Vol. 284, Issue 1, 125-135, 1998

Characterization of Stress-Induced Sudden Death in Cardiomyopathic Hamsters

Nobuya Matsuoka, Hiroyuki Arakawa, Hiroshi Kodama and Isamu Yamaguchi

Basic Research Group, Tsukuba Research Laboratories, Fujisawa Pharmaceutical Co. Ltd., Tsukuba, Ibaraki, 300-26 Japan

Stress is known clinically and experimentally to contribute to the development or exacerbation of cardiovascular dysfunction. In an attempt to construct an animal model of stress-induced cardiovascular dysfunction and to understand its mechanisms, the effects of cold-immobilization stress and its cardiovascular consequences were investigated in cardiomyopathic Syrian hamsters (BIO 14.6) and age-matched healthy control hamsters. Repeated exposure (5 days) to cold-immobilization in the supine position induced no detectable ill effects in the healthy control hamsters but had a lethal effect in the cardiomyopathic hamsters: more than half of the animals died suddenly during or after the stress sessions. Autopsy study of these animals showed significant increases in the weights of the heart, adrenal, liver and kidney and in the serum levels of alkaline phosphatase, urea nitrogen, creatinine and glucose in the cardiomyopathic hamsters subjected to the stress. Propranolol (0.1-10 mg/kg i.p.) administered just before each cold-immobilization for 5 consecutive days dose-dependently and significantly prevented the lethal effects of the stress. Furthermore, it was demonstrated that the drug significantly reduced the increase in the weights of the heart, adrenal, liver and kidney observed in the stressed cardiomyopathic hamsters, whereas phentolamine (0.1-10 mg/kg) and atropine (0.1-10 mg/kg) did not prevent the stress-induced sudden death. The series of acute experiments using single exposure of this stress revealed that the stress evoked severe arrhythmia in some of the cardiomyopathic hamsters and increased the levels of circulating catecholamines in both healthy and cardiomyopathic hamsters. These results taken together suggest that stress accelerates the cardiovascular dysfunction in cardiomyopathic hamsters and provide the first evidence that excitation of the sympathetic nerves, in which -adrenoceptors appear to be involved, but not the parasympathetic nerves, has an important role in the etiology of stress-induced cardiac sudden death of cardiomyopathic hamsters.