Abstract
Brief periods of ischemia and reperfusion are able to protect the heart from irreversible injury induced by consequent prolonged ischemia and reperfusion stress. This phenomenon called ischemic preconditioning (IP) may limit infarct size, enhance postischemic recovery of cardiac function, reduce reperfusion arrhythmias and vascular dysfunction. Mechanisms of IP are tightly related to alterations of efficiency of metabolic pathways and maintenance of ion homeostasis in ischemic cardiac myocytes. They may be initiated by formation of various triggers (adenosine, bradykinin, NO, free oxygen radicals etc.) that interact with receptors of cardiomyocytes and vascular endothelium or directly alter activity of enzymes. These interactions lead to activation of different pathways of intracellular signal conduction involving contribution of mediators and complex of the secondary messengers of IP. The most typical of them are e-isoform of protein kinase C and the ATP-dependent potassium channels. Biochemical pathways of molecular signaling in the preconditioned myocardium may be different, but always have same final effectors -- intracellular metabolism and ion homeostasis. As a rule, successfully preconditioned myocardium exhibits improved energy state of ischemic cardiomyocytes, reduced Ca(+) overload and attenuated damage of the sarcolemma and mitochondrial membranes. These beneficial changes provide myocardial salvage under conditions of deficient supply of cardiomyocytes with energy substrates and oxygen. Stimulation of adaptative mechanisms of IP is possible with specific receptor agonists or activation of secondary messenger pathways without causing ischemia. At present study of such pharmacological approaches to treating ischemia is a high priority task. In clinical practice selective openers of ATP-dependent potassium channels, A(1) and A(2) adenosine receptor agonists and Na(+)/H(+) exchange inhibitors are used to affect the final effectors of signaling pathways. These pharmacological agents are explored in transluminal coronary angioplasty, cardiac surgery and organ transplantation.
