Abnormalities in sympathoneuronal regulation are localized to failing myocardium in rabbit heart

Department of Medicine, Keio University School of Medicine, Tokyo, Japan.

OBJECTIVES. This study investigated the differences in sympathoneuronal regulation between acute left ventricular failure and chronic biventricular failure to determine whether an increase in plasma norepinephrine concentration plays a primary role in the genesis of the desensitization phenomenon in heart failure. BACKGROUND. It remains to be determined whether plasma norepinephrine plays a primary role in the pathogenesis of sympathetic desensitization in heart failure in vivo. METHODS. Acute left ventricular failure was induced by aortic regurgitation in seven rabbits. Chronic heart failure was induced by adriamycin treatment in another seven rabbits. RESULTS. Cardiac output was lower in rabbits with aortic regurgitation than in seven sham-operated rabbits. Left ventricular end-diastolic pressure was higher in rabbits with aortic regurgitation, but no significant difference in right ventricular end-diastolic pressure was observed. Beta-adrenoceptor density and norepinephrine concentration in the left ventricular myocardium were lower in rabbits with aortic regurgitation; no such differences were observed for the right ventricular myocardium. Cardiac output was lower in adriamycin-treated rabbits than in seven control rabbits. Both left and right ventricular end-diastolic pressures were higher in experimental rabbits than in control rabbits. Myocardial beta-adrenoceptor density and norepinephrine content were reduced in both ventricles. CONCLUSIONS. In chronic heart failure induced by adriamycin, sympathoneuronal activity was altered in both ventricles, whereas in acute left ventricular failure induced by aortic regurgitation, sympathoneuronal activity was affected only in the left ventricle despite a similar increase in plasma norepinephrine concentration in both animal models. Local abnormalities in sympathoneuronal regulation in failing myocardium therefore appear to be responsible for these phenomena.

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