Effects of lidocaine on isolated, blood-perfused ventricular contractility in the dog

Direct inotropic effects of lidocaine on ventricular muscle were investigated in isolated canine left ventricular preparations which were perfused with a donor dog's arterial blood. Intravenous administration of lidocaine in doses of less than 1 mg/kg did not cause any significant hemodynamic or cardiac changes in the donor dog and in the isolated ventricular preparation. A large dose of 10mg/kg of lidocaine produced a marked depressor response in the donor and a negative inotropic effect in the isolated ventricle. Direct injection of lidocaine (1-30 micromol) to the isolated preparation induced a dose-related decrease in the ventricular contractile force. Infusion of lidocaine (3 micromol/ml per min) did not influence norepinephrine- or calcium chloride-induced positive inotropic effects. In the frequency-force relationship, lidocaine generally depressed the contractility, exhibiting the positive staircase phenomenon. On the other hand, a calcium entry inhibitor, diltiazem, readily caused the negative staircase. From these results, it is concluded that (1) a large amount of lidocaine has a cardiac depressant property, (2) lidocaine has no antiadrenergic properties, and (3) the action of lidocaine may probably be due to the effect of intracellular calcium movement but not to a modification of Ca inward currents.