PATHOPHYSIOLOGICAL AND BIOCHEMICAL-CHARACTERIZATION OF AN AVIAN MODELOF DILATED CARDIOMYOPATHY - COMPARISON TO FINDINGS IN HUMAN DILATED CARDIOMYOPATHY

Objective: With the recent availability of human myocardium, many anim al models have been shown to be unsuitable as models of human heart fa ilure. The aim of this study was to describe the pathophysiological ch anges in a model of dilated cardiomyopathy in turkey poults and to com pare them to results obtained from failing human hearts. Methods: Afte r receiving furazolidone for 2-3 weeks, animals developed cardiomyopat hy (Fz-DCM) and were studied at the whole heart and isolated muscle le vel. Myofibrillar ATPase activity and noradrenaline turnover were dete rmined 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 th e left ventricle and systolic blood pressures were reduced (p<0.01) in myopathic animals. Isolated perfused hearts had lower peak developed pressures (p<0.01). Isolated muscle preparations showed no significant differences in peak twitch forces between control and Fz-DCM muscles at a 1 Hz stimulation rate. The relationship between force and frequen cy of stimulation was positive in control muscles up to 1.7 Hz, wherea s in Fz-DCM muscles the relationship was sharply negative above 1 Hz. Time to 80% relaxation was markedly slower in the Fz-DCM muscles. Alth ough [Ca2+](0) responsiveness was similar for Fz-DCM and normal animal s, responsiveness to isoprenaline was significantly reduced in Fz-DCM hearts. Cardiomyopathic animals displayed diminished noradrenaline con tent in the left ventricle. Fractional noradrenaline turnover was high er (p<0.05) in the cardiomyopathic birds. In skinned fibre preparation s from control and Fz-DCM hearts calcium activations were similar. Max imum myofibrillar ATPase activities were, however, significantly lower in myopathic animals and myofibrillar protein content was reduced by 25%. Conclusions: In this model of dilated cardiomyopathy: (1) relaxat ion is markedly prolonged; (2) the response to beta adrenergic stimula tion is diminished; (3) Mg-ATPase activities and myofibrillar protein content are reduced; and (4) sympathetic activity in the heart is mark edly 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 simila rities to human cardiomyopathy, this model promises to provide new ins ights into the pathophysiology and progression of dilated cardiomyopat hy.