Pathophysiological and biochemical characterisation of an avian model of dilated cardiomyopathy: Comparison to findings in human dilated cardiomyopathy

Roger J. Hajjar*, Ronglih Liao, James B Young, Farid Fuleihan, Mark G. Glass, Judith K. Gwathmey

*Corresponding author for this work

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

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 (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 frequency of stimulation was positive in control muscles up to 1.7 Hz, whereas in Fz-DCM muscles the relationship was sharply negative above 1 Hz. Time to 80% relaxation was markedly slower in the Fz-DCM muscles. Although [Ca2+]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 (p<0.05) in the cardiomyopathic birds. In skinned fibre preparations from control and Fz-DCM hearts calcium activations were similar. Maximum 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) 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.

Original languageEnglish (US)
Pages (from-to)2212-2221
Number of pages10
JournalCardiovascular Research
Volume27
Issue number12
DOIs
StatePublished - Jan 1 1993

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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