Effects of vapiprost, a novel thromboxane receptor antagonist, on thrombus formation and vascular patency after thrombolysis by tissue-type plasminogen activator.
1. 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. 2. 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. 3. 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 micrograms 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. 4. 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. 5. 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 reocclusion after reperfusion.
Matsuno
H
H
Department of Pharmacology, Hamamatsu University, School of Medicine, Japan.
Uematsu
T
T
Umemura
K
K
Takiguchi
Y
Y
Wada
K
K
Nakashima
M
M
D000818:Animals; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D007275:Injections, Intravenous; D008297:Male; D008854:Microscopy, Electron; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors*; D017482:Receptors, Thromboxane; D013927:Thrombosis / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000494:pharmacology; D014654:Vascular Patency / Q000187:drug effects*
D001713:Biphenyl Compounds; D006538:Heptanoic Acids; D010975:Platelet Aggregation Inhibitors; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D010959:Tissue Plasminogen Activator; C060013:vapiprost; D001241:Aspirin