The Effects of total and partial inhibition of the sodium and pottassium-activated Adenosine Triphosphatase on the isolated perfused rabbit heart

The effects of sodium pump blockade on myocardial potassium (K),so'dium (Na), calcium (Ca) , adenosine 5'- triphosphate (ATP),and creatine phosphate (CP) were studied in the isolated Langendorff-perfused rabbit heart.Changes in these parameters- were investigated in relation to the development of ventricular fibrillation (VF) and contractile failure.Sodium pump inhibition was effected either by reducing the perfusate K concen-^ration (Kq) to 1.1 mmol. 1“’' or zero, or by including luraol.l ’ ouabain in the control medium (K<, = 4.9 mmol. 1 ’). A reduced Kg or ouabain produced a progressive net cellular K loss,net cellular gains in Na and Ca,and qualitatively similar declines in ATP and CP.These studies indicated primary roles for Ca accumulation and high-energy phosphate depletion in the mechanisms underlying the production of VF and contractile failure.The onset of VF was not related to any critical K loss,Na gain,or decline in high-energy phosphates. Reducing the extracellular Ca concentration from.2.5 to 0.5 mmol. 1 I in the presence of Llmmol.r’ prevented VF,Ca overload,depletion of ATP and CP,and markedly attenuated the deterioration in contractile function.However, a large K loss and Na gain were not prevented.These findings further suggested roles for Ca accumulation and high-energy phosphate depletion in the electrical and mechanical dysfunction produced by sodium pump blockade and indicated that the deterioration in cardiac energy metabolism was Ca-mediated. The antifibrillatory action of 0.51 and 2.04 umol. I"’ verapamil in- hearts perfused with ouabain, and 2.04 umol. 1"’ verapamil in preparations exposed to 1.1 mmol. 1“'' correlated with the drug's ability to preserve ATP and CP. This protective action on cardiac energy metabolism was not mediated by an inhibition of Ca accumulation or by a marked reduction in ATP utilization.Experiments performed with 0.51 umol. 1“'' verapamil and 1.1 mmol. I”'' K„ indicated that the higher drug concentration may possess antiarrhythmic properties independent of its effects on cardiac energy metabolism.