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Combined ADP and thromboxane A2 antagonism prevents cyclic flow variations in stenosed and endothelium-injured arteries in nonhuman primates. 1993

S K Yao, and J McNatt, and K Cui, and H V Anderson, and J P Maffrand, and L M Buja, and J T Willerson
Department of Internal Medicine, University of Texas Health Science Center at Houston.

BACKGROUND This study was designed to test the hypothesis that clopidogrel, a potent inhibitor of platelet aggregation, can eliminate cyclic flow variations in stenosed and endothelium-injured coronary and femoral arteries in nonhuman primates. RESULTS We studied five anesthetized, open-chest baboons. Blood flow velocity in the coronary and femoral arteries was monitored by pulsed Doppler flow probes placed around the arteries. Cyclic flow variations were established by mechanically injuring the endothelium of the arteries and by narrowing the arteries with external constrictors. Clopidogrel (10 to 20 mg/kg i.v. bolus plus 2.5 mg.kg-1 x h-1 continuous infusion) was administered 60 minutes after cyclic flow variations were established. Clopidogrel abolished cyclic flow variations in the coronary and femoral arteries of all five baboons (frequency of cyclic flow variations, 0/h versus 14/h at baseline, P < .001). Then epinephrine was infused (maximum average dose, 2.2 micrograms.kg-1 x min-1 i.v.). Epinephrine did not restore cyclic flow variations in the coronary or femoral arteries of any baboon. Before treatment with clopidogrel, ADP, collagen, and U46619, a thromboxane A2 mimetic, induced dose-dependent platelet aggregation in vitro. Serotonin, however, did not induce platelet aggregation in vitro. Clopidogrel given in vivo completely inhibited ADP-induced platelet aggregation and significantly diminished collagen- and U46619-induced platelet aggregation in vitro. CONCLUSIONS Clopidogrel eliminates cyclic flow variations in stenosed and endothelium-injured coronary and femoral arteries of nonhuman primates at least in part by antagonizing the platelet proaggregatory effects of ADP and thromboxane A2.

UI MeSH Term Description Entries
D010215 Papio A genus of the subfamily CERCOPITHECINAE, family CERCOPITHECIDAE, consisting of five named species: PAPIO URSINUS (chacma baboon), PAPIO CYNOCEPHALUS (yellow baboon), PAPIO PAPIO (western baboon), PAPIO ANUBIS (or olive baboon), and PAPIO HAMADRYAS (hamadryas baboon). Members of the Papio genus inhabit open woodland, savannahs, grassland, and rocky hill country. Some authors consider MANDRILLUS a subgenus of Papio. Baboons,Baboons, Savanna,Savanna Baboons,Baboon,Baboon, Savanna,Papios,Savanna Baboon
D010974 Platelet Aggregation The attachment of PLATELETS to one another. This clumping together can be induced by a number of agents (e.g., THROMBIN; COLLAGEN) and is part of the mechanism leading to the formation of a THROMBUS. Aggregation, Platelet
D012039 Regional Blood Flow The flow of BLOOD through or around an organ or region of the body. Blood Flow, Regional,Blood Flows, Regional,Flow, Regional Blood,Flows, Regional Blood,Regional Blood Flows
D003251 Constriction, Pathologic The condition of an anatomical structure's being constricted beyond normal dimensions. Stenosis,Stricture,Constriction, Pathological,Pathologic Constriction,Constrictions, Pathologic,Pathologic Constrictions,Pathological Constriction,Stenoses,Strictures
D003331 Coronary Vessels The veins and arteries of the HEART. Coronary Arteries,Sinus Node Artery,Coronary Veins,Arteries, Coronary,Arteries, Sinus Node,Artery, Coronary,Artery, Sinus Node,Coronary Artery,Coronary Vein,Coronary Vessel,Sinus Node Arteries,Vein, Coronary,Veins, Coronary,Vessel, Coronary,Vessels, Coronary
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D004730 Endothelium, Vascular Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components. Capillary Endothelium,Vascular Endothelium,Capillary Endotheliums,Endothelium, Capillary,Endotheliums, Capillary,Endotheliums, Vascular,Vascular Endotheliums
D005260 Female Females
D005263 Femoral Artery The main artery of the thigh, a continuation of the external iliac artery. Common Femoral Artery,Arteries, Common Femoral,Arteries, Femoral,Artery, Common Femoral,Artery, Femoral,Common Femoral Arteries,Femoral Arteries,Femoral Arteries, Common,Femoral Artery, Common
D006439 Hemodynamics The movement and the forces involved in the movement of the blood through the CARDIOVASCULAR SYSTEM. Hemodynamic

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