Isradipine prevents the development of spontaneously occurring cardiac necrosis in cardiomyopathic hamster

Recent studies on the heart necrotizing process at the early stages of hamster polymyopathy have led us to believe that this hereditary disease derives from an anomalous transmembrane ion flux due to the presence of slow Na+ channels that contribute to intracellular Na+ accumulation which promote intracellular Ca2+ overload via the Ca2+ influx through the Na+–Ca2+ exchanger. In the present study, we investigated the potential beneficial effect of chronic treatment with a dual L-type Ca2+ and slow Na+ channel blockers isradipine, on the development of necrosis in myopathic hamster hearts. Young cardiomyopathic (CM) hamsters (CMH) were treated with isradipine (0.1 mg·kg–1·day–1) and nifedipine (1 mg·kg–1·day–1) for 4 consecutive weeks. Microscopic assessments were carried out in staged serial paraffin sections of heart ventricles from tissues freshly dissected at autopsy. In comparison with control nontreated hearts, which exhibited numerous necrotic calcific foci, myolytic lesions, and dilated right ventri...