Pathophysiological and biochemical characterisation of an avian model of dilated cardiomyopathy: comparison to findings in human dilated cardiomyopathy
Objective: With the recent availability of human myocardium, many animal models have been shown to be unsuitable as models of human heart failure. The aim of this study was to describe the pathophysiological changes in a model of dilated cardiomyopathy in turkey poults and to compare them to results obtained from failing human hearts. Methods: After receiving furazolidone for 2-3 weeks, animals developed cardiomyopathy (Fz-DCM) and were studied at the whole heart and isolated muscle level. Myofibrillar ATPase activity and noradrenaline turnover were determined in tissue homogenates in failing and non-failing control hearts. Results: Fz-DCM animals had greater heart weights, heart weight/body weight ratios, and end diastolic volumes. Fractional shortening of the left ventricle and systolic blood pressures were reduced (p2+]o responsiveness was similar for Fz- DCM and normal animals, responsiveness to isoprenaline was significantly reduced in Fz-DCM hearts. Cardiomyopathic animals displayed diminished noradrenaline content in the left ventricle. Fractional noradrenaline turnover was higher (pConclusions: In this model of dilated cardiomyopathy: (1) relaxation is markedly prolonged; (2) the response to β adrenergic stimulation is diminished; (3) Mg-ATPase activities and myofibrillar protein content are reduced; and (4) sympathetic activity in the heart is markedly increased with depletion of noradrenaline stores. Furthermore, a reduction in tissue noradrenaline content per se is a misleading index of the dynamic state of cardiac noradrenaline stores. With its similarities to human cardiomyopathy, this model promises to provide new insights into the pathophysiology and progression of dilated cardiomyopathy. Cardiovascular Research 1993;27:2212-2221