The information presented enables us to begin to classify the various forms of cardiac dysfunction within a rational framework that individually considers each step in excitation-contraction coupling. Table 2 summarizes our observations with regard to hypoxic,21,22 stunned,27,37 and hibernating42 myocardium. The crucial deficit in hypoxia involves a decrease in myofilament responsiveness to Ca2+ that is straightforwardly attributable to changes in Pi (and, to a lesser extent, pHi). The lesion of excitation-contraction coupling in stunning also occurs at the level of myofilament Ca2+ responsiveness, but here neither Pi nor pHi can be implicated because each quickly returns to normal upon reperfusion. Finally, the availability of activator Ca2+ appears to be the limiting factor in hibernation. The findings are of immediate interest in producing a better understanding of the pathophysiology of cardiac contractile disorders, but the long-term pay-off promises to be even greater: clear identification of the site of injury in any given condition will help focus the often haphazard biochemical approaches that have been brought to bear on these problems. For example, the finding that Ca2+ transients are not decreased in stunned myocardium sheds doubt on the relevance of explanations that focus on impairments in the pathways that control activator Ca2+.1 Instead, attention can now be more profitably directed to determining the nature and origin of the decrease in myofilament Ca2+ responsiveness. Quite a different path will have to be followed to elucidate hibernation. The demonstration that perfusion pressure modulates the amplitude of Ca2+ transients should further motivate the ongoing search for specific mediators of excitation-contraction coupling elaborated by endothelial cells, smooth muscle cells, or myocardial cells in response to changes in coronary perfusion.54.
|Original language||English (US)|
|Number of pages||8|
|State||Published - Feb 1991|
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine