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.