Effects of vapiprost, a novel thromboxane receptor antagonist, on thrombus formation and vascular patency after thrombolysis by tissue‐type plasminogen activator

Abstract

A thrombus was induced in the rat femoral artery by endothelial damage due to the photochemical reaction between systemically‐injected Rose Bengal and transillumination with green light (wavelength: 540 nm). The artery of the control rat was completely occluded in 302.8 ± 27.0 s after the initiation of the reaction. Pretreatment with vapiprost (0.1, 0.3 and 1.0 mg kg−1, i.v., 5 min before the reaction) prolonged the time required to occlude the femoral artery in a dose‐dependent manner. The efficacy of vapiprost on the time required for occlusion was over 10 times higher than that of aspirin which was administered 30 min before the reaction. The thrombolytic effects of tissue‐type plasminogen activator (tPA) on the established arterial thrombus in the presence and absence of vapiprost were also studied in the same model. When vapiprost (0.3 mg kg−1, i.v.) was administered just before tPA infusion (100 μg kg−1 min−1 for 30 min), the time required to reperfuse the occluded artery was reduced, the incidence of the reperfusion was increased and the arterial blood flow after reperfusion was improved. When vapiprost (1.0 mg kg−1 daily p.o.) was administered for 1 week after the establishment of reperfusion by tPA combined with vapiprost, the patency of the reperfused artery was improved and the femoral arterial blood flow was better preserved than after treatment with only tPA. These findings suggest that this thromboxane receptor antagonist may be a useful adjunct to anti‐thrombotic therapy. The combination therapy with tPA may be more effective than treatment with tPA alone and provides greater protection against reocculsion after reperfusion.

Evaluation of the combination of a tissue-type plasminogen activator, SUN9216, and a thromboxane A2 receptor antagonist, vapiprost, in a rat middle cerebral artery thrombosis model.

“…7 The combination of green light and rose bengal did not damage smooth muscle in the tunica media and lamina elastica interna of rat femoral arteries in a transmission electron microscopic study. 19 It is unclear whether this combination affects polymorphonuclear leukocyte function. Recently, thrombolytic therapy has been performed in patients within several hours of acute cerebral thrombosis and has been demonstrated to be effective without severe intracerebral hemorrhage.…”

Characterization of a novel thrombotic middle cerebral artery occlusion model in monkeys that exhibits progressive hypoperfusion and robust cortical infarction

“…In this model, reactive oxygen species cause endothelial injury followed by the adhesion and aggregation of platelets to fibrin nets, and subsequent formation of a platelet-and fibrinrich thrombus at the irradiated site (Dietrich et al, 1987;Matsuno et al, 1992;Umemura et al, 1993;Watson et al, 1985). In the present study, we have modified the intensity and duration of photoirradiation to produce a defined thrombotic occlusion of the MCA Watson et al, 1985).…”

Inhibitory Effect of Clopidogrel, Vapiprost and Argatroban on the Middle Cerebral Artery Thrombosis in the Rat

“…However, vapiprost, TXA2-receptor antagonist, inhibited platelet agrregation induced by collagen in whole blood (22) and was effective in the MCA thrombosis model. This suggests that TXA2 may be involved in the thrombogenesis of the MCA in this model.…”