NITRIC OXIDE DOES NOT MEDIATE CORONARY VASODILATION DURING ACUTE NORMOVOLEMIC HEMODILUTION IN DOGS

Abstract

S72 INTRODUCTION: Acute normovolemic hemodilution (ANH) is accompanied by increases in coronary blood flow (CBF) that are attributable to the combined effects of reduced blood viscosity and vasodilation [1]. The mechanism for this vasodilation is unknown. While previous findings have implied that endothelium-derived nitric oxide (EDNO) is involved in the systemic vasodilation accompanying ANH [2], the role of this mechanism in the coronary circulation remains to be evaluated. Accordingly, the present study was performed to test the hypothesis that inhibition of EDNO by the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) would compromise myocardial perfusion during ANH. METHODS: After approval from the University Animal Care Committee, studies were conducted in ten open-chest dogs anesthetized with isoflurane and fentanyl. Measurements of myocardial blood flow (MBF) were obtained in the perfusion territories of the left anterior descending (LAD) and circumflex (CX) coronary arteries using radioactive microspheres. Mean aortic pressure (MAP), mean left atrial pressure (MLAP), and heart rate (HR) were measured using standard methods. A Doppler flow transducer was used to measure CBF in the LAD. Two groups were studied. In Group 1 (NOS Inhibition; n=5), the LAD region received an intracoronary (i.c.) infusion of L-NAME (4.5 mg), and the CX region served as a control. Effectiveness of L-NAME was demonstrated by the its ability to inhibit the increases in CBF by the endothelium-dependent coronary vasodilator acetylcholine (20 [micro sign]g/min, i.c.), while having no effect on those by the endothelium-independent coronary vasodilator sodium nitroprusside (80 [micro sign]g/min, i.c.). In Group 2 (Endothelium Intact; n=5), neither the LAD nor the CX region was treated with L-NAME. This was done to validate the use of the CX bed as a control for the LAD bed in Group 1. Data were obtained under baseline conditions (hematocrit; 40 +/- 2 %) and following ANH with 5% dextran-40 to an hematocrit of 20 +/- 1 %. RESULTS: ANH caused similar increases in MBF in LAD and CX regions, whether or not the LAD region was treated with L-NAME (Figure 1). ANH had no effect on MAP, MLAP, or HR.Figure 1DISCUSSION: Pretreatment with L-NAME did not compromise myocardial perfusion during ANH. This finding implies that EDNO does not mediate coronary vasodilation under this condition.