The role of calcium in ischemic myocardial injury.
Hypoxia and ischemia produce depression of myocardial contractile function and alterations in calcium homeostasis. Although both functional abnormalities and alterations in calcium handling are reversible under some conditions, reoxygenation or reperfusion can also lead to paradoxical augmentation of injury. Under many conditions of ischemia and reperfusion, however, a causal relation between altered calcium handling and cellular injury has been difficult to establish. Calcium entry through specific calcium channels during and after hypoxic insult can account for only a fraction of the observed pathologic transsarcolemmal calcium flux; sodium-calcium exchange also appears to contribute to calcium influx but to a limited degree. During reoxygenation calcium also appears to enter through nonspecific sarcolemmal permeability changes. The hypothesis that mitochondria are calcium loaded by hypoxia and reoxygenation and that the calcium loading produces mitochondrial dysfunction has not been substantiated convincingly. Brief hypoxia can produce mitochondrial dysfunction without mitochondrial calcium overload, whereas calcium overload per se does not initially produce irreversible cellular injury. Under conditions of prolonged ischemic insult, with or without reperfusion, it is likely that disturbed calcium homeostasis does play a role in ultimate cellular injury. However, available data fall short of establishing intracellular calcium overload as a necessary or sufficient condition to produce irreversible myocardial cell injury.
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D003327:Coronary Disease / Q000209:etiology* / Q000503:physiopathology; D006019:Glycolysis; D006706:Homeostasis; D000860:Hypoxia / Q000503:physiopathology; D008929:Mitochondria, Heart / Q000378:metabolism; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism; D010085:Oxidative Phosphorylation; D010101:Oxygen Consumption; D012964:Sodium / Q000378:metabolism
D012964:Sodium; D002118:Calcium