In three experimental series, acute hemodynamic overload of the left ventricle, focal ischemia of the left ventricle, and diphtheritic intoxication were modeled in rabbits. On days 1, 3, and 5 of the experiments, activity of myocardial caspase-3 and caspase-8 were measured separately in the left and right ventricles. In the left ventricle, caspase-3 activity increased in all 3 modeled pathological processes, while in the right ventricle this parameter increased during acute overload and ischemic injury to the left ventricle. Caspase-8 activity increased only in the left ventricle during its hemodynamic overload and remained unchanged in other cases. It was concluded that induction of the caspase cascade can be considered as a nonspecific response to myocardial damage. In this case, specific mechanisms responsible for generation and transmission of apoptotic stimuli in cardiomyocytes have unique features. © 2011 Springer Science+Business Media, Inc.