NITRIC-OXIDE DOES NOT MEDIATE CORONARY VASODILATION BY ISOFLURANE

Background: Isoflurane causes vasodilation in the coronary circulation . The current study employed a canine model permitting selective intra coronary administrations of isoflurane (1) to test the hypothesis that coronary vasodilation by isoflurane is mediated by nitric oxide and ( 2) to evaluate the persistence of coronary vasodilation during an exte nded exposure to isoflurane. Methods: Open-chest dogs anesthetized wit h fentanyl and midazolam were studied. The left anterior descending co ronary artery (LAD) was perfused via extracorporeal system with normal arterial blood or with arterial blood equilibrated with 1.4% (1 MAC) isoflurane. In the LAD bed, coronary blood now (CBF) was measured with an electromagnetic flowmeter and used to calculate myocardial oxygen consumption (MV(O2)) in series 1, performed at constant coronary perfu sion pressure (CPP), the LAD was exposed to 3 h of isoflurane in two g roups of eight dogs: control group, normal coronary endothelium; and e xperimental group, intracoronary infusion of the nitric oxide synthase inhibitor L-NAME (0.15 mg/min for 30 min). Series 2 was performed wit h CBF constant; thus, CPP varied directly with coronary vascular resis tance, In this series, initial steady-state changes in CPP by isoflura ne were evaluated in the same four dogs before and after L-NAME. Resul ts: In the control group of series 1, isoflurane caused a maximal, ini tial increase in CBF of 444%; however, CBF decreased progressively rea ching a value not significantly different from baseline after 3 h of i soflurane. Isoflurane caused a significant (approximately 35%) decreas e in MV(O2), which persisted during the 3-h administration. Findings a fter L-NAME (experimental group) were not significantly different from those in control group. In series 2, isoflurane caused significant de creases in CPP that were not affected by L-NAME. Conclusions: The lack of effect of L-NAME on isoflurane-induced coronary vasodilation sugge sts that nitric oxide does not mediate this response. The increase in CBF during prolonged isoflurane waned over time, perhaps because of ta chyphylaxis or emergence of a competitive vasoconstrictor mechanism, e .g., metabolic factors secondary to reduced oxygen demands.