Hemodynamic changes and neurohumoral regulation during development of congestive heart failure in a model of epinephrine-induced cardiomyopathy in conscious rabbits

Abstract

Background: The present study was designed to study the progression of heart failure in rabbits with catecholamine-induced cardiomyopathy. Methods and Results: We investigated the effects of three repetitive applications (at 16-day intervals) of high-dose epinephrine (first infusion, 5 μg/kg/min for 60 minutes; second and third infusions, 4 μg/kg/min for 60 minutes) on hemodynamics, echocardiographic parameters, and plasma hormone levels in eight conscious rabbits chronically instrumented with a Doppler flow probe around the proximal abdominal aorta and a catheter in the right atrium. Mean arterial pressure and blood flow velocity, as well as the acceleration of blood flow velocity ( df dt ) in the proximal abdominal aorta were progressively reduced, and right atrial pressure was significantly elevated. On echocardiography, progressive left ventricular (LV) dilatation with depressed LV systolic function and an increase in LV mass were observed. Plasma atrial natriuretic peptide level was enhanced approximately fourfold after each epinephrine infusion, with a tendency to return to baseline values. Plasma renin activity (PRA) was increased after the first epinephrine application (3.0 ± 0.5 to 6.4 ± 0.9 ng angiotensin I (AI)/mL/h; P < .05), followed by a return to control levels. After the second epinephrine infusion, a significant decrease to 1.0 ± 0.3 ng AI/mL/h ( P < .05) was observed. After the third catecholamine treatment, PRA levels insignificantly increased. Plasma vasopressin level significantly increased from 0.5 ± 0.2 to 1.1 ± 0.5 pg/mL ( P < .05) after the second epinephrine infusion. Conclusion: Repetitive infusions of high doses of epinephrine induce a cardiomyopathy with progressive hemodynamic deterioration, LV dilatation and hypertrophy, depressed systolic function, and different stages of neurohumoral compensation. This model appears to be suitable to study the progression of chronic heart failure by serial measurements in a small animal preparation.