title: Dexrazoxane Shows No Protective Effect in the Acute Phase of Reperfusion during Myocardial Infarction in Pigs.
abstract: Calcium and iron overload participate in the mechanisms of ischemia/reperfusion (I/R) injury during myocardial infarction (MI). Calcium overload induces cardiomyocyte death by hypercontraction, while iron catalyses generation of reactive oxygen species (ROS). We therefore hypothesized that dexrazoxane, an intracellular metal chelator, would attenuate I/R injury. MI was induced in pigs by occlusion of the left anterior descending artery for 1 hour followed by 2 hours reperfusion. Thirty minutes before reperfusion either 5 mg/ml dexrazoxane (n = 5) or saline (n = 5) was infused intravenously. Myocardial necrosis as percentage of the area at ischemic risk was found to be similar in both groups (77.2 ± 18% for dexrazoxane and 76.4 ± 14% for saline group) as determined by triphenyl tetrazolium chloride staining of the ischemic myocardium. Also, serum levels of troponin-I were similar in both groups. A conductance catheter was used to measure left ventricular pressure and volume at all times. Markers for tissue damage due to ROS (HNE), endothelial cell activation (CD31) and inflammation (IgG, C3b/c, C5b9, MCP-1) were assessed on tissue and/or in serum. No significant differences were observed between the groups for the parameters analyzed. To conclude, in this clinically relevant model of early reperfusion after acute myocardial ischemia, dexrazoxane lacked attenuating effects on I/R injury as shown by the measured parameters.
authors.affiliation: Department of Clinical Research, University of Bern, Bern, Switzerland.
authors.forename: Pranitha
authors.initials: P
authors.lastname: Kamat
authors.affiliation: ARTORG Center, University of Bern, Bern, Switzerland.
authors.forename: Stijn
authors.initials: S
authors.lastname: Vandenberghe
authors.affiliation: Department of Infectious Diseases, University of Bern, Bern, Switzerland.
authors.forename: Stephan
authors.initials: S
authors.lastname: Christen
authors.affiliation: Department of Clinical Research, University of Bern, Bern, Switzerland.
authors.forename: Anjan K
authors.initials: AK
authors.lastname: Bongoni
authors.affiliation: Department of Cardiology, Bern University Hospital, Bern, Switzerland.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Meier
authors.affiliation: Department of Clinical Research, University of Bern, Bern, Switzerland.
authors.forename: Robert
authors.initials: R
authors.lastname: Rieben
authors.affiliation: Department of Cardiology, Bern University Hospital, Bern, Switzerland.
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Khattab
mesh_terms: D000208:Acute Disease; D061605:Administration, Intravenous; D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism; D015932:Complement C3c / Q000378:metabolism; D015938:Complement Membrane Attack Complex / Q000378:metabolism; D064730:Dexrazoxane / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D009203:Myocardial Infarction / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology; D009336:Necrosis; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012307:Risk Factors; D013552:Swine; D019210:Troponin I / Q000097:blood; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D018932:Chemokine CCL2; D015938:Complement Membrane Attack Complex; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D017382:Reactive Oxygen Species; D019210:Troponin I; D064730:Dexrazoxane; D015932:Complement C3c