Pathogenetic Role for Calcium in Stunning?
Cellular calcium homeostasis is disturbed during brief periods of ischemia, with free cytosolic Ca ([Ca2+]i) rising severalfold within 10–15 minutes (or even sooner). Nevertheless, the myocardial cells’ ability to regulate Ca recovers quickly after reperfusion, unlike the lingering depression of contractile function known as stunning. This brief commentary considers the hypothesis that the rise in cell calcium during ischemia and during early reperfusion leaves behind stunning as an unwelcome legacy. This idea by no means excludes the involvement of other factors, such as free radicals; instead, it suggests a possible common pathway for cell injury by a variety of specific agents. A provocative feature of the formulation is the idea that the crucial lesion in stunning occurs at the level of the contractile proteins, rather than more proximally.
KeywordsMyocardial Cell Contractile Protein Calcium Overload Myocardial Stunning Cell Calcium
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- 9.Lee H-C, Smith N, Mohabir R, Clusin WT. Cytosolic calcium transients from the beating mammalian heart. Proc Natl Acad Sci USA 1987; 252: C441 — C449.Google Scholar
- 12.Kusuoka H, Porterfield JK, Weisman HF, Weisfeldt ML, Marban E. Pathophysiology and pathogenesis of stunned myocardium: Depressed Ca2+ activation of contraction as a consequence of reperfusion-induced cellular calcium overload in ferret hearts. J Clin Invest 1987; 79: 950–961.PubMedCrossRefGoogle Scholar
- 17.Olney J, Collins RC, Sloviter RS. Excitotoxic mechanisms of epileptic brain damage. In: Delgado-Escueta AV, Ward AA Jr., Woodbury DM, Porter RJ, eds. Advances in Neurology, Vol 44. New York, Raven Press, 1986: 857–877.Google Scholar
- 21.Corretti MC, Koretsune Y, Chacko VP, Zweier JL, Marban E. Glycolytic inhibition and calcium overload as consequences of exogenously-generated free radicals in rabbit hearts. J Clin Invest 1991, in press.Google Scholar