The effects of isoproterenol on the isolated perfused rat heart

In isolated hearts infused with up to 100 ug/ml isoproterenol (ISO), there was only a transient effect on the frequency of contraction, and no effect on buffer flow through the heart. Infusion of hearts with 40-60 or 70-100 ug/ml ISO produced an increase in the release of lactate dehydrogenase, but not creatine kinase. Microscopic examination of hearts revealed myocyte separation and cytoplasmic vacuolation, of similar severity, in both control and ISO infused hearts; there was no necrosis. The data from this experiment are consistent with the view that ISO has little or no direct toxic effect on the heart. Since ISO is cardiotoxic In vivo, it is reasonable to suppose that this toxicity is linked primarily to the pharmacological effects of the drug. However, our study does not exclude the possibility that under the stressed conditions prevailing in vivo following a challenge with ISO, the susceptibility of myocytes to a direct toxic effect of ISO may increase.