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BMC Cardiovasc Disord ; 2: 10, 2002 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-12086588

RESUMO

BACKGROUND: GPIIb/IIIa inhibitors abciximab and eptifibatide have been shown to inhibit platelet aggregation in ischemic heart disease. Our aim was to test the efficacy of abiciximab (Reo Pro) or eptifibatide (Integrilin) alone or in combination with plasminogen activator (t-PA) in an experimental model of ischemia reperfusion (I/R) in hamster cheek pouch microcirculation visualized by fluorescence microscopy. Hamsters were treated with saline, or abiciximab or eptifibatide or these drugs combined with t-PA infused intravenously 10 minutes before ischemia and through reperfusion. We measured the microvessel diameter changes, the arteriolar red blood cell (RBC) velocity, the increase in permeability, the perfused capillary length (PCL), and the platelet and leukocyte adhesion on microvessels. RESULTS: I/R elicited large increases in the platelet and leukocyte adhesion and a decrease in microvascular perfusion. These responses were significantly attenuated by abiciximab or eptifibatide (PCL:70 and 65% at 5-10 mins of reperfusion and 85 and 87% at 30 mins of reperfusion, respectively, p < 0.001) while t-PA combined with abiciximab or eptifibatide, was more effective and microvascular perfusion recovered immediately after postischemic reperfusion. CONCLUSIONS: Platelets are crucial in I/R injury, as shown by the treatment with abicixmab or eptifibatide, which decreased platelet aggregation in microvessels, and also decreased leukocyte adhesion in venules. Arterial vasoconstriction, decreased arterial RBC velocity and alterations in the endothelial barrier with increased permeability delayed the complete restoration of blood flow, while t-PA combined with inhibition of platelet aggregation speeded up the capillary perfusion after reperfusion.


Assuntos
Anticorpos Monoclonais/farmacologia , Fragmentos Fab das Imunoglobulinas/farmacologia , Leucócitos/efeitos dos fármacos , Peptídeos/farmacologia , Ativadores de Plasminogênio/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Traumatismo por Reperfusão/tratamento farmacológico , Abciximab , Animais , Arteríolas/efeitos dos fármacos , Arteríolas/fisiopatologia , Capilares/efeitos dos fármacos , Capilares/fisiopatologia , Bochecha , Cricetinae , Avaliação Pré-Clínica de Medicamentos , Quimioterapia Combinada , Eptifibatida , Microcirculação/efeitos dos fármacos , Microcirculação/fisiologia , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Traumatismo por Reperfusão/fisiopatologia , Vênulas/efeitos dos fármacos , Vênulas/fisiopatologia
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