Effects of Dibutyryl Cyclic AMP on contractile Performance of Isolated Heart Muscle Depressed by Thiamylal and Halothane

Abstract

Effects of dibutyryl cyclic AMP (D-cAMP) on contractile performance of isolated dog heart muscle were investigated with special reference to its effectiveness for the reversal of myocardial depression produced by sodium thiamylal and halothane. D-cAMP increased the velocity of shortening at 0.4 g preload (V'max) and isometric force dose-dependently at concentrations over 1×10^-3 M and net-shortening over 2×10^-3M. However, the time course of its action was slow, with the peak effect about 70 min after the administration of the drug. This was a sharp contrast to a very rapid onset of action of epinephrine. When V'max was depressed to about 75% of the control by 3.3 mg% of thiamylal or 7.1 mg% of halothane, 3×10^-3M of D-cAMP counteracted the depression produced by thiamylal and V'max was increased to 160% of the control, but it failed to reverse the depression produced by halothane and V'max remained 90% of the control. When the concentrations of halothane were lower than 5 mg%, however, D-cAMP at this concentration increased V'max more than the control level. The different responses to D-cAMP of the myocardium depressed by thiamylal and halothane suggest that there may be some differences between these two anesthetic agents in the mechanism for depressing myocardial contractility.