Protection by L-arginine against Epinephrine-induced Arrhythmia and Cardiotoxicity

Abstract

Nitric oxide is important in control of coronary blood flow, cardiomyocyte contractility, cardiac rhythm, and thrombogenicity. We aimed to investigate the effect of the nitric oxide precursor L-arginine on cardiac arrhythmia and myocardial injury induced by epinephrine in male Sprague-Dawley rats. The possible modulation of L-arginine effects by methylene blue (MethyB), a nitric oxide synthase inhibitor was also examined. Cardiac arrhythmia was induced with 10μg/kg epinephrine given intravenously (i.v.). L-arginine (200mg/kg) or L-arginine and MethyB (100mg/kg) were intraperitoneally (i.p.) administered prior to i.v. epinephrine. Other groups received i.p. saline, only L-arginine or only MethyB (100mg/kg). Results showed that compared with the saline control, epinephrine caused a significant bradycardia (188.7±24.4 vs. 405.6±1.19beats/min), increased QRS duration (0.039±0.006 vs. 0.0185±0.0001s), decreased R wave amplitude (0.18±0.01 vs. 0.23±0.011mv), and ventricular extrasystoles. L-arginine alone showed no significant effect on heart rate (380.8±10.0 vs. 405.6±1.19beats/min) but increased QRS duration (0.029±0.0002 vs. 0.0185±0.0001s), and R wave amplitude (0.47±0.01 vs. 0.23±0.011mv). L-arginine given prior to epinephrine prevented bradycardia, shortened the duration of arrhythmia and decreased the number of extrasystoles. The administration of L-arginine and MethyB almost completely suppressed epinephrine-induced ventricular arrhythmias. Epinephrine caused severe degeneration of muscle fibres, widening of intercellular spaces, cellular infiltrations and interstitial haemorrhage. L-arginine markedly attenuated, while L-arginine/MethyB completely prevented these changes. It is concluded that L-arginine protects against cardiac arrhythmias and cardiac tissue damage caused by epinephrine.