title: Controlled reperfusion with intravenous bivalirudin and intracoronary abciximab combination therapy in the porcine myocardial infarction model.
abstract: BACKGROUND
  The reperfusion injury (RI) remains a significant limitation of primary PCI, therefore we evaluated the role of intracoronary abciximab and bivalirudin for anticoagulation on myocardial salvage and RI in the porcine model of ischemia/reperfusion.
  
  
  METHODS
  Myocardial infarction was induced in 23 pigs by 60-minute over-the-wire (OTW) balloon occlusion of the LAD. Animals received intravenous bivalirudin and then five minutes prior to reperfusion, either a coronary downstream infusion of abciximab (n=11) or saline (n=12) through the central lumen of an OTW catheter. All animals were followed for 48 hours.
  
  
  RESULTS
  Histological analysis showed that infarct area (IA) and area at risk (AAR) were comparable between groups (IA/AAR%: 57.6 ± 8% vs. 57.1 ± 7%, p=0.8). Confirming this trend, biochemical markers (troponin I, TNF-alpha, IL-6, hsCRP, adiponectin, and VCAM) and left ventricular ejection fraction were also similar at 48 hours. Adhesion markers like ICAM and P-selectin were significantly decreased in the study group, nevertheless histological evidence of leukocyte extravasation was similar. The enhancement of apoptosis by TUNEL was comparable in both groups. The number of hemorrhagic infarctions confirmed by micro and macroscopic evaluation tended to be higher in the study group (70% vs. 20%, p=0.07).
  
  
  CONCLUSIONS
  Despite lowered concentrations of adhesion molecules, intracoronary abciximab with peripheral bivalirudin is not superior to bivalirudin unaided in terms of myocardial salvage caused by RI in the porcine ischemia/reperfusion model. This might be due to local hemorrhage caused by abciximab.
authors.affiliation: Center for Cardiovascular Research and Development, American Heart of Poland, Katowice, Poland. pbuszman@gmail.com
authors.forename: Piotr P
authors.initials: PP
authors.lastname: Buszman
authors.forename: Wojciech
authors.initials: W
authors.lastname: Wojakowski
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Milewski
authors.forename: Marcin
authors.initials: M
authors.lastname: Dębiński
authors.forename: Jacek
authors.initials: J
authors.lastname: Pająk
authors.forename: Michael S
authors.initials: MS
authors.lastname: Aboodi
authors.forename: Wanda
authors.initials: W
authors.lastname: Jackiewicz
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kawka
authors.forename: Andrzej
authors.initials: A
authors.lastname: Bochenek
authors.forename: Jayne
authors.initials: J
authors.lastname: Prats
authors.forename: Juan F
authors.initials: JF
authors.lastname: Granada
authors.forename: Greg L
authors.initials: GL
authors.lastname: Kałuża
authors.forename: Pawel E
authors.initials: PE
authors.lastname: Buszman
mesh_terms: D000077284:Abciximab; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use*; D023201:CD40 Ligand / Q000276:immunology; D004338:Drug Combinations; D005260:Female; D006629:Hirudins / Q000008:administration & dosage; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage / Q000627:therapeutic use*; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D015425:Myocardial Reperfusion / Q000379:methods; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D013552:Swine; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000925:Anticoagulants; D004338:Drug Combinations; D006629:Hirudins; D007140:Immunoglobulin Fab Fragments; D010446:Peptide Fragments; D011994:Recombinant Proteins; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D023201:CD40 Ligand; C074619:bivalirudin; D000077284:Abciximab