Controlled reperfusion with intravenous bivalirudin and intracoronary abciximab combination therapy in the porcine myocardial infarction model

Thromb Res. 2012 Aug;130(2):265-72. doi: 10.1016/j.thromres.2011.10.020. Epub 2011 Nov 12.

Abstract

Introduction: 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.

Materials and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abciximab
  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / therapeutic use*
  • Anticoagulants / administration & dosage
  • Anticoagulants / therapeutic use*
  • CD40 Ligand / immunology
  • Drug Combinations
  • Female
  • Hirudins / administration & dosage
  • Immunoglobulin Fab Fragments / administration & dosage
  • Immunoglobulin Fab Fragments / therapeutic use*
  • Intercellular Adhesion Molecule-1 / immunology
  • Male
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / immunology
  • Myocardial Infarction / pathology
  • Myocardial Reperfusion Injury / drug therapy*
  • Myocardial Reperfusion Injury / immunology
  • Myocardial Reperfusion Injury / pathology
  • Myocardial Reperfusion* / methods
  • Myocardium / pathology
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / therapeutic use*
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / therapeutic use
  • Swine
  • Vascular Cell Adhesion Molecule-1 / immunology

Substances

  • Antibodies, Monoclonal
  • Anticoagulants
  • Drug Combinations
  • Hirudins
  • Immunoglobulin Fab Fragments
  • Peptide Fragments
  • Recombinant Proteins
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • CD40 Ligand
  • bivalirudin
  • Abciximab