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Robert Burgess Jennings

James B. Duke Distinguished Professor Emeritus of Medicine
Pathology
Box 3712 Med Ctr, Durham, NC 27710
409 Elf St, Durham, NC 27705

Overview


RESEARCH ABSTRACT of Robert B Jennings.

Our main research effort is aimed at learning the molecular event or series
of events that causes myocytes exposed to ischemia to die. We have established that sarcolemma disruption is the event that causes myocyte death and are in the process or trying to learn the cause of sarcolemma disruption. Our current studies are aimed chiefly at understanding the metabolic changes developing in ischemic myocardium during the phase of reversible injury.

Our chief accomplishment in the last few years has been the discovery of a
new phenomenon termed ischemic preconditioning. We have shown that myocardium exposed to a brief episode of ischemia and reperfusion will tolerate a much longer episode of sustained ischemia than virgin myocardium. This is a very striking protective effect and has become the subject of intense investigation throughout the world. At the November 1996 American Heart meeting, there were several hundred abstracts on this topic. This is surprising since we first described it in 1986.

At the present time, we are concentrating on learning the mechanism
underlying preconditioning. Our current working hypothesis is that preconditioning is due to a reduction in energy demand occurring during the sustained episode of ischemia. We propose that the reduced demand results from stimulation of A1 receptors by adenosine released into the interstitial space during the preconditioning episode of ischemia. These receptors, via Gi protein, activate protein kinase C to phosphorylate an unknown protein or proteins and thereby reduce energy consumption. We think that the protein phosphorylated is the KATP channel which opens when the level of cellular ATP declines. In the phosphorylated state, we propose that it stays open. The result is increased exit of K+ during ischemia, in effect local cardioplegia and improved tolerance to ischemia.

Using the pig heart we also are investigating the mechanism underlying the cardiotoxicity of diaspora cross-linked human hemoglobin. Vasospasm appears to be the most likely cause of the cardiac necrosis but O(2) derived free radicals also are possible.

Current Appointments & Affiliations


James B. Duke Distinguished Professor Emeritus of Medicine · 2003 - Present Pathology, Clinical Science Departments
Professor Emeritus of Pathology · 2003 - Present Pathology, Clinical Science Departments

Recent Publications


Roles of collateral arterial flow and ischemic preconditioning in protection of acutely ischemic myocardium.

Journal Article J Electrocardiol · 2014 The extent and rate at which necrosis develops in experimental acute myocardial infarction in the dog heart is presented together with an analysis of the role played by protective mechanisms in myocyte death. Preconditioning with ischemia delays but does n ... Full text Link to item Cite

Commentary on selected aspects of cardioprotection.

Conference J Cardiovasc Pharmacol Ther · 2011 Three aspects of cardioprotection are discussed in this article. The first is myocyte death as a function of the duration and severity of ischemia in experimental acute myocardial infarction in the dog heart. The short period of time during which reperfusi ... Full text Link to item Cite

Metabolism of preconditioned myocardium: effect of loss and reinstatement of cardioprotection.

Journal Article J Mol Cell Cardiol · September 2001 Ischemic preconditioning is associated with slower destruction of the adenine nucleotide pool and a slower rate of anaerobic glycolysis during subsequent ischemic stress. Whether this association is causal is uncertain. Using metabolite levels found at bas ... Full text Link to item Cite
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Recent Grants


Myocardial Ischemia and Reperfusion

ResearchCo-Principal Investigator · Awarded by National Institutes of Health · 1990 - 2001

Myocardial Ischemia And Reperfusion

ResearchCo-Principal Investigator · Awarded by National Institutes of Health · 1996 - 1999

Myocardial Ischemia

ResearchPrincipal Investigator · Awarded by National Institutes of Health · 1978 - 1997

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Education, Training & Certifications


Northwestern University · 1949 M.D.