FACTORS INFLUENCING QUINIDINE-INDUCED CHANGES IN EXCITABILITY AND CONTRACTILITY

¹ Department of Pharmacology, School of Medicine, University of Washington, Seattle, Washington

The effects of beat interval, drug concentration, time after exposure to the drug, sodium concentration ([Na]) and calcium concentration ([Ca]) on quinidine-induced changes in excitability and contractility were studied in isolated rabbit atrium with rate controlled by electrical stimulation. Quinidine produced a positive or a negative inotropic effect depending upon the frequency of stimulation, the concentration of quinicline and the time of measurement after the administration of quinidine. The positive inotropic effect of quinidine was greater at long beat intervals. In a concentration of 50 µg/ml, quinidine induced positive inotropism characterized by an increase in the degree of activation, by no change in the duration of activation and by no effect on the production or decay of positive inotropic effect of activation. The negative inotropic effect of quinidine was greater at short beat intervals and high concentrations of quinidine. It was temporarily reversed by increasing the stimulus intensity and decreasing the beat interval. Quinidine-induced inotropism was not dependent on the [Ca]/[Na]² ratio per se, but it was more nearly related to the absolute concentrations of these ions at a given [Ca]/[Na]². The time of onset of alternation in contractile force (i.e., excitability changes) produced by quinidine was inversely related to the frequency of stimulation and to the concentration of drug. Quinidine-induced onset of alternation was timedependent at long beat intervals and beat-or frequency-dependent at short beat intervals. The time of onset of alternation produced by quinidine was increased by high [Ca] and low [Na] and was inversely related to the [Ca]/[Na]² ratio. These results are compatible with an interaction between quinidine, Na and Ca for an active binding site in the excitable membrane.