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Effects of verapamil on experimental cardiomyopathy in the Bio 14.6 Syrian hamster
A Kobayashi1, T Yamashita, M Kaneko
1Third Department of Internal Medicine, Hamamatsu University School of Medicine, Shizuoka Prefecture, Japan.
Insights
This study shows increased calcium channels early in cardiomyopathy in Syrian hamsters. Verapamil treatment reduced fibrosis and calcification, suggesting it protects against heart damage by managing calcium and free radicals.
Area of Science:
- Cardiology
- Pharmacology
- Biochemistry
Background:
- The Bio 14.6 Syrian hamster is a suitable model for studying cardiomyopathy.
- Cardiac receptor binding sites, including alpha-1, beta, and calcium antagonists, were investigated in early and late stages of the disease.
Purpose of the Study:
- To investigate cardiac receptor binding sites in early and late stages of cardiomyopathy.
- To evaluate the effects of verapamil on histologic features and free radicals in the heart.
- To explore the role of free radicals in calcium accumulation and myocyte injury.
Main Methods:
- Studied alpha-1, beta, and calcium antagonist receptor binding sites in early (21 days) and late (70 days) cardiomyopathy stages.
- Administered verapamil (5 mg/kg/day for 70 days) to hamsters from age 20 days.
- Assessed fibrosis, calcification, lipid peroxides, and mitochondrial free radicals.
Main Results:
- Alpha-1 and beta-receptor sites were higher in late-stage cardiomyopathy.
- Calcium antagonist receptors increased in early stages; alpha-1 and beta-receptors did not.
- Verapamil treatment significantly reduced fibrosis and calcification.
- Cardiomyopathic hamsters showed higher lipid peroxides and mitochondrial free radicals; verapamil inhibited this increase.
Conclusions:
- Calcium channel numbers increase early in Bio 14.6 Syrian hamster cardiomyopathy.
- Free radicals may contribute to calcium accumulation and myocyte injury.
- Verapamil offers protection against myocardial damage, potentially by inhibiting calcium uptake and preventing free radical-induced injury.
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.