Ro 44-9883, a New Non-Peptidic GPIIb-GPIIIa Antagonist Prevents Platelet Loss in a Guinea Pig Model of Extracorporeal Circulation

Jean-P Carteaux; Beat Steiner; Sébastien Roux

doi:10.1055/s-0038-1649676

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1993; 70(05): 817-821
DOI: 10.1055/s-0038-1649676

Platelets

Schattauer GmbH Stuttgart

Ro 44-9883, a New Non-Peptidic GPIIb-GPIIIa Antagonist Prevents Platelet Loss in a Guinea Pig Model of Extracorporeal Circulation

Jean-P Carteaux

The Pharma Division, Preclinical Research, Hoffmann-La Roche Ltd, Basel, Switzerland

,

Beat Steiner

The Pharma Division, Preclinical Research, Hoffmann-La Roche Ltd, Basel, Switzerland

,

Sébastien Roux

The Pharma Division, Preclinical Research, Hoffmann-La Roche Ltd, Basel, Switzerland

› Author Affiliations

Abstract

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Summary

Extensive contact between blood and artificial surfaces causes platelet activation and depletion. The aim of the present study was to test the efficacy of Ro 44-9883, a potent and selective peptidomimetic GPIIb-IIIa antagonist, in preventing platelet loss in guinea pigs undergoing extracorporeal circulation (ECC) with bubble oxygenation. In 15 guinea pigs, an arterio-arterial shunt was created and perfused for 1 h from the aortic arch to the descending aorta. The guinea pigs were divided into three groups: A control group receiving only heparin as an i.v. bolus, a low dose-treated group and a high dose-treated group receiving in addition to heparin and before starting ECC, 1 or 7 mg/kg Ro 449883 as an i.v. bolus, respectively. In the control group, the platelet count at 30 and 60 min of ECC was dramatically decreased (35 ± 4% and 25 ± 3% of initial value). In the low dose-treated group, Ro 44-9883 partially prevented the drop in platelet count (69 ± 8% and 54 ± 9%; p <0.05) whereas in the high dose-treated group, the platelet count was normal at 30 min (97 ± 8%) and only slightly decreased at 60 min (80 ± 7%). Mean arterial pressure and hematocrit were not significantly different between groups during the experiment. We conclude that i) ECC in guinea pigs provides an interesting in-vivo model for studying platelet loss by contact activation and ii) Ro 44-9883 prevents platelet loss during ECC in a dose dependent manner.

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References

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