A mechanism of quinidine-induced changes in the contraction force of guinea-pig atria.

Abstract

The mechanisms modifying the isometric contraction force induced by 0.13–14 μg/ml quinidine concentrations were investigated on spontaneously beating and electrically stimulated atria excised from untreated and reserpinepretreated guinea-pigs. Quinidine produced typical changes in the depolarization, repolarization and conduction rates of atria. The measured characteristics of the transmembrane potentials were altered in a qualitatively similar degree, regardless whether quinidine action resulted in an increase, a decrease, or no change in contraction force. In electrically stimulated atria increasing concentrations of quinidine induce a dose-response related increase in contraction force whereas reserpine-pretreatment results in a diphasic change. In spontaneously beating atria increasing concentrations of quinidine do not change the contraction force but do so markedly after reserpine-pretreatment. It is suggested that quinidine induces changes in the contraction force by altering the frequency of spontaneously beating atria while simultaneously antagonizing the action of catecholamines. It has been recognized for some time that administration of quinidine to cardiac muscle dereases the depolarization [1–3], repolarization [4–6] and conduction [7] rates of action potentials and decreases contraction force [3,8–11]. Although many of these reports are based on the use of quinidine concentrations which may be considered toxic [12, 13], some reports indicate an initial increase in contraction force preceding depression [2, 3, 14]. When comparing the electropharmacological properties of pure quinidine and dihydroquinidine sulfate on electrically stimulated atria of guinea-pigs [15], we observed that there was always an increased contraction force if the drug concentration did not induce a persistent arrhythmia or abolish conducted events. We also found in addition to the typical changes of membrane characteristics, that the actions of quinidine on the contraction force of atria appears to be modified by stimulation frequency and catecholamines.