title: Lack of effect of glycoprotein IIb/IIIa blockade on myocardial platelet or polymorphonuclear leukocyte accumulation and on infarct size after transient coronary occlusion in pigs.
abstract: OBJECTIVE
  We sought to assess the effect of glycoprotein (GP) IIb/IIIa blockade on myocardial platelet and polymorphonuclear leukocyte accumulation and on infarct size after coronary injury and transient coronary occlusion (CO) in pigs.
  
  
  BACKGROUND
  It has been suggested that platelet GP IIb/IIIa blockade might reduce the severity of microvascular damage after reperfusion.
  
  
  METHODS
  Sixteen thiopental-anesthetized, open-chest pigs, in whom platelets had been labeled with technetium-99m (99mTc) on the previous day, were submitted to catheter-induced left anterior descending coronary artery (LAD) injury followed by 55 min of CO and 5 h of reperfusion. Five minutes before reflow, the animals were blindly allocated to receive lamifiban (intravenous bolus of 250 microg/kg body weight and continuous infusion of 3 microg/kg per min) or saline.
  
  
  RESULTS
  Lamifiban had a rapid and potent platelet anti-aggregatory effect, as demonstrated by significant prolongation of the bleeding time and profound (approximately 90%) inhibition of ex vivo platelet aggregation, and completely prevented the development of cyclic flow reductions of the LAD (0 vs. 5 +/- 1, one of them followed by re-occlusion, in control animals, p = 0.005). However, compared with animals receiving placebo, those treated with lamifiban had a similar (p = NS) content of (99m)Tc platelets in the reperfused myocardium (288 +/- 40% vs. 205 +/- 27% of the value in the control region, respectively) and similar myeloperoxidase activity (0.50 +/- 0.17 U/g vs. 0.47 +/- 0.17 U/g, respectively) and infarct size (46.8 +/- 12.0% vs. 49.8 +/- 10.5% of the area at risk, respectively). Arteriolar platelet thromboemboli were very rarely seen on histologic analysis. Lamifiban did not modify platelet P-selectin expression in additional studies.
  
  
  CONCLUSIONS
  Platelet GP IIb/IIIa blockade has a potent antithrombotic effect at the culprit lesion, but does not significantly reduce the magnitude of microvascular platelet accumulation or myocardial damage after transient CO.
authors.affiliation: Servicio de Cardiología, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Barrabés
authors.forename: David
authors.initials: D
authors.lastname: Garcia-Dorado
authors.forename: Maribel
authors.initials: M
authors.lastname: Mirabet
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Lidón
authors.forename: Bernat
authors.initials: B
authors.lastname: Soriano
authors.forename: Marisol
authors.initials: M
authors.lastname: Ruiz-Meana
authors.forename: Pilar
authors.initials: P
authors.lastname: Pizcueta
authors.forename: José
authors.initials: J
authors.lastname: Blanco
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Puigfel
authors.forename: Jordi
authors.initials: J
authors.lastname: Soler-Soler
mesh_terms: D000085:Acetates / Q000494:pharmacology*; D000818:Animals; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D015425:Myocardial Reperfusion; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013552:Swine; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: D000085:Acetates; D010975:Platelet Aggregation Inhibitors; D014443:Tyrosine; C084062:lamifiban; D009195:Peroxidase