Bucillamine prevents myocardial reperfusion injury.
Injury during reperfusion can partially offset the benefit of relief of ischemia in myocardial infarctions rapidly treated with thrombolytic drugs or angioplasty. We assessed whether bucillamine (N-[2-mercapto-2-methylpropionyl]-L-cysteine) is potentially useful to treat myocardial reperfusion injury. Bucillamine is a potent sulfhydryl donor not previously tested as a treatment of reperfusion injury. Cardiac myocytes were exposed to hydrogen peroxide or a xanthine/xanthine oxidase system resulting in injury-induced release of lactate dehydrogenase. Bucillamine (125-500 microM) prevented lactate dehydrogenase release in a concentration-dependent manner. Bucillamine, which has two donatable thiol groups, was twice as protective as N-2-mercaptopropionyl glycine, which contains a single donatable thiol group. Dogs were then exposed to 90 min of coronary artery occlusion and 48 h of reperfusion before sacrifice. Beginning at the onset of reperfusion, bucillamine, 11 or 22 mg/kg per hour, or vehicle (saline) was administered intravenously for 3 h. There was a dose-related response to bucillamine for infarct size, normalized for size of the region at risk and adjusted for collateral blood flow to the ischemic region. Infarct size was reduced by 41% in the group treated with bucillamine 22 mg/kg per hour, compared with the vehicle group. Bucillamine, probably through an antioxidant mechanism, reduced infarct size when administered during reperfusion.
Horwitz
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LD
Division of Cardiology, Box B130, University of Colorado Health Sciences Center, 4200 E Ninth Avenue, Denver, CO 80262, U.S.A. lawrence.horwitz@uchsc.edu
Sherman
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NA
D000818:Animals; D002478:Cells, Cultured; D003097:Collateral Circulation / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D003545:Cysteine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D009203:Myocardial Infarction / Q000188:drug therapy / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D016037:Single-Blind Method; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000627:therapeutic use; D008625:Tiopronin / Q000737:chemistry / Q000627:therapeutic use
D013438:Sulfhydryl Compounds; D006861:Hydrogen Peroxide; D008625:Tiopronin; D007770:L-Lactate Dehydrogenase; D003545:Cysteine; C026535:bucillamine