Antiarrhythmic and arrhythmogenic effects of L-carnitine in ischemia and reperfusion.
Isolated rat hearts were subjected to 30-min coronary artery occlusion followed by 120-min reperfusion. The hearts (n=8-12) were perfused with Krebs-Henseleit solution enriched with L-carnitine (0.5, 2.5 and 5 mM) for 10 min before and after ischemia or reperfusion and for the whole period of ischemia and reperfusion. Two-hour perfusion with L-carnitine during ischemia/reperfusion markedly (p<0.05) and dose-dependently decreased the incidence of ventricular tachycardia (VT, maximum 65%). The incidence of reperfusion ventricular fibrillation (VF) also decreased from 63% (control) to 17% in hearts perfused with 5 mM L-carnitine, as reflected by a significant (p<0.05) decline in VF duration from 218+/-99 sec in control to 19+/-19 sec. Perfusion of etomoxir (palmitoylcarnitinetransferase-1 inhibitor) along with L-carnitine reversed the antiarrhythmogenic action of L-carnitine. Interestingly, short time preischemic administration of L-carnitine produced a concentration-dependent arrhythmogenic effects on both ischemia and reperfusion-induced arrhythmias. These results show that L-carnitine produced a protective effect against reperfusion arrhythmias only when it was perfused for the whole period of the experiment. This protective action was reversed by concomitant use of etomoxir, suggesting that the efficacy of L-carnitine is due to its mitochondrial action but cannot be solely attributed to increased fatty acid oxidation.
Najafi
M
M
Department of Pharmacology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
Garjani
A
A
Maleki
N
N
Eteraf Oskouei
T
T
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000503:physiopathology; D002331:Carnitine / Q000008:administration & dosage / Q000627:therapeutic use*; D054059:Coronary Occlusion / Q000188:drug therapy*; D004852:Epoxy Compounds / Q000627:therapeutic use; D005947:Glucose; D006321:Heart / Q000187:drug effects*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017180:Tachycardia, Ventricular / Q000188:drug therapy; D014325:Tromethamine; D014693:Ventricular Fibrillation / Q000188:drug therapy; D018879:Ventricular Premature Complexes / Q000188:drug therapy
D000889:Anti-Arrhythmia Agents; D004852:Epoxy Compounds; C074097:Krebs-Henseleit solution; D014325:Tromethamine; D005947:Glucose; C054207:etomoxir; D002331:Carnitine