DOES ACUTE IMPROVEMENT OF ENDOTHELIAL DYSFUNCTION IN CORONARY-ARTERY DISEASE IMPROVE MYOCARDIAL-ISCHEMIA - A DOUBLE-BLIND COMPARISON OF PARENTERAL D-ARGININE AND L-ARGININE

Objectives. Parenteral L-arginine will improve myocardial ischemia in patients with obstructive coronary artery disease. Background. Endothe lial dysfunction causes coronary arterial constriction during stress, and L-arginine improves endothelial dysfunction, Methods. Twenty-two p atients with stable coronary artery disease and exercise-induced ST-se gment depression underwent assessment of forearm endothelial function with acetylcholine and symptom-limited treadmill exercise testing duri ng dextrose 5% infusion and after double blind intravenous administrat ion of L- and D-arginine (5 mg/kg/min) for 20 min. Results, Forearm bl ood flow increased with both L- and D-arginine (33% +/- 6% and 38% +/- 7%, respectively, p < 0.001). Acetylcholine-mediated forearm vasodila tion also improved with both L- and D-arginine (p < 0.0001). The magni tude of improvement was similar with both enantiomers and was observed in patients throughout the range of acetylcholine responses and chole sterol levels. Heart rate and blood pressure at rest and during each s tage of exercise and exercise duration remained unchanged with L- and D-arginine compared to control. Ischemic threshold, measured either as the rate-pressure product or the duration of exercise at the onset of 1-mm ST-segment depression during exercise, also remained unchanged. Serum arginine, insulin and prolactin levels (p < 0.01) increased dth both enantiomers, Conclusions. Parenteral arginine produces non-stereo specific peripheral vasodilation and improves endothelium dependent v asodilation in patients with stable coronary artery disease by stimula tion of insulin dependent nitric oxide release or by non-enzymatic nit ric oxide generation. Despite enhanced endothelial function, there was no improvement in myocardial ischemia during stress dth either enanti omer, Whether parenteral arginine will be of therapeutic benefit in ac ute coronary syndromes and oral arginine in myocardial ischemia needs to be studied further. (C) 1998 by the American College of Cardiology.