744-1 Endogenous Nitric Oxide Attenuates Myocardial Inotropic Responses in Ischemic Myocardium of the Canine Heart

Abstract

Nitric oxide (NO) is reported to attenuate myocardial contraction, raising the possibility that endogenous NO decreases the inotropic response of ischemic myocardium. In 42 dogs, the left anterior descending coronary artery was perfused with blood from the left carotid artery. During reduction of perfusion pressure (1 03 ± 6 to 53 ± 4 mmHg) so that coronary blood flow (CBF) decreases to 60% of the control, fractional shortening (FS) of the perfused area decreased from 23.3 ± 3.3 to 8.4 ± 1.3%. Intravenous infusions of isoproterenol (ISO, 75 and 150 ng/kg/min) increased FS to 15.9 ± 33 and 22.5 ± 2.5%, respectively. An infusion of L-NAME, an inhibitor of NO synthase, did not alter FS in the non-ischemic condition (24.5 ± 2.1%). However, changes in FS due to reduction of C8F to 60% (FS:14.3 ± 1.3%), and intravenous infusions of ISO during coronary hypoperfusion (FS:23.3 ± 3.3 and 32.3 ± 2.8%) were augmented in the L-NAME group compared with the untreated group. Lactate extraction ratio (-4.1 ± 2.2 vs -15.6 ± 4.2%), and pH in the coronary venous blood (7.32 ± 0.03 vs 7.27 ± 0.03) in the L-NAME group were lower than the untreated group during coronary hypoperfusion. Furthermore, L-arginine restored metabolic dysfunction due to L-NAME in the ischemic myocardium. These results indicate that endogenous NO attenuates myocardial contractile function in the ischemic heart and improves myocardial metabolic function. NO and NO donors such as nitrates in the ischemic heart disease may play an importrant role for myocardial energysparing effect as well as coronary vasodilation.