EFFECTS OF SOME STEROID AND NONSTEROID LACTONES ON POTASSIUM EXCHANGE AND PHYSIOLOGICAL PROPERTIES OF THE ISOLATED PERFUSED GUINEA PIG VENTRICLE

¹ Department of Pharmacology, University of Cincinnati College of Medicine, Cincinnati 19, Ohio

The effects of 2 steroid and of 3 nonsteroid lactones on the hypodynamic isolated guinea pig ventricle preparation have been compared. Ouabain and dihydro-ouabain produced positive inotropic effects in all concentrations used. Petulin in sufficiently high concentrations caused a brief increase in contraction height followed by a return to the hypodynamic level. In lesser concentrations it did not alter contraction height. Alpha-angelicalactone and pulvinic acid dilactone in sufficiently high concentrations caused only negative inotropic effects. All of the lactones caused contracture, the extent of which varied with the concentration. In the case of the steroid lactones, contracture occurred only with concentrations higher than those necessary to restore contraction height to normal, while the nonsteroid lactones caused contracture in concentrations which did not alter the height of contraction.

All of the lactones caused the ventricles to lose potassium to the perfusate. Small concentrations of dihydro-ouabain or ouabain caused only an initial loss, after which the ventricles were in potassium balance. The initial loss was evident in higher concentrations, also, but the period of stabilization was brief and was followed by a more rapid loss parallel to the development of contracture. The nonsteroid lactones caused a more continuous loss of potassium even in the lower concentrations. The final extent of contracture achieved is directly related to the average rate at which potassium is lost rather than to the total magnitude of the loss. The importance of the rate of potassium loss is consistent with the concept of a small, rapidlyexchanging potassium compartment which loses potassium in response to the drugs but which is being continually renewed by a larger, more slowly-exchanging compartment. By this hypothesis, the ratio of the rates of depletion and of repletion of the small compartment would determine the rate of development and the extent of contracture.

Neither contracture nor inotropic effects was related to effects on the excitable membrane. Electrical activity of the heart continued even when the beat was stopped before contracture began, and it could continue during contracture. Higher concentrations of any of the lactones abolished electrical excitability. In 8 experiments the electrical aspects of fibrillation were recorded as contracture developed.