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.
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.
Barrabés
José A
JA
Servicio de Cardiología, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
Garcia-Dorado
David
D
Mirabet
Maribel
M
Lidón
Rosa Maria
RM
Soriano
Bernat
B
Ruiz-Meana
Marisol
M
Pizcueta
Pilar
P
Blanco
José
J
Puigfel
Yolanda
Y
Soler-Soler
Jordi
J
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*
D000085:Acetates; D010975:Platelet Aggregation Inhibitors; D014443:Tyrosine; C084062:lamifiban; D009195:Peroxidase