The effect of dobutamine on myocardial performance and high-energy phosphate metabolism at different stages of heart failure in cardiomyopathic hamsters: A 31P MRS study

Abstract

Dobutamine has been shown to exert disparate clinical effects in patients with cardiomyopathy and heart failure. This study evaluated the effects of dobutamine on hemodynamics and energetics in isolated, perfused myopathic hamster hearts at a moderate and advanced stage of heart failure. Biochemical changes were correlated with left ventricular developed pressure, coronary flow, and myocardial oxygen consumption. During dobutamine treatment left ventricular developed pressure increased in the control and moderate heart failure group 28.0 ± 1.0% and 114.2 ± 11.6%, respectively. Myocardial oxygen consumption increased 50.1 ± 9.1% and 45.5 ± 16.0%, respectively. There were no significant changes of left ventricular developed pressure and myocardial oxygen consumption in the advanced heart failure group. Inorganic phosphate (P i) increased in the control group from 6.8 ± 0.5 to 11.4 ± 1.2 mmol ( p < 0.005) and in the advanced heart failure group from 10.4 ± 1.1 to 15.3 ± 1.2 mmol ( p < 0.01). Phosphocreatine (PCr) and β-ATP (adenosine triphosphate) decreased in the control group from 12.2 ± 0.4 to 8.7 ± 0.7 mmol ( p < 0.001) and 10.4 ± 0.8 to 7.7 ± 0.7 mmol ( p < 0.02), respectively. PCr P i ratio, reflecting mitochondrial function, fell in the control and advanced heart failure group from 1.84 ± 0.14 to 0.84 ± 0.14 ( p < 0.02) and 0.81 ± 0.16 to 0.37 ± 0.08 ( p < 0.03), respectively. Thus in cardiomyopathic hamsters dobutamine improved mechanical performance and thermodynamic efficiency in moderate stages of heart failure by improving mitochondrial activity, but did not improve mechanical performance in an advanced stage of heart failure. These experiments provide insight into the disparate clinical effects of dobutamine at various stages of heart failure.