Effects of 2,3-butanedione monoxime (BDM) on contracture and injury of isolated rat myocytes following metabolic inhibition and ischemia.
The relationship between myocardial cell contracture and injury during total metabolic inhibition (amylobarbital and iodoacetic acid) and ischemia was examined, using 5-50 mM butanedione monoxime (BDM) as an inhibitor of contracture. BDM had no apparent effect on control myocytes during 180 min incubations, but inhibited contracture following anoxia or ischemia in a dose-dependent fashion, as directly quantitated by length/width ratios. Cellular ATP levels decreased at a similar rate in the absence or presence of BDM, following metabolic inhibition. BDM-mediated inhibition of contracture was associated with accelerated cell injury, as defined by: the uptake of an extracellular marker (trypan blue) by the cardiomyocytes, by direct analysis of myoglobin released into the supernatant and by ultrastructural demonstration of defects in sarcolemmal membrane integrity. Calcium was not required for BDM's enhancement of injury, in that cells incubated in calcium free-EGTA buffer showed a similar BDM-mediated acceleration of injury. In the presence or absence of calcium, enhancement of injury was more marked in cells osmotically stressed with a brief incubation in hypotonic buffer, than in cells resuspended in isotonic media. It is concluded that BDM enhances development of osmotic fragility of inhibited or ischemic cardiomyocytes and that contracture is not a necessary contributing factor to myocardial cell death.
Armstrong
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SC
Department of Pathology, East Tennessee State University, James H. Quillen College of Medicine, Johnson City 37614.
Ganote
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CE
D000255:Adenosine Triphosphate / Q000378:metabolism; D000654:Amobarbital / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015687:Cell Hypoxia / Q000502:physiology*; D003931:Diacetyl / Q000031:analogs & derivatives* / Q000494:pharmacology; D007461:Iodoacetates / Q000494:pharmacology; D009200:Myocardial Contraction / Q000502:physiology*; D009996:Osmotic Fragility / Q000187:drug effects; D051381:Rats; D012518:Sarcomeres / Q000187:drug effects / Q000648:ultrastructure
D007461:Iodoacetates; C004717:diacetylmonoxime; D000255:Adenosine Triphosphate; D000654:Amobarbital; D003931:Diacetyl; D002118:Calcium