L-carnitine increases survival in a murine model of severe verapamil toxicity

Objectives: l-Carnitine is an essential compound involved in cellular energy production through free fatty acid metabolism. It has been theorized that severe verapamil toxicity "shifts" heart energy production away from free fatty acids and toward other sources, contributing to profound cardiogenic shock. The primary study objective was to determine whether intravenous (IV) l-carnitine affects survival in severe verapamil toxicity. Secondary objectives were to determine the effects on hemodynamic parameters. The authors hypothesized that IV l-carnitine would increase both survival and hemodynamic parameters in severe verapamil toxicity. Methods: This was a controlled, blinded animal investigation. Sixteen male rats were anesthetized, ventilated, and instrumented to record mean arterial pressure (MAP) and heart rate. Verapamil toxicity was achieved by a constant infusion of 5 mg/kg/hr. After 5 minutes a bolus of 50 mg/kg of either l-carnitine or normal saline was given. The experiment concluded when either 10% of baseline MAP was achieved or 150 minutes had elapsed. The data were analyzed using Kaplan-Meier analysis, log rank test, and analysis of variance. Results: The median survival for the animals in the l-carnitine group was 140.75 minutes (interquartile range [IQR] = 98.6 to 150 minutes), and for those in the normal saline group it was 49.19 minutes (IQR = 39.02 to 70.97 minutes; p = 0.0001). At 15 minutes the MAP was 20.45 mm Hg greater in the animals in the l-carnitine group than in the animals in the normal saline group (95% confidence interval [CI] = 0.25 to 40.65; p = 0.047). Conclusions: When compared with saline, IV l-carnitine increases survival and MAP in a murine model of severe verapamil toxicity.