(Circulation. 1996;93:356-364.)
© 1996 American Heart Association, Inc.
Articles |
Increased Release of NO During Ischemia Reduces Myocardial Contractility and Improves Metabolic Dysfunction
Presented in part at the 44th Annual Scientific Session of the American College of Cardiology, New Orleans, La, March 19-22, 1995.
From the First Department of Medicine, the First Department of Physiology (H.K.), and the Department of Pathophysiology (M.T.), Department of Information Science, Osaka University School of Medicine, Osaka, Japan.
Correspondence to Masafumi Kitakaze, MD, PhD, First Department of Medicine, Osaka University School of Medicine, 2-2 Yamadaoka, Suita 565, Osaka, Japan.
Background We have reported that myocardial ischemia increases nitric oxide (NO) production. Several lines of evidence suggest that NO reduces myocardial contraction. Therefore, we tested whether endogenous NO decreases the inotropic response of the ischemic myocardium and whether endogenous NO is beneficial in the metabolic function of ischemic myocardium.
Methods and Results The left anterior descending coronary artery was perfused with blood from the left carotid artery in 72 dogs. An infusion of NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthase, did not affect fractional shortening (FS) under nonischemic conditions. After reduction of perfusion pressure so that coronary blood flow decreased to 60% of the control value, FS of the perfused area decreased, and intravenous infusion of isoproterenol increased FS. Before and during intravenous infusion of isoproterenol under conditions of coronary hypoperfusion, FS was significantly increased in the L-NAME group compared with the untreated group. Both lactate extraction ratio and the pH in coronary venous blood were significantly lower in the L-NAME–treated group than in the untreated group during coronary hypoperfusion. Infusion of L-arginine prevented the effects of L-NAME in the ischemic myocardium.
Conclusions These results indicate that endogenous NO reduces myocardial contractile function and improves myocardial metabolic function in the ischemic heart. The myocardial energy–sparing effect as well as coronary vasodilation due to NO may be beneficial to the ischemic myocardium.
Key Words: myocardial contraction • ischemia • L-NAME • nitric oxide • receptors, adrenergic
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