Endothelial dysfunction in myocardial ischemia and reperfusion: role of oxygen-derived free radicals.
Myocardial ischemia followed by reperfusion results in endothelial dysfunction in cats. This dysfunction is characterized by a loss of endothelium-derived relaxing factor (EDRF) release in response to endothelium-dependent dilators. This loss of endothelium-dependent relaxation (EDR) occurs significantly at 2.5 min post-reperfusion and the dysfunction progresses until it is complete at 20 min post-reperfusion. This reduced EDR is prevented by superoxide dismutase, but not by hydroxyl radical scavengers. In contrast, neutrophil accumulation in the heart, as measured by cardiac myeloperoxidase (MPO) activity, does not reach significant levels until 3 h post-reperfusion, and significant myocardial necrosis does not occur until 4.5 h post-reperfusion. No significant changes in EDR, MPO or cardiac necrosis occurred during the 90 min of ischemia. Thus, endothelial dysfunction is an early and specific marker of reperfusion injury preceding neutrophil involvement and cardiac necrosis. Superoxide radicals appear to play a key role in the decreased EDR observed early after reperfusion.
Lefer
A M
AM
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania.
Lefer
D J
DJ
D000818:Animals; D002415:Cats; D003327:Coronary Disease / Q000503:physiopathology*; D003331:Coronary Vessels / Q000502:physiology; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology*; D005609:Free Radicals; D006321:Heart / Q000503:physiopathology; D015425:Myocardial Reperfusion; D009336:Necrosis / Q000473:pathology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D009195:Peroxidase / Q000032:analysis; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism
D005609:Free Radicals; D013481:Superoxides; D009569:Nitric Oxide; D009195:Peroxidase; D013482:Superoxide Dismutase