Intravenous nitroglycerin infusion inhibits cyclic blood flow responses caused by periodic platelet thrombus formation in stenosed canine coronary arteries

Selatogrel, a potent and reversible antagonist of the P2Y12 receptor, inhibited FeCl3-induced thrombosis in rats. Here, we report the anti-thrombotic effect of selatogrel after subcutaneous applications in guinea pigs and mice. Selatogrel inhibited platelet function only 10 min after subcutaneous application in mice. In addition, in a modified Folts thrombosis model in guinea pigs, selatogrel prevented a decrease in blood-flow, indicative of the inhibition of ongoing thrombosis, approximately 10 min after subcutaneous injection. Selatogrel fully normalised blood flow; therefore, we speculate that it may not only prevent, but also dissolve, platelet thrombi. Thrombus dissolution was investigated using real-time intravital microscopy in mice. The infusion of selatogrel during ongoing platelet thrombus formation stopped growth and induced the dissolution of the preformed platelet thrombus. In addition, platelet-rich thrombi were given 30 min to consolidate in vivo. The infusion of selatogrel dissolved the preformed and consolidated platelet thrombi. Dissolution was limited to the disintegration of the occluding part of the platelet thrombi, leaving small mural platelet aggregates to seal the blood vessel. Therefore, our experiments uncovered a novel advantage of selatogrel: the dissolution of pre-formed thrombi without the disintegration of haemostatic seals, suggesting a bipartite benefit of the early application of selatogrel in patients with acute thrombosis.

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Measurement of the Platelet Response to Laserinduced Microvascular Injury

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647739 ◽

1974 ◽

Vol 32 (02/03) ◽

pp. 695-703 ◽

Cited By ~ 7

Author(s):

T Hovig ◽

F. N McKenzie ◽

K.-E Arfors

Keyword(s):

Blood Flow ◽

Internal Structure ◽

Blood Cells ◽

Thrombus Formation ◽

Platelet Response ◽

Microvascular Injury ◽

Ultrastructural Studies ◽

Laser Injury ◽

Complete Destruction ◽

Platelet Thrombus

SummaryMicrovascular injury was produced in rabbit mesentery and ear chamber preparations using a biolaser. Ultrastructural studies of the injury sites revealed damage to the endothelium which showed cytoplasmic swelling and flocculation. Complete destruction of the endothelium was not observed, indicating that sub endothelial structures were not exposed to blood flow. Microvascular thrombi which occurred at the sites of injury were composed of platelets which in general were loosely packed and showed minor alterations in shape and internal structure. Erythrocytes appeared to be heavily damaged by the laser injury. Fibrin was not observed. It is concluded that ADP may be released from red blood cells, and possibly from other sources, as a result of the laser injury, and that the platelet thrombus formation is induced by ADP.

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The Effect of Platelet PlA Polymorphism on Experimental Thrombus Formation in Man Depends on Blood Flow and Thrombogenic Substrate

Thrombosis and Haemostasis ◽

10.1055/s-0037-1615972 ◽

2001 ◽

Vol 85 (06) ◽

pp. 1097-1103 ◽

Cited By ~ 4

Author(s):

Kjell Sakariassen ◽

Hélène Grandjean ◽

Claire Thalamas ◽

Bernard Boneu ◽

Pierre Sié ◽

...

Keyword(s):

Blood Flow ◽

Ex Vivo ◽

Thrombus Formation ◽

Flow Properties ◽

Shear Rates ◽

Perfusion Chamber ◽

Platelet Receptor ◽

Platelet Deposition ◽

Coronary Syndromes ◽

Platelet Thrombus

SummaryA number of studies have reported conflicting data on the association of the PlA1/PlA2 polymorphism of the GPIIIa gene and coronary syndromes. We have investigated the effect of this polymorphism on experimental platelet thrombus formation in man. Forty healthy male volunteers were genotyped for the PlA1/PlA2 polymorphism. Thrombus formation was induced ex vivo by exposing a tissue factor (TF) or a collagencoated coverslip in a parallel plate perfusion chamber to native blood for 2 and 4 min. The shear rates at these surfaces were 650 and 2,600 s–1. Platelet and fibrin deposition was quantified by immunoenzymatic methods. The frequencies of PlA1/PlA1 and PlA1/PlA2 genotypes were 52.5% and 47.5%, respectively. Ex vivo deposition of fibrin on TF was not affected by the PlA1/PlA2 polymorphism. However, the ex vivo platelet deposition at 650 s–1 was higher in blood from PlA1/PlA1 individuals than in PlA1/PlA2 individuals (P = 0.008 at 4 min). On collagen, neither fibrin nor platelet deposition was significantly affected by the PlA1/PlA2 polymorphism. Platelet thrombus formation is significantly influenced by genetic variations in the GPIIIa platelet receptor. This effect depends on the blood flow properties and the nature of the thrombogenic stimulus.

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