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EXPERIMENTAL STUDY

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

José A. Barrabés, MD^*, David Garcia-Dorado, MD, FACC^*,*, Maribel Mirabet, PhD^*, Rosa-Maria Lidón, MD^*, Bernat Soriano, PharmD, Marisol Ruiz-Meana, PhD^*, Pilar Pizcueta, PhD, José Blanco, MD^*, Yolanda Puigfel, RN^* and Jordi Soler-Soler, MD, FACC^*

^* Servicios de Cardiología, Hospital Universitari Vall d’Hebron, Barcelona, Spain
Medicina Nuclear, Hospital Universitari Vall d’Hebron, Barcelona, Spain
Institut de Malalties Digestives, Hospital Clínic, Barcelona, Spain

Manuscript received December 20, 2000; revised manuscript received August 21, 2001, accepted October 11, 2001.

^* Reprint requests and correspondence: Dr. David Garcia-Dorado, Servicio de Cardiología, Hospital Universitari Vall d’Hebron, Pg. Vall d’Hebron 119-129, 08035 Barcelona, Spain.
dgdorado{at}hg.vhebron.es

OBJECTIVES: 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 µg/kg body weight and continuous infusion of 3 µg/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 (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 ^99mTc 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.

Abbreviations and Acronyms   ADP   adenosine diphosphate   CFR   cyclic flow reduction   CO   coronary occlusion   FBS   fetal bovine serum   GP   glycoprotein   HMPAO   hexamethylpropyleneamineoxime   LAD   left anterior descending coronary artery   MPO   myeloperoxidase   PBS   phosphate-buffered saline   PMNs   polymorphonuclear leukocytes   99mTc   technetium-99m

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