Nitric oxide, an important regulator of perfusion-contraction matching in conscious pigs

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 279; no. 1; pp. H451 - H456
• Main Authors: Kudej, Raymond K, Kim, Song-Jung, Shen, You-Tang, Jackson, John B, Kudej, Amelia B, Yang, Gui-Ping, Bishop, Sanford P, Vatner, Stephen F
• Format: Journal Article
• Language: English
• Published: United States 01.07.2000
• Subjects: Animals; Coronary Circulation - drug effects; Coronary Circulation - physiology; Coronary Disease - physiopathology; Hemodynamics - drug effects; Hemodynamics - physiology; Myocardial Contraction - drug effects; Myocardial Contraction - physiology; Myocardial Ischemia - pathology; Myocardial Ischemia - physiopathology; Myocardial Reperfusion; Myocardial Stunning - physiopathology; Necrosis; Nitric Oxide - physiology; Nitric Oxide Synthase - antagonists & inhibitors; Nitroarginine - pharmacology; Space life sciences; Swine; Non-programmatic
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.2000.279.1.h451

1  Henry Hood Research Program, Weis Center for Research, Pennsylvania State University College of Medicine, Danville 17822; Department of Cellular and Molecular Physiology and 2  Department of Comparative Medicine, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033; and 3  Merck Research Laboratories, West Point, Pennsylvania 19486 We examined whether nitric oxide (NO) inhibition during moderate reduction in coronary blood flow (CBF) would affect perfusion-contraction matching. Coronary stenosis (CS) was induced in conscious pigs, which resulted in a stable 39 ± 1% reduction in CBF for 1.5 h. Ischemic zone wall thickening (IZWT) decreased by an average of 56 ± 2% during CS from 2.7 ± 0.2 mm. After reperfusion, myocardial stunning was observed, but this recovered without evidence of necrosis. After recovery and subsequent administration of systemic NO synthase inhibition ( N -nitro- L -arginine, 25 mg · kg 1 · day 1  × 3 days), CS for 1.5 h reduced CBF similarly but decreased IZWT significantly more, P  < 0.05, by 89 ± 5%. Myocardial stunning, i.e., the decrease in IZWT at 12 h post-CS, was more severe ( 65   ± 5% vs. 21 ± 3%), P  < 0.05. Furthermore, CS during NO synthase inhibition resulted in multifocal subendocardial areas of necrosis in the area at risk. These data suggest that in the intact, conscious pig, NO inhibition prevents perfusion-contraction matching, resulting in intensification of post-ischemic stunning and development of subendocardial necrosis. myocardium; ischemia; infarction; stunning