Does acute improvement of endothelial dysfunction in coronary artery disease improve myocardial ischemia? A double-blind comparison of parenteral D- and L-arginine.

OBJECTIVES

Parenteral L-arginine will improve myocardial ischemia in patients with obstructive coronary artery disease.

BACKGROUND

Endothelial dysfunction causes coronary arterial constriction during stress, and L-arginine improves endothelial dysfunction.

METHODS

Twenty-two patients with stable coronary artery disease and exercise-induced ST-segment depression underwent assessment of forearm endothelial function with acetylcholine and symptom-limited treadmill exercise testing during dextrose 5% infusion and after double-blind intravenous administration of L- and D-arginine (5 mg/kg/min) for 20 min.

RESULTS

Forearm blood flow increased with both L- and D-arginine (33%+/-6% and 38%+/-7%, respectively, p < 0.001). Acetylcholine-mediated forearm vasodilation also improved with both L- and D-arginine (p < 0.0001). The magnitude of improvement was similar with both enantiomers and was observed in patients throughout the range of acetylcholine responses and cholesterol levels. Heart rate and blood pressure at rest and during each stage 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 with both enantiomers.

CONCLUSIONS

Parenteral arginine produces non-stereo-specific peripheral vasodilation and improves endothelium-dependent vasodilation in patients with stable coronary artery disease by stimulation of insulin-dependent nitric oxide release or by nonenzymatic nitric oxide generation. Despite enhanced endothelial function, there was no improvement in myocardial ischemia during stress with either enantiomer. Whether parenteral arginine will be of therapeutic benefit in acute coronary syndromes and oral arginine in myocardial ischemia needs to be studied further.