Distinct modulation of myocardial performance, energy metabolism, and [Ca2+]i transients by positive inotropic drugs in normal and severely failing hamster hearts

Abstract

The present study compared the effects of amrinone, dobutamine, dibutyryl cAMP, digoxin, and isoproterenol on mechanical performance, the high energy phosphate metabolites, and the [Ca2+]i transients in normal and cardiomyopathic hamster hearts with severe heart failure. In normal hearts dobutamine, dibutyryl cAMP, and isoproterenol increased left ventricular developed pressure, while amrinone and digoxin did not. However, the amplitude of [Ca2+]i transients was augmented with all drugs. Diastolic [Ca2+]i level was increased with dobutamine and lowered with dibutyryl cAMP and isoproterenol. In cardiomyopathic hearts with severe heart failure, left ventricular developed pressure, the amplitude of [Ca2+]i transients, the phosphorylation potential, and [cAMP]i were significantly depressed and left ventricular end-diastolic pressure and diastolic [Ca2+]i were significantly elevated when compared with normal hearts. Amrinone, dibutyryl cAMP, and isoproterenol improved mechanical performance while increasing [cAMP]i and the amplitude of [Ca2+]i transients, and decreasing diastolic [Ca2+]i. On the other hand, with dobutamine and digoxin diastolic [Ca2+]i was further increased and mechanical performance deteriorated with digoxin. Thus, distinct differences exist in modulation of mechanical performance, high-energy phosphate metabolism, and [Ca2+]i transients by positive inotropic drugs between normal and cardiomyopathic hearts with severe heart failure.