Analysis of onset mechanism for lithium carbonate-induced cardiovascular adverse events assessed in the halothane-anesthetized dogs

Abstract

Introduction: Lithium has been widely used for the treatment of bipolar disorder. However, several cardiac adverse events have been noticed in patients who were also treated with other drugs in addition to lithium. In the present study, we studied the effects of lithium by itself to precisely analyze the onset mechanisms of its cardiovascular adverse events.

Methods: We intravenously administered lithium carbonate in doses of 0.1, 1 and 10 mg/kg/10 min to the halothane-anesthetized dogs (n=4) under the monitoring of cardiohemodynamic and electrophysiological variables.

Results: The currently used doses of lithium provided plasma concentrations ranging from sub-therapeutic to toxic ones. The low and middle doses significantly prolonged the ventricular effective refractory period. Additionally, the high dose significantly decreased the heart rate, delayed the intraventricular conduction and the ventricular repolarization, and kept the effective refractory period prolonged.

Conclusion: Lithium may have a wide safety margin against hemodynamic adverse events excpt that it can moderately inhibit both Na⁺ and K⁺ channels, leading to increase of the ventricular refractoriness and decrease of the heart rate.