The influence of oligomycin on the actions of epinephrine and theophylline upon the perfused rat heart

Abstract

Rat hearts were perfused with media containing pyruvate and iodoacetate with and without oligomycin. In the absence of oligomycin, both heart rate and force of contraction were well maintained. When oligomycin was included in the perfusion medium, there was a negative inotropic effect, a marked atrioventricular (A-V) block and a slowly developing contracture. In the oligomycin-treated heart, epinephrine or theophylline increased pacemaker activity, reduced the extent of A-V blockade and greatly accelerated the development of contracture. Rapid occurrence of contracture also followed electrical stimulation. Epinephrine was capable of exerting a positive inotropic effect in electrically driven hearts perfused with iodoacetate, pyruvate and oligomycin. Measurements of adenine nucleotides and creatine-phosphate showed that at the time when heart rate was markedly depressed by oligomycin ATP concentrations were not greatly reduced, although creatine-phosphate levels had decreased by 40 per cent. Administration of epinephrine or theophylline to these hearts greatly diminished the levels of high-energy phosphate. It was concluded that formation of new ATP from glycolysis or the respiratory chain is not required for the initial inotropic action of epinephrine or theophylline. The data allow one to speculate that the primary effects of these compounds or of 3′,5′ cyclic AMP may be concerned with calcium movements in the myocardial cell.