Sleep disorder, subjective global assessment, type 2 DM on March 20, 2013| 2 Comments »

How Might Sleep Apnea Lead to Serious Health Concerns like Cardiac and Cancer?

Author: Larry H Bernstein, MD, FCAP

3.3.16   How Might Sleep Apnea Lead to Serious Health Concerns like Cardiac and Cancer?, Volume 2 (Volume Two: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS and BioInformatics, Simulations and the Genome Ontology), Part 2: CRISPR for Gene Editing and DNA Repair

UPDATED on 7/23/2019

Israel-led research team develops AI-based model to detect sleep apnea | The Times of Israel

https://www.timesofisrael.com/israel-led-research-team-develops-ai-based-model-to-detect-sleep-apnea/?utm_source=dlvr.it

What is the link between sleep apnea and cardiovascular disease and is the treatment of obstructive sleep apnea (OSA) by continuous positive airway pressure in patients (CPAP) with heart failure to improve left ventricular systolic function sufficient?  There are statistics incicating the benefit of CPAP and improvement of LVSF in those patients on CPAP with CHF.  But that observation does not get at why the patients benefit, or whether the OSA is sufficient.  Don’t expect a randomized clinical trial of any design to be brought to bear on the subject, considering the ethical issues involved.  We’ll return to that in a moment.

In a recent study researchers in Spain followed thousands of patients at sleep clinics and found that those with the most severe forms of sleep apnea had a 65 percent greater risk of developing cancer of any kind. The second study, of about 1,500 government workers in Wisconsin, showed that those with the most disordered sleep had five times the rate of dying from cancer as people without the sleep disorder (apnea not specified). Both research teams only looked at cancer diagnoses and outcomes in general.  If I lump the two studies, assuming that all patients with the most disordered sleep had OSA and were on CPAP, what does this tell us?  The heart and lung function together as a cardiopulmonary oxygenation unit!  A problem disrupting oxygenation, such as autonomically controlled sleep disruption or, oronasal obstruction (ASSOCIATED WITH SNORING), would be expected to have an effect on alertness during the day, predisposition to CHF from strain on the CP circulation as well as ventilatory impairment and peripheral oxygenation.  It appears that an association with ANY cancer, unspecified, is a long reach.

In both studies the researchers ruled out the possibility that the usual risk factors for cancer, like

1. age
2. smoking
3. alcohol use
4. physical activity
5. weight

The association between cancer and disordered breathing at night remained

• even after they adjusted for confounding variables.

This led to the conclusion that cancer might be linked to (intermittent) lack of oxygen supply interrupting aerobic cell activity over long periods of time.  The conclusion is drawn that from two associations

• the research on positive outcome from CPAP in OSA and
• a possible link between breathing and cardiac and cancer clearly

demonstrates the importance of regular breathing exercises (other wise known as ‘Pranayama’ in India) as part of our every day life.

This answers the first observation I posed. That is, the use of CPAP, while enormously important, is not sufficient.  Regular breathing exercises would seem to be helpful, although not a standard part of current treatment. This would be especially important if the movement of the abdominal muscles and diaphragm were synchronized with the expansion of the nthorax for maximum air flow.  This observation is familiar from working with a certified exercise physiologist.   The other part of this is an optimum time for walking and carrying out basic muscle and flexibility exercises several times a week, which has been shown repeatedly by studies on health benefits.

It is not my place to raise some questions about the way the studies were carried out.  The patients who have sleep apnea would be expected to have an increased body mass index (BMI), and while not sarcopenic, more likely to have excess body fat, abdominal distribution in males, and hip distribution in females, amd more importantly, unseen fat in the abdominal peritoneum.  This is related to type 2 diabetes with a metabolic syndrome, a separate indicator of CVD risk.   The metabolic syndrome involves TNF-alpha (once also known as cachexin), IL-1, IL-6, C-reactive protein, and in the case of fat signaling, adipokines, as well as insulin resistance and, as a result, some counter-regulatory secretion of glucocorticosteroids.  This metabolic picture would result in the following:

1. impaired glucose utilization
2. some excess and uncompensated gluconeogenesis
3. the impaired lactate reentry at the end of glycolysis
4. an effect on allosteric PFK

Features 1-4 look like what Warburg called a Pasteur Effect, not at the clellular level, but in the whole individual.   While obesity and type 2 diabetes are occuring in the young and adolescent population, the consequences might not be seen until years later.  The consequences could be in a middle aged person falling asleep at a meeting, or a series of automabile accidents related to falling asleep at the wheel.

At a time that clinical laboratory measurements are so accurate, and

• the associations between type 2 diabetes,
• measurement of wt/ht^2,
• arm strength,
• skin fold thickness,

are common measures of fitness, they don’t appear to have any place in these studies. If that is the case, then how is it possible to make sense of a relationship between SEVERITY of sleep disturbance and health outcome.

http://www.nejm.org/doi/full/10.1056/NEJMoa022479#t=articleTop

http://well.blogs.nytimes.com/2012/05/20/sleep-apnea-tied-to-increased-cancer-risk/

http://www.medicalnewstoday.com/articles/245649.php

http://www.sciencenews.org/view/generic/id/340838/title/Severe_s

Related articles

• Sleep Apnea (topdentists.com)
• What Are Sleep Apnea Causes? (topdentists.com)
• Sleep disorder increases risk of brain cancer: Taiwan doctor (wantchinatimes.com)
• Think Sleep Apnea is Just Snoring and Sleepiness? Think Again (sleephelpdesk.wordpress.com)

English: The Cycle of Obstructive Sleep Apnea – OSA (Photo credit: Wikipedia)

English: The graph shows the correlation between body mass index (BMI) and percent body fat (%BF) for men in NCHS’ NHANES III 1994 data. The body fat percent shown uses the method from Romero-Corral et al. to convert NHANES BIA to %BF (June 2008). “Accuracy of body mass index in diagnosing obesity in the adult general population”. International Journal of Obesity 32 (6) : 959–956. DOI:10.1038/ijo.2008.11. PMID 18283284. (Photo credit: Wikipedia)

English: Body mass index, BMI, body size, body weight, mortality Italiano: indice di massa corporea, IMC, altezza corporea, peso corporeo, mortalità (Photo credit: Wikipedia)

Italiano: biometria, epidemiologia, rischio, peso corporeo umano, mortalità, indice di massa corporea, IMC, body mass index, BMI, prospective studies collaboration (Photo credit: Wikipedia)

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Extended sleep at night is protective by suppressing expression of obesity genes.

Posted in Chemical Biology and its relations to Metabolic Disease, Population Health Management, Genetics & Pharmaceutical, tagged BMI, Body mass index, Body weight, Carbohydrate metabolism, genetics, health, Obesity, science, sleep, Sleep disorder, University of Washington, weight, Weight gain on May 10, 2012| 2 Comments »

Main health effects of sleep deprivation (See Wikipedia:Sleep deprivation). Model: Mikael Häggström. To discuss image, please see Template talk:Häggström diagrams (Photo credit: Wikipedia)

Reporter: Venkat Karra, Ph.D.

Sleep may influence weight by affecting hormones, glucose metabolism and inflammation, say scientists. A new study has found that sleeping more than nine hours a night appears to suppress genetic factors that lead to weight gain. In contrast, getting too little sleep seems to have the opposite effect. Adding a few hours sleep to your night may prevent you from gaining weight. These new findings reveal a complex interaction between sleep and genetic factors linked to body weight.

The study found heritability of body mass index (BMI) — a measurement relating weight and height — was twice as high for short than for long sleepers.

Thus sleep well and stay healthy.

source

 Article:

Sleep Duration and Body Mass Index in Twins: A Gene-Environment Interaction

by Nathaniel F. Watson, MD, MSc; Kathryn Paige Harden, PhD; Dedra Buchwald, MD; Michael V. Vitiello, PhD; Allan I. Pack, MB ChB, PhD; David S. Weigle, MD; Jack Goldberg, PhD

Sleep, Volume 35/ Issue 05 / Tuesday, May 01, 2012

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