Protection against cellular damage in the rat heart by iodoacetate.
In this comparative study, rat hearts were perfused at 37 degrees C with three clearly defined protocols: the Ca2+ paradox, the O2 paradox, and with 20 mM caffeine. Each protocol involved an initial priming (Ca2+o depletion or anoxia; stage 1) and subsequent full activation (Ca2+o repletion, caffeine or reoxygenation; stage 2) of the damage system of the sarcolemma. Iodoacetate (1 mM) provided complete protection in the O2 paradox and over 80% protection in the Ca2+ paradox and caffeine protocols against creatine kinase release when present throughout the experiment (P < 0.001). Almost identical protection was found when iodoacetate was present only in stage 2 (P < 0.001). However, it was concluded that iodoacetate had limited protective effects when present only in stage 1 in any of the three protocols and that its action is to inhibit the activity of the transsarcolemma damage system in stage 2 when it has been activated in stage 1. It is suggested that iodoacetate interacts with thiol groups on the damage system of the sarcolemma.
Harding
R J
RJ
School of Biological Sciences, Derby Building, University of Liverpool, L69 3GS, United Kingdom.
Duncan
C J
CJ
D000818:Animals; D002110:Caffeine / Q000378:metabolism; D002118:Calcium / Q000172:deficiency / Q000378:metabolism; D003402:Creatine Kinase / Q000378:metabolism / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D007461:Iodoacetates / Q000494:pharmacology*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010100:Oxygen / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D007461:Iodoacetates; D002110:Caffeine; D003402:Creatine Kinase; D010100:Oxygen; D002118:Calcium