title: Catalytic peroxynitrite decomposition improves reperfusion injury after heart transplantation.
abstract: OBJECTIVE
  Peroxynitrite, a reactive nitrogen species, has been implicated in the development of ischemia-reperfusion injury. The present study investigated the effects of the potent peroxynitrite decomposition catalyst FP15 on myocardial and endothelial function after hypothermic ischemia-reperfusion in a heterotopic rat heart transplantation model.
  
  
  METHODS
  After a 1-hour ischemic preservation and implantation of donor hearts, reperfusion was started after application of vehicle (5% glucose solution) or FP15 (0.3 mg/kg). The assessment of left ventricular pressure-volume relations, total coronary blood flow, endothelial function, immunohistochemical markers of nitro-oxidative stress, and myocardial high-energy phosphates was performed at 1 and 24 hours of reperfusion.
  
  
  RESULTS
  After 1 hour of reperfusion, myocardial contractility (maximal slope of systolic pressure increment at 140 μL left ventricular volume: 5435 ± 508 mm Hg/s vs 2346 ± 263 mm Hg/s), coronary blood flow (3.98 ± 0.33 mL/min/g vs 2.74 ± 0.29 mL/min/g), and endothelial function were significantly improved, nitro-oxidative stress was reduced, and myocardial high-energy phosphate content was preserved in the FP15-treated animals compared with controls.
  
  
  CONCLUSIONS
  Pharmacologic peroxynitrite decomposition reduces reperfusion injury after heart transplantation as the result of reduction of nitro-oxidative stress and prevention of energy depletion and exerts a beneficial effect against reperfusion-induced graft cardiac and coronary endothelial dysfunction.
authors.affiliation: Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany. gabor.szabo@urz.uni-heidelberg.de
authors.forename: Gábor
authors.initials: G
authors.lastname: Szabó
authors.forename: Sivakkanan
authors.initials: S
authors.lastname: Loganathan
authors.forename: Béla
authors.initials: B
authors.lastname: Merkely
authors.forename: John T
authors.initials: JT
authors.lastname: Groves
authors.forename: Matthias
authors.initials: M
authors.lastname: Karck
authors.forename: Csaba
authors.initials: C
authors.lastname: Szabó
authors.forename: Tamás
authors.initials: T
authors.lastname: Radovits
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003326:Coronary Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D004734:Energy Metabolism / Q000187:drug effects; D016027:Heart Transplantation / Q000009:adverse effects*; D007150:Immunohistochemistry; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology*; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D030421:Peroxynitrous Acid / Q000378:metabolism*; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects
chemical_list: D015415:Biomarkers; C471469:FeCl tetrakis-2-(triethyleneglycolmonomethylether)pyridylporphyrin; D008665:Metalloporphyrins; D030421:Peroxynitrous Acid; D011064:Poly Adenosine Diphosphate Ribose; C002744:3-nitrotyrosine; D000249:Adenosine Monophosphate; D014443:Tyrosine; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate