Cardiovascular actions of mixidine fumarate

Mixidine has been reported to slow the heart rate without decreasing the force of myocardial contraction. In view of force-frequency relationships, it may have a ‘masked’ positive inotropic action which counter-balances the decrease in the force of contraction secondary to its cardiac slowing effect. Thus, the effect of this compound on the mammalian cardiovascular system was examined in several heart preparations. Mixidine reduced heart rate in anesthetized cats with a transient increase in blood pressure. In spontaneously beating Langendorff preparations of guinea-pig heart and in canine heart-lung preparations, it caused a sustained decrease in the heart rate with a concomitant decrease in force of contraction. In right atrial preparations of guinea-pig heart, however, the mixidine-induced fall in heart rate was not accompanied by changes in force of contraction. In electrically stimulated left atrial preparations of guinea-pig heart and canine heart-lung preparations, mixidine produced a positive inotropic effect. The inotropic effect observed in guinea-pig atrial preparations was not influenced by a concentration of propranolol which could significantly shift the concentration-response curve for isoproterenol. The positive inotropic effect of mixidine observed in canine heart-lung preparations was greater when it was given into left atrium, bypassing pulmonary circulation, or in preparations depressed with pentobarbital. These results indicate that mixidine has a positive inotropic effect in addition to its cardiac slowing action. Thus, the net effect of this drug on force of myocardial contraction depends on the relative contributions of the direct positive inotropic effect and an indirect negative inotropic effect secondary to cardiac slowing. A compound which has these properties may be useful in treating ischemic heart disease.