Effects of lidocaine on myocardial contractility and baroreflex control of heart rate in conscious dogs

Abstract

The effects of intravenous lidocaine (30 and 60 micrograms X kg-1 X min-1 during 30 min) at steady-state plasma levels (1.9 +/- 0.2 and 3.5 +/- 0.2 micrograms/ml, respectively) were investigated in conscious dogs, previously instrumented for measurements of arterial and left ventricular (LV) pressures, isometric myocardial contractility indexes (LV peak rate of tension development [dP/dt] and LV [dP/dt]/DP40), and heart rate. In addition, before and at the end of lidocaine infusions, arterial baroreflex responses were tested by bolus injections of nitroglycerin and phenylephrine. Whereas LV peak dP/dt and LV (dP/dt)/DP40 were significantly decreased after the low dosage of lidocaine, these indexes returned to control values after the 10th min of infusion of the high dosage. Moreover, eight out of 14 dogs exhibited continuous tremors, tachycardia, hypertension, and increase in contractility after the 10th min of lidocaine infusion (60 micrograms X kg-1 X min-1), although their lidocaine plasma levels (3.7 +/- 0.2 micrograms/ml) did not differ from those of the whole group. When these dogs were pretreated by combined alpha- and beta-adrenoceptor blocking drugs, none of them had tremors, and there was a constant depressant effect on cardiac chronotropism and inotropism. A specific enhancement of baroreflex sensitivity after phenylephrine injection was observed at the high lidocaine dosage. It is concluded that a central stimulation of both components of the autonomic nervous system modulates the direct effects of therapeutic plasma levels of lidocaine on cardiac chronotropism and inotropism in conscious dogs.