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American Journal of Pathology, Vol 131, 137-145, Copyright © 1988 by American Society for Investigative Pathology
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JS Elz and WG Nayler
Department of Medicine, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia.
Reperfusing hearts after an ischemic episode can result in cellular Ca2+ overload. This is accompanied by the formation of contraction bands, loss of sarcolemmal integrity, and mitochondrial disruption. The present study investigated the effect of uncoupling oxidative phosphorylation with 2,4-dinitrophenol (DNP) during reperfusion after 30 or 60 minutes of ischemia on this reperfusion-induced Ca2+ gain. After 60 minutes' ischemia, reperfusion with 1 mM DNP delayed the accumulation of Ca2+ and increased the duration of reperfusion before sarcolemmal disruptions were evident. This suggested that once sarcolemmal integrity is lost, Ca2+ will freely enter the cells irrespective of whether the mitochondria are able to accumulate Ca2+. After 30 minutes ischemia, reperfusion for up to 30 minutes with 0.1 or 1 mM DNP attenuated the Ca2+ gain and maintained sarcolemmal integrity. Because the authors previously found that maintaining sarcolemmal integrity alone does not totally abolish Ca2+ gain, it is suggested that DNP must prevent the entry of Ca2+ that occurs via route(s) other than those created by the loss of sarcolemmal integrity.
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