Preconditioning myocardium with ischemia.
Preconditioning and stunning are the chief adaptive changes induced in myocardium by a brief episode of reversible ischemia followed by arterial reperfusion. In the dog heart, both coexist for a period of at least 20 minutes of reperfusion, but after 120 minutes of reflow, preconditioning is much diminished, while stunning remains fully developed. Preconditioned, stunned, myocardium differs from control "virgin" myocardium in that adenine nucleotide content is reduced to about 50-70% of control, whereas creatine phosphate (CP) greatly exceeds normal--the so-called CP overshoot. When preconditioned myocardium is subjected to sustained ischemia, ATP utilization and anaerobic glycolysis occur at much slower rates than those observed in virgin myocardium. As a result of the early difference in metabolic rate, a longer period of ischemia is required for the ATP and lactate of the preconditioned tissue to reach the levels associated with irreversible injury. Associated with this change is a delay in myocyte death. The molecular events responsible for slower ischemic metabolism and associated tolerance of preconditioned, stunned tissue to a new ischemic episode are not known. Among the reactions that could cause a reduction in energy metabolism is reduced approximately P expenditure by stunned myocardium attempting to contract during the initial phase of ischemia. However, results from in vivo and in vitro experiments suggest that although stunning may be necessary for preconditioning to develop, it alone is not sufficient to cause preconditioning. Alternatively, metabolic changes may be explained by depressed activity of the mitochondrial ATPase during the episode of sustained ischemia. However, no direct experimental evidence supporting this hypothesis is available up to the present time.
Jennings
R B
RB
Department of Pathology, Duke University Medical Center, Durham, NC 27710.
Murry
C E
CE
Reimer
K A
KA
D000255:Adenosine Triphosphate / Q000096:biosynthesis / Q000378:metabolism; D000818:Animals; D003327:Coronary Disease / Q000209:etiology* / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D015425:Myocardial Reperfusion
D006360:Heat-Shock Proteins; D000255:Adenosine Triphosphate