Enhanced endogenous thrombolysis induced by a specific factor Xa inhibitor, DX-9065a, evaluated in a rat arterial thrombolysis model in vivo.
We have previously established an animal model to investigate mechanisms of arterial thrombolysis in vivo and have demonstrated that endogenous thrombolysis, mediated by thrombin-activatable fibrinolysis inhibitor, is enhanced by administration of specific thrombin inhibitors. The aim of the present study was to evaluate the effects of a synthetic and specific factor Xa inhibitor, DX-9065a, on endogenous fibrinolysis. Mural thrombi were formed in rat mesenteric arterioles by helium-neon laser irradiation in the presence of Evans blue. Thrombolysis was continuously monitored by video microscopy and was quantified using image analysis software. Oral and intravenous administration of DX-9065a enhanced endogenous thrombolysis in vivo. The mechanisms require additional investigation using other experimental systems, but nevertheless, the present results extended our previous findings and further suggested that the enhanced fibrinolysis might be due to depressed activity thrombin-activatable fibrinolysis inhibitor. The synthetic factor Xa inhibitor could provide the basis for a useful thrombolytic agent.
Laboratory of Physiology, Faculty of Nutrition and High Technology Research Centre, Kobe Gakuin University, Nishi-ku, Kobe 651-2180, Japan. masaru_hashimoto@hotmail.com
Masaru
M
Hashimoto
Yuko
Y
Onobayashi
Kazuhiro
K
Oiwa
John C
JC
Giddings
Junichiro
J
Yamamoto
D000284:Administration, Oral; D000818:Animals; D001160:Arterioles; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D065427:Factor Xa Inhibitors; D005342:Fibrinolysis / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007091:Image Processing, Computer-Assisted; D007262:Infusions, Intravenous; D008297:Male; D008641:Mesenteric Vascular Occlusion / Q000188:drug therapy*; D018715:Microscopy, Video; D009281:Naphthalenes / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011422:Propionates / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D015912:Thrombolytic Therapy; D013927:Thrombosis / Q000188:drug therapy*
C086910:(2S)-2-(4-(((3S)-1-acetimidoyl-3-pyrrolidinyl)oxy)phenyl)-3-(7-amidino-2-naphtyl)propanoic acid; D004791:Enzyme Inhibitors; D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents; D009281:Naphthalenes; D011422:Propionates