Coronary vascular injury following transient coronary artery occlusion: prevention by pretreatment with deferoxamine, dimethylthiourea and N-2-mercaptoproprionyl glycine.
The role of oxygen-derived free radicals as initiators of vascular dysfunction observed 24 hr after transient coronary artery occlusion (15 or 30 min) was examined in the anesthetized dog. A 15-min occlusion increased human serum (HSA) albumin extravasation within anterior myocardium without producing myocardial necrosis or edema. Minimal leukocyte uptake and free radical formation were present at 24 hr. 2-Mercaptoproprionyl glycine (MPG) (a free radical scavenger), deferoxamine (a chelator of ferrous ions) and dimethylthiourea (a hydroxyl ion scavenger), administered 15 min before coronary artery occlusion and extending 1.5 hr into reperfusion, reduced HSA uptake within anterior myocardium. A different pattern of injury was present after a 30-min occlusion. Subendocardial necrosis (1.2 +/- 0.8 g), edema, HSA extravasation and leukocyte uptake were observed at 24 hr. MPG failed to reduce the extent of necrosis, HSA extravasation, edema, leukocyte uptake or free radical formation. HSA extravasation, leukocyte uptake, tissue edema and free radical formation present 24 hr after a 30-min occlusion were reduced by acute deferoxamine and dimethylthiourea, but not by acute MPG administration. The failure of MPG to reduce HSA extravasation observed 24 hr after a 30-min coronary artery occlusion was associated with both leukocyte uptake and continued free radical formation, whereas dimethylthiourea and deferoxamine reduced leukocyte uptake, free radical formation and HSA extravasation.
Department of Pharmacology, University of Oklahoma Health Sciences Center, Oklahoma City.
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Patterson
D000818:Animals; D002199:Capillary Permeability; D003327:Coronary Disease / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology; D003676:Deferoxamine / Q000627:therapeutic use*; D004285:Dogs; D015227:Lipid Peroxidation; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012709:Serum Albumin / Q000493:pharmacokinetics; D013890:Thiourea / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D008625:Tiopronin / Q000627:therapeutic use*
D017382:Reactive Oxygen Species; D012709:Serum Albumin; C038983:1,3-dimethylthiourea; D008625:Tiopronin; D013890:Thiourea; D003676:Deferoxamine