Effects of verapamil on experimental cardiomyopathy in the Bio 14.6 Syrian hamster

Abstract

The Bio 14.6 Syrian hamster provides a good model for experimental study of cardiomyopathy. Cardiac receptor binding sites (alpha-1-, beta- and calcium antagonists) were studied in early (21 days old) and late (70 days old) stages of cardiomyopathy. The effects of verapamil on histologic features and free radicals in the heart were studied. The number of alpha-1- and beta-cardiac receptor binding sites was significantly greater in the late stage of cardiomyopathy when compared with findings in normal golden hamsters used as controls. The calcium antagonist receptors were significantly increased in the early stage but alpha-1- and beta-receptors were not. Verapamil-treated hamsters received intraperitoneal injections of verapamil at a dose of 5 mg/kg per day for 70 days from age 20 days. The percent areas of fibrosis and calcification in the verapamil-treated group were significantly smaller than those in the control group. The concentrations of lipid peroxides in the whole heart and free radicals in the heart mitochondria were significantly higher in the cardiomyopathic hamsters, and verapamil inhibited the increase in free radical concentration in the hearts of these hamsters. This study confirms that the number of calcium channels is increased early in the course of cardiomyopathy in the Bio 14.6 Syrian hamster. A larger number of free radicals may participate in the accumulation of calcium and cell injury in the myocytes of these hamsters. Verapamil protects against myocardial damage and may do so by inhibiting voltage-dependent calcium uptake and by preventing cell injury from free radicals.

Prevention of cardiomyopathy in mouse models lacking the smooth muscle sarcoglycan-sarcospan complex

“…Various early studies have shown beneficial effects of verapamil in the cardiomyopathic hamster that carries a deletion within the δ-sarcoglycan gene (17,18). Here we also demonstrate beneficial effects of verapamil on the cardiomyopathic phenotype in a more genetically defined mouse model deficient for δ-sarcoglycan.…”

“…The beneficial use of verapamil has been shown extensively in a variety of diseases such as hypertension and cardiac arrhythmias, as well as in humans and animal models with cardiomyopathy (17,18,22,23). Interestingly, the cardioprotective efficacy of verapamil was attributed to increased transmural blood flow related to vasodilation of the coronary artery bed (17,22) as well as to the potential of verapamil to inhibit membrane calcium influx into cardiomyocytes (18). The current data reveal new compelling evidence that perturbed vascular function and intermittent ischemiclike events play a significant role in the pathogenesis of cardiomyopathy in Sgcb-and Sgcd-null mice.…”

Myocardial electrical propagation in patients with idiopathic dilated cardiomyopathy.

“…A relation between fibrous tissue and arrhythmias also may have therapeutic implications. Treatment with angiotensin-converting enzyme inhibitors and calcium antagonists has been shown to limit the development offibrosis in animal models ofcardiomyopathy (9,(75)(76)(77). Therefore, inhibition of collagen infiltration with failure to develop nonuniform propagation might be one mechanism by which these agents reduce mortality in animals with cardiomyopathy (9,78) and humans with congestive heart failure (79,80).…”

Expression of dihydropyridine receptor (Ca2+ channel) and calsequestrin genes in the myocardium of patients with end-stage heart failure.

“…Several studies have examined changes in the density ofthe Ca2+ antagonist receptor of the a, subunit of the dihydropyridine (DHP)-sensitive Ca2+ channel (Ca2+ channel) in the myocardium from cardiomyopathic hamsters (21)(22)(23)(24), rats with pressure overload (25,26) or infarction (27) and patients with idiopathic dilated cardiomyopathy (28,29) and hypertrophic cardiomyopathy (30). In these diverse animal models and human diseases there have been conflicting findings on the abundance of DHP binding sites (reviewed in reference 3 1 ).…”