Abstract
It has been suggested that myocardial apoptosis occurs in cardiac remodeling after myocardial infarction (MI). The apoptosis possibly plays an important role in the process of cardiac remodeling, especially in the formation of ventricular size. In this study, we have tried to clarify the pathophysiological link between apoptosis in left ventricular remodeling and cardiac functions by modulating the signal transduction pathways for apoptotic death of cardiomyocytes. A rat model of MI was made by the coronary artery ligation. Either a caspase-3 inhibitor II or a calpain inhibitor XII was administrated immediately after the ligation. Blood pressure in the tail, blood flow velocity in the carotid artery and heart rate were measured for estimating the changes in cardiac functions. No significant difference was observed in blood flow velocity among the experimental protocol. In contrast, both the blood pressure and heart rate were different significantly between animals treated without and with an inhibitor of either caspase-3 or calpain for several days after 4 days after the ligation, and these parameters in animals with inhibitors of apoptosis were almost the same as those in sham-operated ones. These findings suggest a possibility that the inhibition of activation of either caspase-3 or calpain activation during the early phase of left ventricular remodeling ameliorates the cardiac function in the remodeled hearts. [Jpn J Physiol 55 Suppl:S235 (2005)]
