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

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.

The Characteristics and Risk Factors of Coronary Artery Spasm Induced by Acetylcholine

BACKGROUND: Although there have been many studies on the risk factors for coronary artery disease, the etiology and risk factor of coronary artery spasm has not yet been determined. The objective of this study was to examine the risk factors for coronary vasospasm through a comparison of patients with angiographically determined vasospastic angina and patients without vasospasm and normal coronary artery. METHODS: Intracoronary injection of acetylcholine in order (20microg, 50microg, 100microg) were administered to all patients (Total 81:34 males, 47 females : mean age 50 years) who had a history of chest pain with normal or near normal coronary arteriographic fingings. After documentation of vasospasm in major epicardial coronary arteries by acetylcholine (Ach)-provocated dcoronary angiography, various risk factors (smoking, hypertension, diabetes, drinking and hyperlipidemia) were compared between patients with vasospasm and patients without vaspasm. RESULTS: 24 patients showed significant luminal narrowing (> or =75%)(Vasospasm group) and 57 patients showed no significant change (Control). Vasospasm group were suffered from typical chest pain in 92% of patients but control complained typical chest pain in 51% of subjects. The sites of vasoconstriction induced by Ach were LAD (11 cases), LCX (4 cases), RCA (11 cases) and vasoconstriction occurred 2 vessels (LAD and LCx) at the same time in two cases. The amount of Ach to provocate vasoconstriction was 20~50microg (90%) and there were no difference between left and right coronary arteries. The ratio of smoker was more frequent in the vasospasm group than control (58.3% vs 30.4%, p=0.046). But total cholesterol, low density lipoprotein, high density lipoprotein, triglycerides, apolipoprotein A, apolipoprotein B, lipoprotein (a), diabetes and body mass index, drinking were not statistically significant between two groups. CONCLUSION: Smoking appears to be a major risk factor for vasospastic angina by endotheilal dysfunction without significant coronary artery narrowing. But other fisk for coronary artery disease may not contribute to coronary vasospasm.