Carnitine Deficiency Increases Susceptibility to Bupivacaine-induced Cardiotoxicity in Rats

Abstract

Background Anecdotal reports suggest that carnitine deficiency increases susceptibility to bupivacaine-induced cardiotoxicity. Bupivacaine inhibits lipid-based respiration in myocardial mitochondria via inhibition of acylcarnitine exchange in rats. The authors hypothesized that carnitine deficiency increases susceptibility to bupivacaine-induced asystole in rats and that acute repletion with L-carnitine reverses this effect. Methods Thirty male Sprague-Dawley rats were assigned to three groups. Rats assigned to the L-carnitine-deficient and L-carnitine-replete groups received subcutaneous D-carnitine on the 10 d before the experiment to induce L-carnitine deficiency. Control rats received an equal volume of subcutaneous normal saline. The rats were anesthetized and mechanically ventilated. Bupivacaine was infused intravenously at a rate of 2.0 mg · kg⁻¹ · min⁻¹ until asystole occurred. The L-carnitine-replete group received intravenous L-carnitine 100 mg · kg⁻¹ immediately before bupivacaine infusion. At asystole, blood was sampled to measure bupivacaine concentration. The primary outcome was time to asystole. Results L-carnitine deficiency significantly decreased survival duration (P < 0.0001). Time to bupivacaine-induced asystole decreased by 22% (P < 0.05) in the L-carnitine-deficient group (847 s [787-898]) (median [interquartile range]) compared with controls (1,082 s [969-1,427]). Intravenous administration of L-carnitine completely reversed the reduction in time to asystole. At asystole, the median plasma bupivacaine concentration in the L-carnitine-deficient group was 38% (P < 0.05) less than that in control animals. Plasma bupivacaine concentration was similar in L-carnitine-replete and control animals. Conclusions Carnitine deficiency increased sensitivity to bupivacaine-induced asystole, an effect that was reversed completely by L-carnitine repletion. This study suggests that carnitine deficiency may predispose to bupivacaine-induced cardiotoxicity. L-carnitine may have a protective role against bupivacaine cardiotoxicity.