Abstract
Interactions of potassium and antiarrhythmic agents on ventricular myocardial electrophysiology were studied in 25 isolated, perfused rabbit hearts by utilizing an intracellular microelectrode technic. Perfusion of quinidine (0.01 mg./ml.) in a normal concentration of potassium (5.6 mEq./L.) caused a significant decrease in the maximal rate of depolarization (−69.1%), heart rate (−40.4%) and the action potential duration per unit of time (−13.8%). Reduction in the height of action and resting potentials was insignificant. Lowering potassium to 0.8 mEq./L., in the presence of the same concentration of quinidine, significantly increased the maximal rate of depolarization (+82.5%), the height of action potential (+8.5%) and resting potential (+9.9%). The action potential duration per unit of time also showed a significant increase (+15.2%) to control value, although the heart rate was further decreased. Initial perfusion of a low potassium solution caused a significant increase in the height of action potential (+3.3%) and resting potential (+7.0%) as well as a significant decrease in the action potential duration per unit of time (−19.2%). The maximal rate of depolarization and the heart rate showed no significant changes. Addition of quinidine to this low potassium perfusate did not produce any appreciable changes in the maximal rate of depolarization, or in the height of action and resting potentials. The action potential duration per unit of time again returned to its control level. Hence, the electrophysiologic action of quinidine was nullified by a low potassium concentration in both groups of experiments. Quite a similar antagonism was demonstrated between low potassium concentration and other antiarrhythmic agents (antazoline and SU-11636), while high potassium concentration (12 mEq./L.) enhanced the depressive effects of these three drugs. The electrophysiologic mechanism of antiarrhythmic agents was discussed, and the clinical importance of controlling serum potassium concentration during the administration of these agents was suggested.
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