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Metabolic plasticity and the promotion of cardiac protection in ischemia and ischemic preconditioning.

Abstract：

:The concept of metabolic protection of the ischemic myocardium is in constant evolution and has recently been supported by clinical studies. Historically, enhanced glucose metabolism and glycolysis were proposed as anti-ischemic cardioprotection. This hypothesis is supported by the sub-cellular linkage between key glycolytic enzymes and the activity of two survival-promoting membrane-bound pumps, namely the sodium-potassium ATPase, and the calcium uptake pump of the sarcoplasmic reticulum. Moreover, improved resistance against ischemia follows the administration of glucose-insulin-potassium in a variety of animal models and in patients following acute myocardial infarction. The metabolic plasticity paradigm has now been expanded to include (1) the benefit of improved coupling of glycolysis to glucose oxidation, which explains the action of anti-ischemic fatty acid inhibitors such as trimetazidine and ranolazine; (2) the role of malonyl CoA in the glucose-fatty acid interaction; and (3) the anti-apoptotic role of insulin. Furthermore, we argue for a protective role of increased glucose uptake in the preconditioning paradigm. Additionally, we postulate an adaptive role of mitochondrial respiration in the promotion of cardioprotection in the context of ischemic preconditioning. The mechanisms driving these mitochondrial perturbations are still unknown, but are hypothesized to involve an initial modest uncoupling of respiration from the production of mitochondrial ATP. These perturbations are in turn thought to prime the mitochondria to augment mitochondrial respiration during a subsequent ischemic insult to the heart. In this review we discuss studies that demonstrate how metabolic plasticity can promote cardioprotection against ischemia and reperfusion injury and highlight areas that require further characterization.

journal_name

J Mol Cell Cardiol

journal_title

Journal of molecular and cellular cardiology

authors

Opie LH,Sack MN

doi

10.1006/jmcc.2002.2066

keywords:

subject

Has Abstract

pub_date

2002-09-01 00:00:00

pages

1077-89

issue

eissn

0022-2828

issn

1095-8584

pii

S0022282802920663

journal_volume

pub_type

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Metabolic plasticity and the promotion of cardiac protection in ischemia and ischemic preconditioning.