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Cardiovascular Original Research: Cases in Methodology Design for Content Curation and Co-Curation

Author: Aviva Lev-Ari, PhD, RN

For a general article on Science and Curation, go to

Science and Curation: the New Practice of Web 2.0

Since 4/2012, Leaders in Pharmaceutical Business Intelligence, is developing an innovative methodology for the facilitation of Global access to Biomedical knowledge rather than the access to sheer search results on Scientific subject matters in the Life Sciences and Medicine. For the methodology to attain this complex goal it is to be dealing with popularization of ORIGINAL Scientific Research via Content Curation of Scientific Research Results by Experts, Authors, Writers using the critical  thinking process of expert interpretation of the original research results. We demonstrate in this article two approaches to the process of reaching that goal successfully.

Editorial Team Members and Five Series of e-Bookd in BioMed

Series A: e-Books on Cardiovascular Diseases

Content Consultant: Justin D Pearlman, MD, PhD, FACC

Volume One: Perspectives on Nitric Oxide

Sr. Editor: Larry Bernstein

Editor: Aviral Vatsa

Content Consultant: Stephen J Williams

available on Kindle Store @ Amazon.com

http://www.amazon.com/dp/B00DINFFYC

Volume Two: Cardiovascular Original Research: Cases in Methodology Design for Content Co-Curation

Curators: Justin D Pearlman, Larry H Bernstein, Aviva Lev-Ari

  • Causes
  • Risks and Biomarkers
  • Therapeutic Implications

Volume Three: Etiologies of CVD: Epigenetics, Genetics & Genomics

Curators: Larry H Bernstein and Aviva Lev-Ari

  • Causes
  • Risks and Biomarkers
  • Therapeutic Implications

Chapter 1: Genomics and Medicine by Marcus Feldman

Volume Four: Therapeutic Promise: CVD, Regenerative & Translational Medicine

Curators: Larry H Bernstein and Aviva Lev-Ari

  • Causes
  • Risks and Biomarkers
  • Therapeutic Implications

Volume Five: Pharmaco-Therapies for CVD

Curators: Vivek Lal, Larry H Bernstein and Aviva Lev-Ari

  • Causes
  • Risks and Biomarkers
  • Therapeutic Implications

Volume Six: Interventional Cardiology and Cardiac Surgery

Curators: Justin D Pearlman, Larry H Bernstein, Aviva Lev-Ari

  • Causes
  • Risks and Biomarkers
  • Therapeutic Implications

Volume Seven: CVD Imaging for Disease Diagnosis and Guidance of Treatment

Curators: Justin D Pearlman and Aviva Lev-Ari

  • Causes
  • Risks and Biomarkers
  • Therapeutic Implications

Series B: e-Books on Genomics & Medicine

Content Consultant: Larry H Bernstein, MD, FCAP

Volume 1: Genomics and Individualized Medicine

Sr. Editor: Stephen J Williams

Editors: Larry H Bernstein and Aviva Lev-Ari

Volume 2: Methodological Breakthroughs in NGS

Editor: Marcus Feldman

Volume 3: Institutional Leadership in Genomics

Editors: Marcus Feldman and Aviva Lev-Ari 

Series C: e-Books on Cancer & Oncology

Content Consultant: Larry H Bernstein, MD, FCAP

Volume 1: Cancer and Genomics

Sr. Editor: Stephen J Williams

Editors: Ritu Saxena, Tilda Barliya

Volume 2: Immunotherapy in Oncology

Sr. Editor: Stephen J Williams

Editors: Tilda Barliya and Demet Sag

Volume 3: Nanotechnology and Drug Delivery

Editor and Author: Tilda Barliya

Series D: e-Books on BioMedicine

Volume 1: Metabolomics

Sr. Editors: Larry H Bernstein and

Editor: Ritu Saxena 

Volume 2: Infectious Diseases

Editor: TBA

Volume 3: Immunology and Therapeutics

Editor: TBA

Series E: Titles in the Strategic Plan for 2014 – 2015

Volume 1: The Patient’s Voice: Personal Experience with Invasive Medical Procedures

Editor: TBA 

Volume 2: Interviews with Scientific Leaders

Editor: TBA

Volume 3: Infectious Milestones in Physiology – Discoveries in Medicine

Editor: TBA

[affiliate] Dr. Pnina G. Abir-Am, Belmont, MA – Independent AUTHOR, History of Molecular Biology

Dr. Aviva Lev-Ari, Boston, MA – Editor-in-Chief, BioMed Series, Editor – Genomics Volume One

Site Statistics

Date

Views to Date

# of articles

NIH Clicks

Nature Clicks

6/24/2013

199,857

1,034

1,275

661

7/29/2013  217,356  1,138  1,389  705
9/11/2013   238,937  1,202  1,495  735
9/26/2013  249,535  1,221  1,570  759

Date

Views to Date

# of articles

NIH Clicks

Nature Clicks

10/14/2013

260,043

1,252

1,593

781

 

This article has two parts:

Part I: The Curator as a Scientific Content Critique for the Architecture of Knowledge, its meaning and its societal implications.

Part II: Cases in Co-Curation and Scientific Content Critique

In Part I, one curator edifies the e-Reader via his/hers OWN creative mental processes of knowledge synthesis following the creative mental process of analytical critique. The outcome is a new FORM of writing Science and of writing about Science, as well as, a new FORM of framework been created for the organization of the interrelations exposed in the analytical phase of a dialectically generated original synthesis, the process of which is manifold: the structure of the knowledge presented, culling in the midst of inclusion/exclusion dialectics and finally the Curator’s own original synthetic statements of the new Art, a new conceptual perspective on Science.

  • For our VISION, See

https://pharmaceuticalintelligence.com/vision/

  • For periodic updates to the List of Cases developed by this Author/Curator, see

https://pharmaceuticalintelligence.com/contributors-biographies/aviva-lev-ari/

  • For a complete contribution to the Open Access Online Scientific Journal by the Author/Curator, see

http://pharmaceuticalintelligence.com — Search by Author/Curator’s Last Name, 567 articles on 7/30/2013

  • For the BioMed e-Books Series in Production, see

https://pharmaceuticalintelligence.com/biomed-e-books/

  • FIRST book of their BioMedical E-Book Series, Perspectives on Nitric Oxide in Disease Mechanisms, now available on Amazon.com Kindle Store

http://www.amazon.com/dp/B00DINFFYC

  • For CV of our entire Team of Experts, Authors, Writers, see

https://pharmaceuticalintelligence.com/contributors-biographies/

In part Part II: Cases in Co-Curation and Scientific Content Critique, are presented. A similar process to the one in Part I, is been applied. However, the Co-Curation, brings on stage several players. The Actors in the Scientific Writers Theater,  all own scientific knowledge and master the process of creation of a new Synthesis for most writing engagements. Since the Co-curators are educated in different disciplines, they are skillfully providing interpretations for others’ and their own new conception of ideas. Thus, they are developing new views of the original scientific results presented in peer reviewed journals, just the leading ones in every field. The Co-Curators, their creation is a new layer of comprehension for the processes at hand.

Example #1:

Action Potential, a well define concept in Physiology. For us,  Action Potential was a conceptual creation for the process of Co-Curation. Dr. Lev-Ari, requesting Dr. Bernstein to elaborate creatively, on the function of actin in cytoskeleton mobility, he did,  THEN a new conceptual creation process emerged and had YIELDED the following article:

Identification of Biomarkers that are Related to the Actin Cytoskeleton

Curator: Larry H Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2012/12/10/identification-of-biomarkers-that-are-related-to-the-actin-cytoskeleton/

Example #2:

The e-Reader reads first

High Serum Calcium Linked to Developing Diabetes: IRAS Study

 Sep 24, 2013

http://www.medscape.com/viewarticle/811536

The e-Reader reads second the curation of that Source Interview

Diabetes-risk Forecasts: Serum Calcium in Upper-Normal Range (>2.5 mmol/L) as a New Biomarker

https://pharmaceuticalintelligence.com/2013/09/25/diabetes-risk-forecasts-serum-calcium-in-upper-normal-range-2-5-mmoll-as-a-new-biomarker/

The e-Reader will compare which of the two is more beneficial for the e-Reader.

We believe that the curation of the Source Interview has remarkable value added analysis that the Reader can benefit from.

The unique process as described for Part I and for Part II, above, will be demonstrated, below,  in concrete cases, as we applied the methodology of curation by one or by several Experts, Authors, Writers in the field of Cardiovascular Diseases.

The Process: We culled the scene for Cardiovascular Original Research in +24 Journals, we pre-select domains of research to cover: The Etiology of the Disease, the Risks of dysfunction at cellular, tissue, organelle, organ, anatomy, physiology, pathophysiology and diagnostics for all of the above. We interpret the Disease Management Options in a comprehensive fashion, exposing the e-Reader to an integrative approach for the treatment of Cardiovascular Disease.

Below,  the e-Reader finds selective cases exemplifying the methodology described, making

the one and only on the Internet and in e-Book Stores, to date.

 

Part I       

The Curator as a Scientific Content Critique for the Architecture of Knowledge

Lev-Ari, A. 8/6/2013 Stent Design and Thrombosis:  Bifurcation Intervention, Drug Eluting Stents (DES) and Biodegrable Stents

https://pharmaceuticalintelligence.com/2013/08/06/stent-design-and-thrombosis-bifurcation-intervention-drug-eluting-stents-des-and-biodegrable-stents/

Lev-Ari, A. 8/1/2013 Calcium Cycling (ATPase Pump) in Cardiac Gene Therapy: Inhalable Gene Therapy for Pulmonary Arterial Hypertension and Percutaneous Intra-coronary Artery Infusion for Heart Failure: Contributions by Roger J. Hajjar, MD

https://pharmaceuticalintelligence.com/2013/08/01/calcium-molecule-in-cardiac-gene-therapy-inhalable-gene-therapy-for-pulmonary-arterial-hypertension-and-percutaneous-intra-coronary-artery-infusion-for-heart-failure-contributions-by-roger-j-hajjar/

Lev-Ari, A. 7/19/2013 3D Cardiovascular Theater – Hybrid Cath Lab/OR Suite, Hybrid Surgery, Complications Post PCI and Repeat Sternotomy

https://pharmaceuticalintelligence.com/2013/07/19/3d-cardiovascular-theater-hybrid-cath-labor-suite-hybrid-surgery-complications-post-pci-and-repeat-sternotomy/

Lev-Ari, A. 7/14/2013 Vascular Surgery: International, Multispecialty Position Statement on Carotid Stenting, 2013 and Contributions of a Vascular Surgeon at Peak Career – Richard Paul Cambria, MD

https://pharmaceuticalintelligence.com/2013/07/14/vascular-surgery-position-statement-in-2013-and-contributions-of-a-vascular-surgeon-at-peak-career-richard-paul-cambria-md-chief-division-of-vascular-and-endovascular-surgery-co-director-thoracic/

Lev-Ari, A. 7/9/2013 Heart Transplant (HT) Indication for Heart Failure (HF): Procedure Outcomes and Research on HF, HT @ Two Nation’s Leading HF & HT Centers

https://pharmaceuticalintelligence.com/2013/07/09/research-programs-george-m-linda-h-kaufman-center-for-heart-failure-cleveland-clinic/

Lev-Ari, A. 7/8/2013 Becoming a Cardiothoracic Surgeon: An Emerging Profile in the Surgery Theater and through Scientific Publications

https://pharmaceuticalintelligence.com/2013/07/08/becoming-a-cardiothoracic-surgeon-an-emerging-profile-in-the-surgery-theater-and-through-scientific-publications/

Lev-Ari, A. 7/1/22013 Endovascular Lower-extremity Revascularization Effectiveness: Vascular Surgeons (VSs), Interventional Cardiologists (ICs) and Interventional Radiologists (IRs)

https://pharmaceuticalintelligence.com/2013/07/01/endovascular-lower-extremity-revascularization-effectiveness-vascular-surgeons-vss-interventional-cardiologists-ics-and-interventional-radiologists-irs/

Lev-Ari, A. 6/10/2013 No Early Symptoms – An Aortic Aneurysm Before It Ruptures – Is There A Way To Know If I Have it?

https://pharmaceuticalintelligence.com/2013/06/10/no-early-symptoms-an-aortic-aneurysm-before-it-ruptures-is-there-a-way-to-know-if-i-have-it/

Lev-Ari, A. 6/9/2013 Congenital Heart Disease (CHD) at Birth and into Adulthood: The Role of Spontaneous Mutations

https://pharmaceuticalintelligence.com/2013/06/09/congenital-heart-disease-at-birth-and-into-adulthood-the-role-of-spontaneous-mutations-the-genes-and-the-pathways/

Lev-Ari, A. 6/3/2013 Clinical Indications for Use of Inhaled Nitric Oxide (iNO) in the Adult Patient Market: Clinical Outcomes after Use, Therapy Demand and Cost of Care

https://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/

Lev-Ari, A. 6/2/2013 Inhaled Nitric Oxide in Adults: Clinical Trials and Meta Analysis Studies – Recent Findings

https://pharmaceuticalintelligence.com/2013/06/02/inhaled-nitric-oxide-in-adults-with-acute-respiratory-distress-syndrome/

Lev-Ari, A. 5/17/2013 Synthetic Biology: On Advanced Genome Interpretation for Gene Variants and Pathways: What is the Genetic Base of Atherosclerosis and Loss of Arterial Elasticity with Aging

https://pharmaceuticalintelligence.com/2013/05/17/synthetic-biology-on-advanced-genome-interpretation-for-gene-variants-and-pathways-what-is-the-genetic-base-of-atherosclerosis-and-loss-of-arterial-elasticity-with-aging/

Lev-Ari, A. 4/28/2013 Genetics of Conduction Disease: Atrioventricular (AV) Conduction Disease (block): Gene Mutations – Transcription, Excitability, and Energy Homeostasis

https://pharmaceuticalintelligence.com/2013/04/28/genetics-of-conduction-disease-atrioventricular-av-conduction-disease-block-gene-mutations-transcription-excitability-and-energy-homeostasis/

Lev-Ari, A. 2/28/2013 The Heart: Vasculature Protection – A Concept-based Pharmacological Therapy including THYMOSIN

https://pharmaceuticalintelligence.com/2013/02/28/the-heart-vasculature-protection-a-concept-based-pharmacological-therapy-including-thymosin/

Part II         

Cases in Co-Curation and Scientific Content Critique

Pearlman, JD, and A.  Lev-Ari, 9/30/2013

State of Cardiology on Wall Stress, Ventricular Workload and Myocardial Contractile Reserve: Aspects of Translational Medicine(TM)

https://pharmaceuticalintelligence.com/2013/09/30/state-of-cardiology-on-wall-stress-ventricular-workload-and-myocardial-contractile-reserve-aspects-of-translational-medicine/

Lal, V, Pearlman JD, and A. Lev-Ari, 9/23/2013

Do Novel Anticoagulants Affect the PT/INR? The Cases of  XARELTO (rivaroxaban) or PRADAXA (dabigatran)

https://pharmaceuticalintelligence.com/2013/09/23/do-novel-anticoagulants-affect-the-ptinr-the-cases-of-xarelto-rivaroxaban-and-pradaxa-dabigatran/

Bernstein LH, SJ Williams and A. Lev-Ari, 8/26/2013

Part II: Role of Calcium, the Actin Skeleton, and Lipid Structures in Signaling and Cell Motility

https://pharmaceuticalintelligence.com/2013/08/26/role-of-calcium-the-actin-skeleton-and-lipid-structures-in-signaling-and-cell-motility/

Bernstein LH, SJ Williams and A. Lev-Ari,  9/2/2013

Part III: Renal Distal Tubular Ca2+ Exchange Mechanism in Health and Disease

https://pharmaceuticalintelligence.com/2013/09/02/renal-distal-tubular-ca2-exchange-mechanism-in-health-and-disease/

Bernstein LH, Pearlman JD and A. Lev-Ari, 9/8/2013

Part IV: The Centrality of Ca(2+) Signaling and Cytoskeleton Involving Calmodulin Kinases and Ryanodine Receptors in Cardiac Failure, Arterial Smooth Muscle, Post-ischemic Arrhythmia, Similarities and Differences, and Pharmaceutical Targets

https://pharmaceuticalintelligence.com/2013/09/08/the-centrality-of-ca2-signaling-and-cytoskeleton-involving-calmodulin-kinases-and-ryanodine-receptors-in-cardiac-failure-arterial-smooth-muscle-post-ischemic-arrhythmia-similarities-and-differen/

Bernstein LH, Pearlman JD and A. Lev-Ari, 8/26/2013

Part V: Heart, Vascular Smooth Muscle, Excitation-Contraction Coupling (E-CC), Cytoskeleton, Cellular Dynamics and Ca2 Signaling

https://pharmaceuticalintelligence.com/2013/08/26/heart-smooth-muscle-excitation-contraction-coupling-cytoskeleton-cellular-dynamics-and-ca2-signaling/

Pearlman, JD, Bernstein, HL and A. Lev-Ari 8/28/2013

Part VII: Cardiac Contractility & Myocardium Performance: Ventricular Arrhythmias and Non-ischemic Heart Failure – Therapeutic Implications for Cardiomyocyte Ryanopathy (Calcium Release-related Contractile Dysfunction) and Catecholamine Responses

https://pharmaceuticalintelligence.com/2013/08/28/cardiac-contractility-myocardium-performance-ventricular-arrhythmias-and-non-ischemic-heart-failure-therapeutic-implications-for-cardiomyocyte-ryanopathy-calcium-release-related-contractile/

Pearlman, JD, Bernstein, LH and A. Lev-Ari, 9/12/2013

Part VIII: Disruption of Calcium Homeostasis: Cardiomyocytes and Vascular Smooth Muscle Cells: The Cardiac and Cardiovascular Calcium Signaling Mechanism

https://pharmaceuticalintelligence.com/2013/09/12/disruption-of-calcium-homeostasis-cardiomyocytes-and-vascular-smooth-muscle-cells-the-cardiac-and-cardiovascular-calcium-signaling-mechanism/

Pearlman, JD, Bernstein, LH and A. Lev-Ari, 9/16/2013

Part IX: Calcium-Channel Blockers, Calcium Release-related Contractile Dysfunction (Ryanopathy) and Calcium as Neurotransmitter Sensor

https://pharmaceuticalintelligence.com/2013/09/16/calcium-channel-blocker-calcium-as-neurotransmitter-sensor-and-calcium-release-related-contractile-dysfunction-ryanopathy/

Bernstein, LH and A. Lev-Ari, 9/10/2013

Part X: Synaptotagmin functions as a Calcium Sensor: How Calcium Ions Regulate the fusion of vesicles with cell membranes during Neurotransmission

https://pharmaceuticalintelligence.com/2013/09/10/synaptotagmin-functions-as-a-calcium-sensor-how-calcium-ions-regulate-the-fusion-of-vesicles-with-cell-membranes-during-neurotransmission/

Pearlman JD and A. Lev-Ari 8/25/2013

Coronary Circulation Combined Assessment: Optical Coherence Tomography (OCT), Near-Infrared Spectroscopy (NIRS) and Intravascular Ultrasound (IVUS) – Detection of Lipid-Rich Plaque and Prevention of Acute Coronary Syndrome (ACS)

https://pharmaceuticalintelligence.com/2013/08/25/coronary-circulation-combined-assessment-optical-coherence-tomography-oct-near-infrared-spectroscopy-nirs-and-intravascular-ultrasound-ivus-detection-of-lipid-rich-plaque-and-prevention-of-a/

Pearlman, JD, Bernstein, LH and A. Lev-Ari 8/5/2013

Alternative Designs for the Human Artificial Heart: The Patients in Heart Failure – Outcomes of Transplant (donor)/Implantation (artificial) and Monitoring Technologies for the Transplant/Implant Patient in the Community. To be submitted to Heart Failure Society of America (HFSA)

https://pharmaceuticalintelligence.com/2013/08/05/alternative-designs-for-the-human-artificial-heart-the-patients-in-heart-failure-outcomes-of-transplant-donorimplantation-artificial-and-monitoring-technologies-for-the-transplantimplant-pat/

Pearlman, JD and A. Lev-Ari 7/23/2013

Cardiovascular Complications: Death from Reoperative Sternotomy after prior CABG, MVR, AVR, or Radiation; Complications of PCI; Sepsis from Cardiovascular Interventions

https://pharmaceuticalintelligence.com/2013/07/23/cardiovascular-complications-of-multiple-etiologies-repeat-sternotomy-post-cabg-or-avr-post-pci-pad-endoscopy-andor-resultant-of-systemic-sepsis/

Pearlman, JD and A. Lev-Ari 7/22/2013

Cardiac Resynchronization Therapy (CRT) to Arrhythmias: Pacemaker/Implantable Cardioverter Defibrillator (ICD) Insertion

https://pharmaceuticalintelligence.com/2013/07/22/cardiac-resynchronization-therapy-crt-to-arrhythmias-pacemakerimplantable-cardioverter-defibrillator-icd-insertion

Pearlman, JD and A. Lev-Ari 7/17/2013

Emerging Clinical Applications for Cardiac CT: Plaque Characterization, SPECT Functionality, Angiogram’s and Non-Invasive FFR

https://pharmaceuticalintelligence.com/2013/07/17/emerging-clinical-applications-for-cardiac-ct-plaque-characterization-spect-functionality-angiograms-and-non-invasive-ffr/

Pearlman, JD and A. Lev-Ari 7/4/2013

Fractional Flow Reserve (FFR) & Instantaneous wave-free ratio (iFR): An Evaluation of Catheterization Lab Tools for Ischemic Assessment

https://pharmaceuticalintelligence.com/2013/07/04/fractional-flow-reserve-ffr-instantaneous-wave-free-rario-ifr-an-evaluation-of-catheterization-lab-tools-for-ischemic-assessment/

Pearlman, JD and A. Lev-Ari 5/24/2013

Imaging Biomarker for Arterial Stiffness: Pathways in Pharmacotherapy for Hypertension and Hypercholesterolemia Management

https://pharmaceuticalintelligence.com/2013/05/24/imaging-biomarker-for-arterial-stiffness-pathways-in-pharmacotherapy-for-hypertension-and-hypercholesterolemia-management/

Pearlman, JD and A. Lev-Ari 5/22/2013

Acute and Chronic Myocardial Infarction: Quantification of Myocardial Perfusion Viability – FDG-PET/MRI vs. MRI or PET alone

https://pharmaceuticalintelligence.com/2013/05/22/acute-and-chronic-myocardial-infarction-quantification-of-myocardial-viability-fdg-petmri-vs-mri-or-pet-alone/

Pearlman JD, LH Bernstein and A. Lev-Ari 5/15/2013

Diagnosis of Cardiovascular Disease, Treatment and Prevention: Current & Predicted Cost of Care and the Promise of Individualized Medicine Using Clinical Decision Support Systems

https://pharmaceuticalintelligence.com/2013/05/15/diagnosis-of-cardiovascular-disease-treatment-and-prevention-current-predicted-cost-of-care-and-the-promise-of-individualized-medicine-using-clinical-decision-support-systems-2/

Pearlman, JD and A. Lev-Ari 5/11/2013

Hypertension and Vascular Compliance: 2013 Thought Frontier – An Arterial Elasticity Focus

https://pharmaceuticalintelligence.com/2013/05/11/arterial-elasticity-in-quest-for-a-drug-stabilizer-isolated-systolic-hypertension-caused-by-arterial-stiffening-ineffectively-treated-by-vasodilatation-antihypertensives/

Pearlman, JD and A. Lev-Ari 5/7/2013

On Devices and On Algorithms: Arrhythmia after Cardiac Surgery Prediction and ECG Prediction of Paroxysmal Atrial Fibrillation Onset

https://pharmaceuticalintelligence.com/2013/05/07/on-devices-and-on-algorithms-arrhythmia-after-cardiac-surgery-prediction-and-ecg-prediction-of-paroxysmal-atrial-fibrillation-onset/

Pearlman, JD and A. Lev-Ari 5/4/2013

Clinical Decision Support Systems for Management Decision Making of Cardiovascular Diseases

https://pharmaceuticalintelligence.com/2013/05/04/cardiovascular-diseases-decision-support-systems-for-disease-management-decision-making/

Lev-Ari, A. and LH Bernstein 3/7/2013

Genomics & Genetics of Cardiovascular Disease Diagnoses: A Literature Survey of AHA’s Circulation Cardiovascular Genetics, 3/2010 – 3/2013

https://pharmaceuticalintelligence.com/2013/03/07/genomics-genetics-of-cardiovascular-disease-diagnoses-a-literature-survey-of-ahas-circulation-cardiovascular-genetics-32010-32013/

Find out more:

« Curation is the new research, »… et le nouveau média, Benoit Raphael, 2011http://benoitraphael.com/2011/01/17/curation-is-the-new-search/

La curation : la révolution du webjournalisme?, non-fiction.fr http://www.nonfiction.fr/article-4158-la_curation__la_revolution_du_webjournalisme_.htm

La curation : les 10 raisons de s’y intéresser, Pierre Tran http://pro.01net.com/editorial/529947/la-curation-les-10-raisons-de-sy-interesser/

Curation : quelle valeur pour les entreprises, les médias, et sa « marque personnelle »?, Marie-Laure Vie http://marilor.posterous.com/curation-et-marketing-de-linformation

Cracking Open the Scientific Process, Thomas Lin, New York Timeshttp://www.nytimes.com/2012/01/17/science/open-science-challenges-journal-tradition-with-web-collaboration.html?_r=4&pagewanted=1

La « massification » du web transforme les relations sociales, Valérie Varandat, INRIAhttp://www.inria.fr/actualite/actualites-inria/internet-du-futur

Internet a révolutionné le métier de chercheur, AgoraVoxhttp://www.agoravox.fr/actualites/technologies/article/internet-a-revolutionne-le-metier-103514

Gérer ses références numériques, Université de Genèvehttp://www.unige.ch/medecine/udrem/Unit/actualites/biblioManager.html

Notre liste Scoop-it : Scientific Social Network, MyScienceWork

SOURCE on Curation and Science

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Becoming a Cardiothoracic Surgeon: An Emerging Profile in the Surgery Theater and through Scientific Publications 

Author and Curator: Aviva Lev-Ari, PhD, RN

Two components of an Emerging Profile of a Young Cardiothoracic Surgeon were researched by the Author for the case of  Dr. Isaac George, Assistant Professor of Surgery, Division of Cardiothoracic Surgery, Department of Surgery, New York Presbyterian Hospital/Columbia University Medical Center , New York, NY.

The two components being:

1. the Cardiothoracic Surgery Theater

2. the Scientific Publications

I noted with interest Dr. George’s second publication, to be about a very well known surgeon in the US and Europe, John Benjamin Murphy. written by Dr. George and two other colleagues,  George I, Hardy MA, Widmann WD. published in Curr Surg. 2004 Sep-Oct;61(5):439-41.

Dr. Murphy, is best remembered for the eponymous clinical sign that is used in evaluating patients with acute cholecystitis. His career spanned general surgery, orthopedicsneurosurgery, and cardiothoracic surgery, which helped him to gain international prominence in the surgical profession. Mayo Clinic co-founder William James Mayo called him “the surgical genius of our generation.”

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

[Musana, Kenneth and Steven H. Yale (May 2005). “John Benjamin Murphy (1857–1916)”. Clinical Medicine & Research. Retrieved 2008-05-16.]

I assume that Dr. Murphy’s contributions to Thoracic surgery were of interest to Dr. George to inspire him to write on the subject and elect that Specialty in Surgery.

Murphy was first in the U.S. to induce (1898) artificial immobilization and collapse of the lung in treatment of pulmonary tuberculosis. He was a pioneer in the use of bone grafting and made contributions to the understanding and management of ankylosis as well as independently proposing artificial pneumothorax to manage unilateral lung disease in tuberculosis.

        «It is the purpose of every man’s life to do something worthy of the recognition and appreciation of his fellow men. . . . By their superior intellectual qualifications, their fidelity to purpose and above all their indefatigable labour the few become leaders.»

Journal of the American Medical Association, Chicago, 1911, 57: 1.

SOURCE Whonamedit? A dictionary of medical eponyms, John Benjamin Murphy

I came across Dr. Isaac George’s name while researching clinical indications for Inhaled Nitric Oxide in June 2013, upon the recent publication of Leaders in Pharmaceutical Business Intelligence FIRST e-Book on  Amazon (Biomed e-Books) [Kindle  Edition]

Perspectives on Nitric Oxide in  Disease  Mechanisms
http://www.amazon.com/dp/B00DINFFYC

Dr. George’s article on Outcomes After Inhaled Nitric Oxide Therapy was particularly useful in my own research on the topic,

Clinical Indications for Use of Inhaled Nitric Oxide (iNO) in the Adult Patient Market: Clinical Outcomes after Use of iNO in the Institutional Market,  Therapy Demand and Cost of Care vs. Existing Supply Solutions

Being myself in Analytics and quantitative model design, 1976-2004, I found of particular interest the range of quantitative methodologies used in the following article by Isaac George, assuming that his days at MIT, came very handy in 2006:

George, Isaac, Xydas, Steve, Topkara, Veli K., Ferdinando, Corrina, Barnwell, Eileen C., Gableman, Larissa, Sladen, Robert N., Naka, Yoshifumi, Oz, Mehmet C.
Clinical Indication for Use and Outcomes After Inhaled Nitric Oxide Therapy
Ann Thorac Surg 2006 82: 2161-2169

As a result of studying this article, I became aware that it has impacted  favorably my 6/2013, Editorial decision, for  a forthcoming book on Cardiovascular Disease in 2013. The Editorial decision regarding the selection and representation of  prominent Cardiothoracic Surgery Theater in the US, and my personal decision to select a Young Cardiothoracic Surgeon

Dr. Isaac George, Assistant Professor of Surgery, Division of Cardiothoracic Surgery, Department of Surgery, New York Presbyterian Hospital/Columbia University Medical Center, New York, NY

Education Profile and Medical Training of a Cardiac Surgeon


Isaac George, MD

Positions and Appointments

2012-present Attending Surgeon, Heart Valve Center
NewYork-Presbyterian Hospital/Columbia University Medical Center, New York, NY
2012-present Assistant Professor of Surgery
Division of Cardiothoracic Surgery, Department of Surgery, New York Presbyterian Hospital/Columbia University Medical Center , New York, NY

Clinical Specialties

Adult aortic and mitral valve surgery
Transcatheter aortic and mitral valve implantation
Hybrid coronary artery bypass surgery
Complex aortic surgery
Complex valvular surgery
Heart failure and transplant surgery
Reoperative cardiac surgery
Thoracic aortic endograft implantation

Research Interests

Director, Cardiac Surgery Research Lab

1. Regulation of myostatin signaling in human cardiomyopathy

2. TGFB regulation in non-syndromic aortic aneurysm formation

3. Valve interstitial cell activation mechanisms after surgical and transcatheter valve replacement

4. Clinical outcomes after valve and hybrid surgery

Education and Training

2011-2012 Interventional Cardiology/Hybrid Cardiac Surgery Fellowship
New York Presbyterian Hospital – Columbia University Medical Center, New York, NY
2011 Ventricular Assist Device/Cardiac Transplant Fellowship, Minimally Invasive, Cardiac Surgery
New York Presbyterian Hospital – Columbia University Medical Center, New York, NY
2009-2011 Fellow, Cardiothoracic Surgery
New York Presbyterian Hospital – Columbia University Medical Center, New York, NY
2008-2009 Post-Doctoral Clinical Fellow, Cardiothoracic Surgery
New York Presbyterian Hospital – Columbia University Medical Center, New York, NY
2006-2008 Resident, General Surgery
New York Presbyterian Hospital – Columbia University Medical Center, New York, NY
2004-2006 Research Fellow, Cardiothoracic Surgery
New York Presbyterian Hospital – Columbia University Medical Center, New York, NY
2002-2004 Resident, General Surgery
New York Presbyterian Hospital – Columbia University Medical Center, New York, NY
2001-2002 Internship, General Surgery
New York Presbyterian Hospital – Columbia University Medical Center, New York, NY
1997-2001 MD, Medicine
Duke University School of Medicine, Durham, NC
1993-1997 BS, Mechanical Engineering
Massachusetts Institute of Technology, Cambridge, MA

Board Certifications

American Board of Thoracic Surgery, 2012-
American Board of Surgery, 2008-
Certification, Pediatric Advanced Life Support, 2008-
Certification, Advanced Trauma Life Support, 2006-
MD, State of New York, 2005-
Certification, Advanced Cardiac Life Support/Basic Life Support, 2001-
United States Medical Licensing Examination Step 3, 2004
United States Medical Licensing Examination Step 2, 2001
United States Medical Licensing Examination Step 1, 2000

Professional Honors

2008 Blakemore Prize – Best Resident Research Award, Columbia University College of Physicians and Surgeons

2007 Blakemore Award – Best Resident Research Award, Columbia University College of Physicians and Surgeons

2006 Blakemore Award – Best Resident Research Award, Columbia University College of Physicians and Surgeons

2004 New Era Cardiac Surgery Conference Scholarship

1995 Pi Tau Sigma, Mechanical Engineering Honor Society

1993 Duke University Comprehensive Cancer Center Fellowship

Professional Societies and Committees

2011 Faculty, Transcatheter Cardiovascular Therapeutics (TCT) Annual Symposium

2010- Candidate Member, Society of Thoracic Surgeons

2010- Fellow-in-Training, American College of Cardiology, Surgeons Council

2005-06 American Society of Artificial Internal Organs

2004- Member, American Heart Association

1997-01 Member, American Medical Association

SOURCE http://asp.cpmc.columbia.edu/facdb/profile_list.asp?uni=ig2006&DepAffil=Surgery

The decision to focus on Cardiothoracic Surgery @Presbeterian as described in Dr. Isaac George’s research had yielded one Sub-Chapter (4.1) in Chapter 4

Cardiac Surgery, Cardiothoracic Surgical Procedures and Percutaneous Coronary Intervention (PCI)/Coronary Angioplasty  – Heart and Cardiovascular Medical Devices in Use in Operating Rooms and in Catheterization Labs in the US

in Volume Three in a forthcoming three volume Series of e-Books on Cardiovascular Diseases

Cardiovascular Diseases: Causes, Risks and Management

This very Sub-Chapter represents milestones in Dr. Isaac George – Becoming a Cardiothoracic Surgeon: An Emerging Profile through Scientific Publications, This profile is now in: 

 

Volume Three

Management of Cardiovascular Diseases

Justin D. Pearlman MD ME PhD MA FACC, Editor

Leaders in Pharmaceutical Business Intelligence, Los Angeles

Aviva Lev-Ari, PhD, RN

Editor-in-Chief BioMed E-Book Series

Leaders in Pharmaceutical Business Intelligence, Boston

avivalev-ari@alum.berkeley.edu

Chapter 5

Invasive Procedures by Surgery versus Catheterization

 

5.1 Cardiothoracic Surgery 

5.1.1 Becoming a Cardiothoracic Surgeon: An Emerging Profile in the Surgery Theater and through Scientific Publications

Aviva Lev-Ari, PhD, RN

5.2: Catheter Interventions

5.2.2 Survivals Comparison of Coronary Artery Bypass Graft (CABG) and Percutaneous Coronary Intervention (PCI) / Coronary Angioplasty

Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

5.3: Transcatheter (Percutaneous) Valves

5.3.1 Transcatheter Aortic Valve Replacement (TAVR): Postdilatation to Reduce Paravalvular Regurgitation During TAVR with a Balloon-expandable Valve

Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

5.3.2 Trans-apical Transcatheter Aortic Valve Replacement in a Patient with Severe and Complex Left Main Coronary Artery Disease (LMCAD)

Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

5.4: Transcatheter (Percutaneous) Pumps

5.4.1  Ventricular Assist Device (VAD): Recommended Approach to the Treatment of Intractable Cardiogentic Shock

Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

5.4.2 Phrenic Nerve Stimulation in Patients with Cheyne-Stokes Respiration and Congestive Heart Failure

Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

Content Analysis of  Surgeon Isaac George, MD – Publications on PubMed

SOURCE

Original classification by Aviva Lev-Ari, PhD, RN, 7/8/2013

Title

Journal

Year

CABG
Stent

Valves
Bio

material
TAVR MVR

End stage

HF

AMI

shock

Congen
Genet

Animal

Model

Heart &
Heart-Lung
Transpl

Stent exteriorization

CCI

13

X

Left Main Coronary

CCI

13

X

TAVR-MVR

JACC

13

X

Paravalvular

CVI

13

X

Cardiogenic Shock

Heart-Lung

12

X

Cheyne-Stokes

Chest

12

X

Myostatin

PlusOne

11

X

Aortic Root & RV

ATS

11

X

Beta-Adrenergic

CV Research

11

X

Erythropoietin

LV  Systolic

J CV

Pharmacol

10

X

Myostatin & HF

Eur J

Heart Failure

10

X

Stentless in valve conduit

ATS

09

X

BNP peptide-

infusion-post MI

Am J Physiol-

Heart Circ

Physiology

09

X

Marginal donor heart

ATS

09

X

Device-surface & Immunogenic

J Thoracic

CV Surg

08

X

Myocardial

electromagnetic

J Cell Physiol

08

X

Clenbuterol-

muscle-mass

J Heart- Lung Transplant

08

X

Bradycardic LV

J Pharmacol Exper Therap

07

X

Ischemia- post

Heart Transplant

J Thoracic

CV Surgery

07

X

Octogen CABG

ATS

07

X

Ventricular synchrony

Eup J Cardio-thoracic Surg

07

X

Inhaled NO

ATS

06

X

X

Adult heart-donor-

to-pediatric

J Thoracic

CV Surg

06

X

Clenbuterol

on LVAD

J Heart-Lung Transplant

06

X

LV-CA stent

Heart Surg

Forum

06

X

LVAD myocarditis

J Thoracic

CV Surg

06

X

MI-Ischemia

Am J Physiol-

Ht-Circ Physiol

06

X

It is the unique combination of Animal Model Research, Biomaterial, Surgical Procedures and Molecular Cardiology, N=33.

Cardiothoracic Surgeon: An Emerging Profile in the Surgery Theater

Isaac George, MD – Clinical Specialties 

  • Adult aortic and mitral valve surgery
  • Transcatheter aortic and mitral valve implantation
  • Hybrid coronary artery bypass surgery
  • Complex aortic surgery
  • Complex valvular surgery
  • Heart failure and transplant surgery
  • Reoperative cardiac surgery
  • Thoracic aortic endograft implantation

 

VIDEOS on CardioThoracic Surgery @ Department of Cardiothoracic Surgery at NewYork-Presbyterian Hospital/Weill Cornell Medical Center in New York City

VIEW VIDEO on the new Heart Center @ Presbyterian Hospital

http://videos.nyp.org/videos/introduction-to-the-vivian-and-seymour-milstein-family-heart-center

VIEW VIDEO on the two Hybrid OR with Siemens Artis Zeego Technology

http://videos.nyp.org/videos/tour-a-hybrid-or-with-siemens-artis-zeego-technology

VIEW VIDEO on Mininally Invesive and Conventional Therapy for Aortic Dissection and Aneurysms – Hybrid Surgery Case

http://videos.nyp.org/videos/thoracic-innovations-in-minimally-invasive-and-conventional-therapy-for-aortic-dissection-and-aneurysms

VIEW VIDEO on Mitral Valve Repair and Replacement – Dr. Karl H. Krieger

Dr. Karl H. Krieger, the Vice Chairman of the Department of Cardiothoracic Surgery at NewYork-Presbyterian Hospital/Weill Cornell Medical Center in New York City, discusses treatment for Mitral Valve Disease. Specifically, Dr. Krieger compares the options of Mitral Valve Repair with Mitral Valve Replacement.

This video with Dr. Krieger is from a web cast at the Ronald O. Perelman Heart Institute at NewYork-Presbyterian.

VIEW VIDEO on Left Ventricular Assist Devices (LVADs) – Dr. Jonathan Chen

Dr. Jonathan Chen, the Site Chief for Pediatric Cardiac Surgery at NewYork-Presbyterian Hospital/Weill Cornell Medical Center in New York City, explains how Left Ventricular Assist Devices (LVADs) work and how they can benefit patients with heart failure.

LVADs are implantable devices that help the heart pump blood. They can be used as a temporary therapy, allowing patients’ hearts to rest while they recover from cardiac events such as heart attacks, or while they wait for hearts to become available for transplants. For some patients whose hearts are unlikely to recover and are not candidates for heart transplants, the devices may be used as a permanent therapy. Heart failure, especially in severe forms, can force patients to lead restricted lives because often even very limited physical activity, such as walking from one room to another, will leave them breathless.

Dr. Chen is a pediatric cardiothoracic surgeon, yet the information in the video is applicable to adult patients as well.

VIEW VIDEO on Transcatheter Aortic Valve Implantation @ Presbyterian Hospital

http://videos.nyp.org/videos/chapter-3-transcatheter-aortic-valve-implantation

Heart, Heart-Lung Transplantation @ Presbyterian Hospital

Organ transplantation that prolongs and dramatically improves quality of life is nearly a daily occurrence at Columbia University Medical Center.

The success of solid organ transplantation – with improved surgical techniques, replacement organ procurement, and medical management – is advancing each year. Many of these advances have resulted from scientific and clinical research conducted at Columbia University Medical Center.

A Brief History of Transplantation at Columbia

Transplantation: Where we’ve been, where we’re going

Transplantation: Where we've been, where we're going
Eric A. Rose, MD, former chairman of the department of surgery, left center, performing the first successful pediatric heart transplant in 1984. Transplant pioneer Keith Reemtsma, MD, who is overseeing the operating field (top of photo).

When he transplanted a chimpanzee kidney into a human patient in the late 1960’s, the late Keith Reemtsma, MD, then Department of Surgery Chairman at Tulane University, revolutionized treatment of end-stage organ failure and initiated an era of unprecedented exploration into organ transplantation that would affect the lives of patients around the world.

Transferring to Columbia-Presbyterian Medical Center in 1971, Dr. Reemtsma recruited Mark A. Hardy, MD, who laid another cornerstone of organ transplant medicine by founding the program for dialysis and kidney transplantation. Dr. Hardy based the new program on the principle of collaborative clinical care between surgeons and nephrologists. During a time when renal transplant programs were managed by one or the other discipline but never by both simultaneously, the medical community regarded the concept as folly. Yet the program grew steadily, as did the program’s immune tolerance research initiatives to induce the transplant recipient’s body to accept a donor organ. This multidisciplinary cooperation also led to major contributions in immunogenetics, immunosuppression, and treatment of autoimmune diseases and lymphoma — and it ultimately became the overarching principle for all the NewYork-Presbyterian Hospital transplant services.

Mark A. Hardy, MD

Mark Hardy
Eric Rose
Eric A. Rose, MD
Lloyd Ratner
Lloyd E. Ratner, MD

Colleagues universally give credit to Eric A. Rose, MD, who co-founded the heart transplantation program with Dr. Reemtsma, for his successful transformation of the program into the outstanding center it is today. A parade of achievements marks the history of the heart transplant program, including the first mechanical bridge-totransplantation using intra-aortic balloon pumps in the 1970’s, and the first successful pediatric heart transplant, performed by Dr. Rose in 1984. Under the guidance of Dr. Rose and his successors, the program has pioneered research in immunosuppressant medications, mechanical assist devices, and minimally invasive surgical procedures. It currently performs over 100 heart transplants yearly, with among the highest success rates in the nation.

Also in 2004, Lloyd E. Ratner, MD, succeeded Dr. Hardy as director of the renal and pancreas transplant program. One of the first to perform laparoscopic donor operations, Dr. Ratner has found creative solutions to overcome immune barriers to kidney transplantation. The program now routinely uses extended-criteria donor organs, performs transplants among incompatible donors, and is a leader in coordinating “donor swaps” to maximize availability of compatible donor organs. Since Dr. Ratner’s arrival, Columbia has been designated one of ten regional islet resource centers in the U.S. that isolate and transplant pancreatic cells to treat type 1 diabetes as part of a limited protocol controlled by the FDA. Recent progress in visualization of pancreatic islets using PET technology, under the guidance of Paul Harris, PhD, has been recognized by the scientific community as a milestone in this developing field.

NYPH/Columbia received UNOS approval for pancreatic transplantation in January 2008. Our premier kidney transplant program is facilitating rapid growth of the new pancreatic transplantation program, which overlaps both in its patient population and its surgical and medical expertise. The northeast region of the U.S. has been consistently underserved as far as access to pancreatic transplantation, with relatively few centers serving a disproportionately large metropolitan population. The expanding program at NewYork-Presbyterian now provides much-needed access to patients with end-stage pancreatic disease in New York state, particularly those with the most complex medical and surgical challenges.

Transplantation of cells, rather than organs, is emerging as a therapy with enormous potential. Transplantation of either a patient’s own or a foreign donor’s bone marrow cells, for example, offers hope of regenerating the heart so that patients with heart failure may be able to avoid heart transplantation.

In introducing the transplantation programs, it would be remiss to neglect mention of the yet another dimension in which they excel — education. Physician training is a top priority, and NYPH/Columbia has trained many of the greatest transplant surgeons over the last 20 years, including many of the leaders of transplant programs throughout the U.S.

http://columbiasurgery.org/transplant/history.html

Transplant Initiative

At NewYork-Presbyterian Hospital/Columbia University Medical Center, the Transplant Initiative (TI) has been launched to drive the growth of both clinical and research aspects of transplantation. This multi-year undertaking will involve Departments of Medicine, Pathology, Pediatrics, and Surgery and all of the solid organ transplantation programs, both adult and pediatrics. It is led by its Executive Director, Jean C. Emond, MD.

Although NYP/Columbia is already a national leader in clinical transplantation with respect to volume and patient outcomes, this initiative will further leverage the diverse expertise of its transplant scientists and clinicians.

Heart Transplantation

Approximately 2,200 heart transplants are now performed each year in more than 150 heart transplant centers in the United States. The surgeons and cardiologists of Columbia University Medical Center of NYPH have a long and distinguished history of advancing “standards of care” and the survival rates of our patients by using innovative surgical techniques, by applying our basic scientific research in immunosuppression to the clinical setting, and by inventing and perfecting life-sustaining cardiac assist devices that prolong life while waiting for organ availability.

Lung and Heart-Lung Transplantation

Columbia University Medical Center’s lung and heart-lung transplantation program, which began in 1985, is fast approaching its 200th transplant. Performing more than 30 transplants each year, the lung and heart-lung transplant teams have earned a national reputation for excellence. Our world-renowned transplantation researchers have helped lead the way to improvements in care that, nationwide, have increased the long-term survival rate for lung transplantation by 50% over the past seven years. Among those improvements are new immunosuppressive agents, new antibiotics, refined surgical techniques, and a more comprehensive understanding of follow-up care.

http://columbiasurgery.org/transplant/

It is the combination of basic research at the molecular cardiology level, biomaterial, surgical procedures and PUBLICATION of Cases and research results that found me in Dr. George’s territory as a renewed inspiration.

For Author’s training & experience @ MGH – Cardiac Floor – Ellison 11, BWH – CCU, Tower 3 – 12Fl, BIDMC – Acute Surgery, Farr 9, and Texas Heart Institute, Perfusion, Faulkner Hospital – ICU

https://pharmaceuticalintelligence.com/founder/scientific-and-medical-affairs-chronological-cv/

and in Part II, Section IV in

https://pharmaceuticalintelligence.com/2013/07/14/vascular-surgery-position-statement-in-2013-and-contributions-of-a-vascular-surgeon-at-peak-career-richard-paul-cambria-md-chief-division-of-vascular-and-endovascular-surgery-co-director-thoracic/

Surgeon Isaac George, MD – Training in the OR @ Presbyterian Hospital

2011-2012 Interventional Cardiology/Hybrid Cardiac Surgery Fellowship
New York Presbyterian Hospital – Columbia University Medical Center, New York, NY
2011 Ventricular Assist Device/Cardiac Transplant Fellowship, Minimally Invasive, Cardiac Surgery
New York Presbyterian Hospital – Columbia University Medical Center, New York, NY
2009-2011 Fellow, Cardiothoracic Surgery
New York Presbyterian Hospital – Columbia University Medical Center, New York, NY
2008-2009 Post-Doctoral Clinical Fellow, Cardiothoracic Surgery
New York Presbyterian Hospital – Columbia University Medical Center, New York, NY
2006-2008 Resident, General Surgery
New York Presbyterian Hospital – Columbia University Medical Center, New York, NY
2004-2006 Research Fellow, Cardiothoracic Surgery
New York Presbyterian Hospital – Columbia University Medical Center, New York, NY
2002-2004 Resident, General Surgery
New York Presbyterian Hospital – Columbia University Medical Center, New York, NY
2001-2002 Internship, General Surgery
New York Presbyterian Hospital – Columbia University Medical Center, New York, NY

SOURCE

http://asp.cpmc.columbia.edu/facdb/profile_list.asp?uni=ig2006&DepAffil=Surgery

Surgeon Isaac George, MD – Publications on PubMed

http://www.ncbi.nlm.nih.gov/pubmed

Select item 234757651.

Stent exteriorization facilitates surgical repair for large-bore sheath complications.

George I, Shrikhande G, Williams MR.

Catheter Cardiovasc Interv. 2013 Mar 8. doi: 10.1002/ccd.24918. [Epub ahead of print]

PMID:

 23475765

[PubMed – as supplied by publisher]

Related citations

Select item 234131722.

Management of significant left main coronary disease before and after trans-apical transcatheter aortic valve replacement in a patient with severe and complex arterial disease.

Paradis JM, George I, Kodali S.

Catheter Cardiovasc Interv. 2013 Feb 14. doi: 10.1002/ccd.24865. [Epub ahead of print]

PMID:

 23413172

[PubMed – as supplied by publisher]

Related citations

Select item 233478683.

Concomitant transcatheter aortic and mitral valve-in-valve replacements using transfemoral devices via the transapical approach: first case in United States.

Paradis JM, Kodali SK, Hahn RT, George I, Daneault B, Koss E, Nazif TM, Leon MB, Williams MR.

JACC Cardiovasc Interv. 2013 Jan;6(1):94-6. doi: 10.1016/j.jcin.2012.07.018. No abstract available.

PMID:

 23347868

[PubMed – in process]

Related citations

Select item 233398414.

Efficacy and safety of postdilatation to reduce paravalvular regurgitation during balloon-expandable transcatheter aortic valve replacement.

Daneault B, Koss E, Hahn RT, Kodali S, Williams MR, Généreux P, Paradis JM, George I, Reiss GR, Moses JW, Smith CR, Leon MB.

Circ Cardiovasc Interv. 2013 Feb;6(1):85-91. doi: 10.1161/CIRCINTERVENTIONS.112.971614. Epub 2013 Jan 22.

PMID:

 23339841

[PubMed – in process]

Related citations

Select item 226080345.

A stepwise progression in the treatment of cardiogenic shock.

Pollack A, Uriel N, George I, Kodali S, Takayama H, Naka Y, Jorde U.

Heart Lung. 2012 Sep-Oct;41(5):500-4. doi: 10.1016/j.hrtlng.2012.03.007. Epub 2012 May 16.

PMID:

 22608034

[PubMed – indexed for MEDLINE]

Related citations

Select item 223022996.

Transvenous phrenic nerve stimulation in patients with Cheyne-Stokes respiration and congestive heart failure: a safety and proof-of-concept study.

Zhang XL, Ding N, Wang H, Augostini R, Yang B, Xu D, Ju W, Hou X, Li X, Ni B, Cao K, George I, Wang J, Zhang SJ.

Chest. 2012 Oct;142(4):927-34.

PMID:

 22302299

[PubMed – in process]

Related citations

Select item 219316167.

Myostatin is elevated in congenital heart disease and after mechanical unloading.

Bish LT, George I, Maybaum S, Yang J, Chen JM, Sweeney HL.

PLoS One. 2011;6(9):e23818. doi: 10.1371/journal.pone.0023818. Epub 2011 Sep 13.

PMID:

 21931616

[PubMed – indexed for MEDLINE]

Free PMC Article

Related citations

Select item 216199558.

Aortic root and right ventricular outflow tract reconstruction using composite biological valved conduits after failed Ross procedure.

Russo MJ, Easterwood R, Williams MR, George I, Stewart AS.

Ann Thorac Surg. 2011 Jun;91(6):e87-9. doi: 10.1016/j.athoracsur.2011.01.035.

PMID:

 21619955

[PubMed – indexed for MEDLINE]

Related citations

Select item 214937019.

β-adrenergic receptor blockade reduces endoplasmic reticulum stress and normalizes calcium handling in a coronary embolization model of heart failure in canines.

George I, Sabbah HN, Xu K, Wang N, Wang J.

Cardiovasc Res. 2011 Aug 1;91(3):447-55. doi: 10.1093/cvr/cvr106. Epub 2011 Apr 14.

PMID:

 21493701

[PubMed – indexed for MEDLINE]

Free Article

Related citations

Select item 2088161410.

Erythropoietin derivate improves left ventricular systolic performance and attenuates left ventricular remodeling in rats with myocardial infarct-induced heart failure.

Xu K, George I, Klotz S, Hay I, Xydas S, Zhang G, Cerami A, Wang J.

J Cardiovasc Pharmacol. 2010 Nov;56(5):506-12. doi: 10.1097/FJC.0b013e3181f4f05a.

PMID:

 20881614

[PubMed – indexed for MEDLINE]

Related citations

Select item 2034855011.

Myostatin activation in patients with advanced heart failure and after mechanical unloading.

George I, Bish LT, Kamalakkannan G, Petrilli CM, Oz MC, Naka Y, Sweeney HL, Maybaum S.

Eur J Heart Fail. 2010 May;12(5):444-53. doi: 10.1093/eurjhf/hfq039. Epub 2010 Mar 27.

PMID:

 20348550

[PubMed – indexed for MEDLINE]

Free PMC Article

Related citations

Select item 1993228712.

Stentless bioprosthesis in a valved conduit: implications for pulmonary reconstruction.

George I, Shah JN, Bacchetta M, Stewart A.

Ann Thorac Surg. 2009 Dec;88(6):2022-4. doi: 10.1016/j.athoracsur.2009.04.145.

PMID:

 19932287

[PubMed – indexed for MEDLINE]

Related citations

Select item 1985873513.

Long-term effects of B-type natriuretic peptide infusion after acute myocardial infarction in a rat model.

George I, Xydas S, Klotz S, Hay I, Ng C, Chang J, Xu K, Li Z, Protter AA, Wu EX, Oz MC, Wang J.

J Cardiovasc Pharmacol. 2010 Jan;55(1):14-20. doi: 10.1097/FJC.0b013e3181c5e743.

PMID:

 19858735

[PubMed – indexed for MEDLINE]

Free PMC Article

Related citations

Select item 1952537314.

Prolonged effects of B-type natriuretic peptide infusion on cardiac remodeling after sustained myocardial injury.

George I, Morrow B, Xu K, Yi GH, Holmes J, Wu EX, Li Z, Protter AA, Oz MC, Wang J.

Am J Physiol Heart Circ Physiol. 2009 Aug;297(2):H708-17. doi: 10.1152/ajpheart.00661.2008. Epub 2009 Jun 12.

PMID:

 19525373

[PubMed – indexed for MEDLINE]

Free PMC Article

Related citations

Select item 1932412915.

Matching high-risk recipients with marginal donor hearts is a clinically effective strategy.

Russo MJ, Davies RR, Hong KN, Chen JM, Argenziano M, Moskowitz A, Ascheim DD, George I, Stewart AS, Williams M, Gelijns A, Naka Y.

Ann Thorac Surg. 2009 Apr;87(4):1066-70; discussion 1071. doi: 10.1016/j.athoracsur.2008.12.020.

PMID:

 19324129

[PubMed – indexed for MEDLINE]

Free PMC Article

Related citations

Select item 1854438916.

Association of device surface and biomaterials with immunologic sensitization after mechanical support.

George I, Colley P, Russo MJ, Martens TP, Burke E, Oz MC, Deng MC, Mancini DM, Naka Y.

J Thorac Cardiovasc Surg. 2008 Jun;135(6):1372-9. doi: 10.1016/j.jtcvs.2007.11.049.

PMID:

 18544389

[PubMed – indexed for MEDLINE]

Related citations

Select item 1844681617.

Myocardial function improved by electromagnetic field induction of stress protein hsp70.

George I, Geddis MS, Lill Z, Lin H, Gomez T, Blank M, Oz MC, Goodman R.

J Cell Physiol. 2008 Sep;216(3):816-23. doi: 10.1002/jcp.21461.

PMID:

 18446816

[PubMed – indexed for MEDLINE]

Free PMC Article

Related citations

Select item 1837488418.

Clenbuterol increases lean muscle mass but not endurance in patients with chronic heart failure.

Kamalakkannan G, Petrilli CM, George I, LaManca J, McLaughlin BT, Shane E, Mancini DM, Maybaum S.

J Heart Lung Transplant. 2008 Apr;27(4):457-61. doi: 10.1016/j.healun.2008.01.013.

PMID:

 18374884

[PubMed – indexed for MEDLINE]

Related citations

Select item 1727719619.

Bradycardic therapy improves left ventricular function and remodeling in dogs with coronary embolization-induced chronic heart failure.

Cheng Y, George I, Yi GH, Reiken S, Gu A, Tao YK, Muraskin J, Qin S, He KL, Hay I, Yu K, Oz MC, Burkhoff D, Holmes J, Wang J.

J Pharmacol Exp Ther. 2007 May;321(2):469-76. Epub 2007 Feb 2.

PMID:

 17277196

[PubMed – indexed for MEDLINE]

Free Article

Related citations

Select item 1725859920.

The effect of ischemic time on survival after heart transplantation varies by donor age: an analysis of the United Network for Organ Sharing database.

Russo MJ, Chen JM, Sorabella RA, Martens TP, Garrido M, Davies RR, George I, Cheema FH, Mosca RS, Mital S, Ascheim DD, Argenziano M, Stewart AS, Oz MC, Naka Y.

J Thorac Cardiovasc Surg. 2007 Feb;133(2):554-9.

PMID:

 17258599

[PubMed – indexed for MEDLINE]

Related citations

Discharge to home rates are significantly lower for octogenarians undergoing coronary artery bypass graft surgery.

Bardakci H, Cheema FH, Topkara VK, Dang NC, Martens TP, Mercando ML, Forster CS, Benson AA, George I, Russo MJ, Oz MC, Esrig BC.

Ann Thorac Surg. 2007 Feb;83(2):483-9.

PMID:

 17257973

[PubMed – indexed for MEDLINE]

Related citations

Select item 1712612922.

Clinical indication for use and outcomes after inhaled nitric oxide therapy.

George I, Xydas S, Topkara VK, Ferdinando C, Barnwell EC, Gableman L, Sladen RN, Naka Y, Oz MC.

Ann Thorac Surg. 2006 Dec;82(6):2161-9.

PMID:

 17126129

[PubMed – indexed for MEDLINE]

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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.
 
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.

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)

https://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)
https://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)
https://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)
https://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)
https://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)
https://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)
https://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)

https://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)
https://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)

https://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)
https://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)
https://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)
https://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)
https://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)
https://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 mo...

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 m...

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

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

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Nitric Oxide and it’s impact on Cardiothoracic Surgery

Author, curator: Tilda Barliya PhD

 

In the past few weeks we’ve had extensive in-depth series about nitric oxide (NO) and it’s role in renal function and donors in renal disorders, coagulation, endothelium and hemostasis. This inspired this new post regarding the impact of NO on cardiothoratic surgery.  You can read and follow up on these posts here: https://pharmaceuticalintelligence.com/category/nitric-oxide-in-health-and-disease/

Atherosclerosis in the form of peripheral arterial disease (PAD) affects approximately eight million Americans, which includes 12 to 20% of individuals over the age of 65.  Approximately 20% of patients with PAD have typical symptoms of lower extremity claudication, rest pain, ulceration, or gangrene, and one-third have atypical exertional symptoms. Persons with PAD have impaired function and quality of life even if they do not report symptoms and experience a decline in lower extremity function over time. Cardiovascular disease is the major cause of death in patients with intermittent claudication; the annual rate of cardiovascular events (myocardial infarction, stroke, or death from cardiovascular causes) is 5 to 7%.  Thus, PAD represents a significant source of morbidity and mortality. (1) (http://www.medscape.com/viewarticle/569812).

Several options exist for treating atherosclerotic lesions, including:

  • percutaneous transluminal angioplasty with and without stenting,
  • endarterectomy
  • bypass grafting

Unfortunately, patency rates for each of these procedures continue to be suboptimal secondary to the development of neointimal hyperplasia. A universal feature of all vascular surgical procedures is the removal of or damage to the endothelial cell monolayer that occurs whether the procedure performed is endovascular or open. This endothelial damage leads to a decreased or absent production of nitric oxide (NO) at the site of injury.

noendoschematic

he relationship between NO and the cardiovascular system has proven to be a landmark discovery, and the scientists credited for its discovery were awarded the Nobel Prize in Medicine in 1998. Since its discovery, NO has proven to be one of the most important molecules in vascular homeostasis. In fact, the term endothelial dysfunction has now become synonymous with the reduced biologic activity of NO.

NO produced by endothelial cells has been shown to have many beneficial effects on the vasculature.

As described above,

  • NO stimulates vascular smooth muscle cells (VSMC) relaxation, which leads to vessel vasodilatation.  
  • NO has opposite beneficial affects on endothelial cells compared with VSMCs.
  • Whereas NO stimulates endothelial cell proliferation and prevents endothelial cell apoptosis,  it inhibits VSMC growth and migration  and stimulates VSMC apoptosis.  
  • NO also has many thromboresistant properties, such as inhibition of platelet aggregation, adhesion, and activation;  inhibition of leukocyte adhesion and migration;  and inhibition of matrix formation

 As stated before, the endothelial cell monolayer is often removed or damaged during the time of vascular procedures, which leads to a local decrease in the production of NO. It is now understood that this loss of local NO synthesis by endothelial cells at the site of vascular injury is one of the inciting events that allows platelet aggregation, inflammatory cell infiltration, and VSMC proliferation and migration to occur in excess, which, taken together, leads to neointimal hyperplasia.

Reendothelialization of the injured artery can restore proper function to the artery and potentially halt the restenotic process. Many studies have attempted to improve the patency of bypass grafts and stents by coating them with endothelial cells in the hope that this would restore the thromboresistant nature of native blood vessels.

Unfortunately, although it has been possible to coat these devices with endothelial cells, these cells do not behave like normal endothelial cells and their NO production is often diminished or absent. Because the vasoprotective properties of endothelial cells are largely carried out by NO alone, investigators are engaged in research to improve the bioavailability of NO at the site of vascular injury in an attempt to reduce the risk of thrombosis and restenosis after successful revascularization. The overall goal of using a NO-based approach is to reproduce the same thromboresistive moiety observed with normal NO production.

Why of delivering NO to the injured site:

  • Systemic delivery
  • Local delivery

Systemic Delivery

One simple mechanism by which to deliver NO to the body is via inhalational therapy. Inhaled NO has been used clinically in the past to selectively reduce pulmonary vascular resistance in patients with pulmonary hypertension, as well as a potential therapy for patients with acute respiratory distress syndrome. Because the gas is delivered only to the pulmonary system and has a very short half-life, it was thought that there would be no systemic effects of the drug. Subsequently, studies in the mid- to late 1990s suggested that inhaled NO had beneficial antiplatelet and antileukocyte properties without adverse systemic side effects (2,3)

To test if inhaled NO had any beneficial systemic properties specifically on the vasculature, Lee and colleagues evaluated the effect of inhaled NO on neointimal hyperplasia in rats undergoing carotid balloon injury, Unfortunately, the treatment was required for the full 2 weeks to see any difference between the treatment and the control group, thereby limiting its clinical utility.

Despite some of the early animal studies, investigations with healthy human volunteers failed to reproduce these findings.I t was speculated that despite the obvious effects of inhaled NO on the pulmonary vasculature, systemic bioavailability could not be reliably achieved because of the immediate binding and depletion of NO by hemoglobin as soon as it entered the systemic circulation.

Hamon and colleagues tested the ability of orally supplementing l-arginine (2.25%), the precursor to NO, in the drinking water of rabbits to reduce the formation of neointimal hyperplasia after injuring the iliac arteries with a balloon.  This amount of l-arginine is approximately sixfold higher than normal daily intake. When the arteries were studied 4 weeks after injury, the l-arginine-fed group exhibited less neointimal hyperplasia and greater acetylcholine-induced relaxation compared with the control animals. The authors speculated that the improved outcomes were due to increased bioavailability of NO secondary to the l-arginine-supplemented diets. To test the ability of this supplemented diet to reduce neointimal hyperplasia in a vein bypass graft model, Davies and colleagues fed rabbits l-arginine (2.25%) 7 days prior to and 28 days after common carotid vein bypass grafts. A 51% decrease in the formation of neointimal hyperplasia was demonstrated in the l-arginine-fed groups, and their vein grafts exhibited preserved NO-mediated relaxation.

Despite some of the positive findings in animals, similar studies in humans have failed to show any benefit with l-arginine supplementation. Shiraki and colleagues studied the effects of short-term high-dose l-arginine on restenosis after PTCA.  Thirty-four patients undergoing cardiac catheterization and PTCA for angina pectoris received 500 mg of l-arginine administered through the cardiac catheter immediately prior to PTCA and 30 g per day of l-arginine administered via the peripheral vein for 5 days after PTCA. No significant statistical differences in restenosis were observed between the two groups (34% vs 44%). The authors speculated that the lack of effect was secondary to the fact that although the levels of l-arginine in the plasma increased significantly, NO and cyclic guanosine monophosphate (cGMP) did not. (4)

Table 1.  Comparison of Different Nitric Oxide Donor Drugs Currently Used for Clinical or Research Purposes
Drug Mechanism of NO Release Unique Properties
Diazeniumdiolates Spontaneous when in contact with physiologic fluidsNO release follows first-order kinetics Stable as solidsVarious reliable half-lives depending on the structure of the nucleophile it is attached to
Nitrosamines can form as by-products
S-Nitrosothiols Copper ion-mediated decomposition Stable as a solid
Direct reaction with ascorbate Must be protected from light
Homeolytic cleavage by light Present in circulating blood
Potential for unlimited NO release
Sydnonimines Requires enzymatic cleavage by liver esterases to form active metabolite Stable as a solidMust be protected from light
Requires molecular oxygen as an electron acceptor Requires alkaline pHReleases superoxide as a by-product, which may have negative effects
l-Arginine Substrate for NOS genes Stable as a solid
Ease of administration
Dependent on presence of NOS for NO production
Sodium nitroprusside Requires a one-electron reduction to release NO Stable as a solid
Must be protected from light
Light can induce NO release Must be given intravenously
Releases cyanide as a by-product
Organic nitrates Either by enzymatic cleavage or nonenzymatic bioactivation with sulfhydryl or thiol groups Stable as a solid
Must be protected from light
Ease of administration
Development of tolerance limits efficacy
NO-releasing aspirin Require enzymatic cleavage to break the covalent bond between the aspirin and the NO moiety Stable as a solid
Ease of administration
Inherent benefits of aspirin also
Does not affect systemic blood pressure

Despite the ease of administration, the reliability of drug delivery, and the relative safety of these NO-donating drugs, there are limitations associated with systemic administration. One such limitation is that NO is rapidly inactivated by hemoglobin in the circulating blood, resulting in limited bioavailability. Furthermore, in attempts to increase the amount of drug delivered to obtain the desired clinical effect, unwanted systemic circulatory effects (eg, vasodilation) and unwanted hemostatic effects (eg, bleeding) often preclude administration of biologically effective doses of NO.

Because NO produces systemic side effects, lower doses of NO have been used in many of the human studies. One of the reasons for the differences observed between the animal studies and the human studies was the 10- to 50-fold lower doses of drugs used in the human studies compared with the animal studies. Thus, local delivery of NO may achieve improved results.

Local Delivery

The local delivery of drugs allows for the administration of the maximally effective dose of a drug without the unwanted systemic side effects. Because the target vessels are easily accessible during most vascular procedures, a local pharmacologic approach to administer a drug during the intervention can be easily performed.

Suzuki and colleagues performed a prospective, randomized, single-center clinical trial. (7)

The study population consisted of patients with symptomatic ischemic heart disease who were undergoing coronary artery stent placement. After stent deployment, l-arginine (600 mg/6 mL) or saline (6 mL) was locally delivered via a catheter over 15 minutes. The patients were followed with serial angiography and intravascular ultrasonography to assess for neointimal thickness for up to 6 months. The authors found that in the l-arginine-treated groups, there was slightly less neointimal volume, but this was not statistically significant.

Because it was not known if the addition of l-arginine actually translated to increased NO production, several studies have focused on the addition of NO donors directly to the site of injury.However, Critics of some of the highlighted animal studies point out that the evaluation of neointimal hyperplasia was performed radiographically, which could be subjectively biased. Furthermore, infusing the drug through a catheter for an extended period of time during the procedure to achieve an effect is not clinically feasible. Because of this, other studies have aimed to develop a clinically applicable approach to deliver NO locally to the site of injury.

  • Hydrogels
  • Vascular grafts
  • Gene therapy

represents another method by which to locally increase the level of NO at the site of vascular injury, tested in different multiple creative animal models. Thought, most of this studies shown great preliminary results, only the gene therapy moved forward into randomized clinical trial in humans using gene therapy to reduce neointimal hyperplasia.

In December 2000, the Recombinant DNA Advisory Committee at the National Institutes of Health voted unanimously to proceed with the first phase of clinical evaluation of iNOS lipoplex-mediated gene transfer, called REGENT-1: Restenosis Gene Therapy Trial. (8). The primary objective of this multicenter, prospective, single-blind, dose escalation study was to obtain safety and tolerability information of iNOS-lipoplex gene therapy for reducing restenosis following coronary angioplasty. As of 2002, 27 patients had been enrolled overseas and the process had been determined to be safe. To date, no results have been published as it appears that this trial lost its funding and closed. On April 5, 2002, a notification was issued that the trial had been closed without enrolling any individuals in the United States.

Unfortunately, despite the promising findings shown with NOS therapy, the field of gene therapy has been mottled by two widely known complications. One case occurred as the result of administering a large viral load that led to the death of a patient. In addition, in France, there were at least two cases of malignancy following retroviral gene therapy.  (9)

Summary

Atherosclerosis in the form of coronary artery disease and peripheral vascular disease continues to be a major source of morbidity and mortality. Unfortunately, the procedures and materials that are currently used to alleviate these disease states are temporary at best because of the inevitable injury to the native endothelium and the subsequent impairment of NO release. Since the discovery of NO and its role in vascular biology, a main focus in vascular research has been to create novel mechanisms to use NO to combat neointimal hyperplasia. To date, numerous animal studies have restored NO production to the vasculature and have shown that this inhibits neointimal hyperplasia, improves patency rates, and is safe to the animal. Clinical studies using these novel NO-releasing compounds in humans are on the horizon.

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8. von der Leyen HE, Chew N. Nitric oxide synthase gene transfer and treatment of restenosis: from bench to bedside Eur J Clin Pharmacol 2006;62:83-89

9.  Barbato JE, Tzeng E. iNOS gene transfer for graft disease Trends Cardiovasc Med 2004;14:267-72.

10. E. Matevossian, A. Novotny, C. Knebel, T. Brill, M. Werner, I. Sinicina, M. Kriner, M. Stangl, S. Thorban, and N. Hüser. The Effect of Selective Inhibition of Inducible Nitric Oxide Synthase on Cytochrome P450 After Liver Transplantation in a Rat Model. Transplantation Proceedings 2008, 40, 983–985. http://211.144.68.84:9998/91keshi/Public/File/29/40-4/pdf/1-s2.0-S0041134508004181-main.pdf

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