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 x kg(-1) x day(-1)) and nifedipine (1 mg x kg(-1) x 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 ventricle, isradipine treatment prevented, in a significant manner, all the above spontaneous pathological changes, while nifedipine had no effect. Our present observations provide evidence for the first time that in vivo treatment with a DHP Ca2+ channel blocker, isradipine, is cardioprotective against the development of necrosis in hereditary cardiomyopathy in the hamster. It is possible that the protective effect of isradipine in CMH could be largely due to the indirect blockade of Ca2+ influx through the Na+-Ca2+ exchanger as well as to possible direct blockade of Ca2+ influx through the T-type Ca2+ channel.
Jacques
Danielle
D
Department of Anatomy and Cell Biology, Faculty of Medicine, University of Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.
Bkaily
Ghassan
G
Jasmin
Gaétan
G
D'Orléans-Juste
Pedro
P
Chahine
Mirna
M
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020747:Calcium Channels, T-Type / Q000187:drug effects; D002311:Cardiomyopathy, Dilated / Q000151:congenital / Q000517:prevention & control*; D006224:Cricetinae; D017275:Isradipine / Q000494:pharmacology* / Q000627:therapeutic use*; D009336:Necrosis; D009543:Nifedipine / Q000494:pharmacology*; D026941:Sodium Channel Blockers / Q000494:pharmacology
D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D026941:Sodium Channel Blockers; D009543:Nifedipine; D017275:Isradipine