Effect of L-Arginine on Post-Ischemic Myocardial and Vascular Stunning in Open-Chest Dogs

ABSTRACT

BACKGROUND: Although recent studies have demonstrated that infusion of L-arginine reduces myocardial necrotic area during prolonged ischemia, its effects on transient postischemic myocardial dysfunction(myocardial stunning) and microvascular dyfunction(vascular stunning) are not well known. To investigate whether intravenous administration of L-arginine, physiological nitric oxide(NO) precursor, during reperfusion would attenuate postischemic myocardial dysfunction and microvascular dysfunction, 15 open-chest dogs were studied. METHODS: In 15 pentobarbital anesthesized open-chest dogs, left circumflex coronary artery was occluded for 20 minutes and was followed by a reperfusion for 60 minutes. L-Arginine(30mg/kg)(L-arginine group, n=8) or saline(control group, n=7) was given intravenously by a bolus 1 minute before reperfusion and was followed by a continuous infusion(10mg/kg/min) for 30 minutes during reperfusion. Before coronary occlusion and 60 minutes after reperfusion, coronary blood flow(CBF) and coronary vascular resistance(CVR) wre measured after intracoronary injection of each of acetylcholine(0.01/kg) and adenosine(1.5/kg), and reactive hyperemia with coronary occlusion(RH20) for 20 seconds was measured. Myocardial segment thickening in the area of ischemia-reperfusion was measured using 2D-echocardiography. The echocardiographic images were digitized and analyzed by cardiac image analyzer. RESULTS: The results obtained 60 minutes after reperfusion were as follows. 1) CBF was decreased by 41% in L-arginine group vs 30.1% in control group(p < 0.05) and CVR was increased by 83.9% in L-arginine group vs 19.3% in control group after 60 minutes of reperfusion, compared with pre-occlusion baseline values. 2) Percent change of CBF was decreased in control group(acetylcholine by 25.8%, adenosine by 29.2%, RH20 by 39.8%), while it was increased in L-arginine group(acetylcholine by 60%, adenosine by 22%, RH20 by 26.7%). Percent change of CVR was increased in control group(acetylcholine by 10.5%, adenosine by 6.9%, RH20 by 21%), but it was decreased in L-arginine group(acetylcholine by 10%, adenosine by 6.6%, RH20 by 1.6%). Increase of CBF and decrease of CVR were significant on acetylcholine and RH20 between control group and L-arginine group. 3) Fraction of myocardial segment thickening was significantly decreased in L-arginine group(by 80%) compared with control group(by 61.7%, p < 0.05). CONCLUSIONS: The finding that L-arginine depressed post-ischemic myocardial contractil function suggests that systemic infusion of L-arginine has unfavorable effect on myocardial stunning. In contrast, the finding that L-arginine improved CBF and CVR with acetylcholine and adenosine and reactive hyperemia indicates that L-arginine may exert a beneficial effect on vascular stunning. These results suggest that L-arginine may have independent effects on myocardial stunning and vascular stunning.