L-carnitine reduces susceptibility to bupivacaine-induced cardiotoxicity: an experimental study in rats

Abstract

These findings suggest that acute administration of L-carnitine 100 mg·kg decreases susceptibility to bupivacaine cardiotoxicity, but is ineffective during resuscitation from bupivacaine-induced cardiac arrest.

The osmo-metabolic approach: a novel and tantalizing glucose-sparing strategy in peritoneal dialysis

“…Similar findings were obtained in murine models of moderate carnitine deficiency induced with carnitine depleting agents such as pivalic acid, mildronate and d-carnitine [77][78][79]. We have shown that rats exposed to a moderate reduction in cardiac l-carnitine content are more susceptible to myocardial injury induced by β-adrenergic stimulation (isoproterenol) along with an unanticipated high mortality rate [77].…”

“…Indeed, l-carnitine supplementation of such l-carnitine deficient mice subjected to ascending aortic constriction not only prevented cardiac injury, but it also increased survival rate compared to untreated mice. A moderate heart carnitine deficiency induced by d-carnitine treatment increased sensitivity to bupivacaine-induced asystole, whereas l-carnitine repletion completely reversed such effect [78]. This experimental study was conducted by the same authors after they experienced a case of peri-operative cardiac arrest in a carnitine deficient child (valproate-induced) in the context of intravascular administration of bupivacaine, an anaesthetic known to exert cardiotoxic side effects [78].…”

Lipid Emulsion for Treating Local Anesthetic Systemic Toxicity

“…In 1997, Weinberg et al reported that subcutaneous injection of a small dose of bupivacaine (non-toxic dose: 22 mg) in a 16-year-old female patient with isovaleric acidemia yielded unexpected ventricular arrhythmia likely caused by secondary systemic carnitine deficiency 7 . Based on these reports, this unexpected ventricular arrhythmia was likely associated with increased susceptibility to bupivacaine toxicity due to carnitine deficiency 7 - 11 . In addition, Wong et al reported ventricular arrhythmia caused by the presumed intravascular migration of an epidural catheter in a 6-year-old male patient with both secondary carnitine deficiency due to long-term treatment with valproic acid and a non-toxic dose of bupivacaine (0.58 mg/ml) 12 .…”

“…Bupivacaine prevents long-chain fatty acid transport to the mitochondria by inhibiting carnitine-acylcarnitine translocase 8 - 10 . Pretreatment with L-carnitine before bupivacaine-induced asystole in rats decreased the susceptibility to bupivacaine-induced cardiac toxicity 11 . In 1997, Weinberg et al reported that subcutaneous injection of a small dose of bupivacaine (non-toxic dose: 22 mg) in a 16-year-old female patient with isovaleric acidemia yielded unexpected ventricular arrhythmia likely caused by secondary systemic carnitine deficiency 7 .…”

Combination of vitamin E and L-carnitine is superior in protection against isoproterenol-induced cardiac injury: histopathological evidence

“…GIII: in which rats were subcutaneously injected with isoproterenol with same dose and duration plus vitamin E (100 IU/kg BW) intraperitoneal injection daily for 4 weeks according to Gayathri et al, [8]. GIV: in which rats were subcutaneously injected with isoproterenol plus intraperitoneal daily injection of L-carnitine (100 mg/kg BW) for 4 weeks according to Wong et al [33].…”