Role of L-arginine-nitric oxide pathway in myocardial reoxygenation injury.
In view of the recent findings that NO reacts with superoxide anion to generate hydroxyl radical, the present study was conducted to ascertain the role of endogenous NO in mediating myocardial reoxygenation injury in the hypoxic piglet on cardiopulmonary bypass. Anesthetized piglets were made hypoxic (PaO2 = 20-30 mmHg) for up to 120 min, followed by reoxygenation on cardiopulmonary bypass for 30 min. Reoxygenation caused rapidly developing myocardial injury characterized by decreased contractility (expressed as end-systolic elastance) and increased lipid peroxidation (measured as conjugated dienes). Systemic venous and coronary sinus blood content of NO decreased significantly during hypoxia and increased substantially above prehypoxic levels during reoxygenation on cardiopulmonary bypass. Administration of either the antioxidants mercaptopropionyl glycine and catalase or the NO synthase inhibitor, NG-nitro-L-arginine methyl ester, to the extracorporeal circuit afforded similar and nearly complete protection against myocardial reoxygenation injury. The protective effects of NG-nitro-L-arginine methyl ester were nullified by adding an excess of L-arginine to the pump circuit, suggesting that the L-arginine-NO pathway is involved in myocardial reoxygenation injury.
Matheis
G
G
Department of Cardiothoracic Surgery, University of California, Los Angeles, School of Medicine 90024.
Sherman
M P
MP
Buckberg
G D
GD
Haybron
D M
DM
Young
H H
HH
Ignarro
L J
LJ
D000818:Animals; D000831:Animals, Newborn; D001120:Arginine / Q000097:blood / Q000378:metabolism*; D002315:Cardiopulmonary Bypass; D002374:Catalase / Q000494:pharmacology; D000860:Hypoxia / Q000097:blood / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000209:etiology*; D009206:Myocardium / Q000378:metabolism*; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D013552:Swine; D008625:Tiopronin / Q000494:pharmacology
D009569:Nitric Oxide; D001120:Arginine; D008625:Tiopronin; D002374:Catalase; D010100:Oxygen