Electrophysiologic correlates of the inotropic effects of Isoproterenol in canine myocardium

Abstract The action of l -isoproterenol was studied in isolated canine papillary muscles. The simultaneous action potential and contraction traces were first recorded in digital form on magnetic tape and later measured and analyzed by a computer program. The data were controlled and grouped to permit a three-way analysis of variance in order to test significant effects and correlations. Complete dose-response curves were performed both before and after beta-adrenergic blockade with (±)propranolol. It was demonstrated that isoproterenol produced and increase in the peak potential, the height and duration of the plateau (phase 3), and the rate of repolarization of the action potential (phase 4). Corresponding increases in peak tension, time to peak tension, rate of tension development, and rate of relaxation of the contraction were noted. At the highest isoproterenol concentrations, occasional after-potentials and after-contractions occurred. The changes in the action potential were explained by changes in the inward calcium current, while the inotropic effect on the contraction was attributed to the resulting increase in intracellular calcium concentration. These effects were all blocked by the addition of propranolol, but the blockade could be overcome by increasing the isoproterenol concentration of the perfusate.