DOES THE ANTIARRHYTHMIC EFFECT OF ISCHEMIC PRECONDITIONING IN RATS INVOLVE THE L-ARGININE NITRIC-OXIDE PATHWAY

Ischemic preconditioning (PC) has been shown to limit ischemia- and re perfusion-induced arrhythmias. We wished to determine whether the anti arrhythmic effect of PC would be affected by inhibition of the L-argin ine nitric oxide (NO) pathway in anesthetized rats. Ischemia and reper fusion were produced by occlusion and release of a snare around the le ft coronary artery in all rats. The effect of PC (three cycles of 2-mi n coronary artery occlusion and 5-min reperfusion) on development of r eperfusion-induced arrhythmias after 5-min coronary artery occlusion w as studied in 12 rats. In 24 other rats, the specific NO synthesis inh ibitor N-G-monomethyl-L-arginine (L-NMMA 10 mg/kg, n = 12) or the musc arinic receptor antagonist-NO synthesis inhibitor nitro-L-arginine met hyl ester (L-NAME 10 mg/kg, n = 12), was administered intravenously (i .v.) before PC. In control groups, solvent (n = 15), L-NAME (10 mg/kg i.v., n = 12), L-NMMA (10 mg/kg i.v., n = 12), or L-arginine (L-Arg 10 0 mg/kg i.v., n = 12) was administered to rats 5 min before coronary a rtery occlusion without PC. PC significantly reduced the incidence of ventricular premature beats (VPBs) from 100% in the non-PC solvent gro up to 17%, decreased the incidence of ventricular tachycardia (VT) fro m 93 to 8%, and abolished the incidence of reversible and irreversible ventricular fibrillation (RVF and IVF: 87 and 47% in the non-PC solve nt group, respectively). L-NAME and L-NMMA did not significantly affec t the protective effect of PC on reperfusion-induced arrhythmias. Neit her L-NAME, L-NMMA, nor L-Arg administered in non-PC animals significa ntly influenced reperfusion-induced arrhythmias. Generation of NO thro ugh the L-Arg pathway appears not to be involved in the protective eff ect of PC against reperfusion-induced arrhythmias in rats.