Published online before print September 25, 2003, doi: 10.1161/01.RES.0000097762.64561.D2
© 2003 American Heart Association, Inc.
Integrative Physiology |
Cardiac Nerves Affect Myocardial Stunning Through Reactive Oxygen and Nitric Oxide Mechanisms
From the Cardiovascular Research Institute (C.-H.H., S.F.V., A.P.P., G.Y.), Department of Cell Biology and Molecular Medicine, UMDNJ–New Jersey Medical School, Newark, NJ; Department of Surgery (C.-H.H.), National Yang-Ming University School of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Clinical Sciences (R.K.K.), Tufts University School of Veterinary Medicine, North Grafton, Mass.
Correspondence to Raymond K. Kudej, DVM, PhD, FAHA, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Cardiovascular Research Institute, 185 S Orange Ave, MSB-G609, Newark, NJ 07101. E-mail Raymond.Kudej{at}tufts.edu
The goal of this study was to investigate the role of cardiac nerves on the response to 90-minute coronary artery stenosis (CAS), which reduced coronary blood flow by 40% for 90 minutes, and subsequent myocardial stunning after reperfusion in chronically instrumented conscious pigs. In pigs with regional cardiac denervation (CD), myocardial stunning was intensified, ie, at 12 hours reperfusion wall thickening (WT) was depressed more, P<0.05, in CD (-46±5%) as compared with intact pigs (-31±3%) and remained depressed in CD at 24 hours reperfusion (-45±6%). Although the TTC technique was negative for infarct, histopathological analysis revealed patchy necrosis present in 11±2% of the area at risk. In intact pigs, WT had essentially recovered at 24 hours without infarct. In CD pigs treated with either an antioxidant, N-2-mercaptopropionyl glycine (MPG, 100 mg/kg per hour) or systemic nitric oxide synthase inhibition using N
-nitro-L-arginine (L-NA, 30 mg/kg for 3 days), recovery of wall thickening was similar to that in pigs with intact nerves and without evidence of infarct. Immunohistochemistry analysis for 3-nitrotyrosine in tissue after CAS and 1 hour reperfusion demonstrated enhanced peroxynitrite-related protein nitration in pigs with regional CD compared with pigs with intact cardiac nerves, and pigs with regional CD and MPG or L-NA. Thus, reperfusion after myocardial ischemia in the setting of CD results in enhanced stunning and development of infarct. The underlying mechanism appears to involve nitric oxide and reactive oxygen species.
Key Words: cardiac denervation • coronary stenosis • myocardial stunning • reactive oxygen species
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