Experimental model of lower limb ischemia in rats and the effect of YM466, an oral direct factor Xa inhibitor.
A simple, quantitative, and reproducible model of lower limb ischemia was developed. Vascular injury was induced by ferric chloride (FeCl(3)) solution to the rat iliac artery, after which blood flow in all of the lower limbs were continuously monitored using a scanning laser Doppler blood flowmeter. After FeCl(3) injury, a distinct decrease in blood flow in the ischemic lower limb was observed and blood flow did not recover during the 30 min after vascular injury. YM466, an oral direct factor Xa inhibitor, dose-dependently inhibited the reduction of peripheral blood flow. The area under the blood flow-time curve during 30 min after vascular injury improved dose-dependently, with significance at doses of 3 and 10 mg/kg. These results suggest that factor Xa inhibitors are effective in patients with peripheral arterial disease, and that this vascular injury model is a useful tool for the screening and evaluation of the efficacy of new antithrombotic agents.
Iwatsuki
Yoshiyuki
Y
Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Ibaraki, Japan. yoshiyuki.iwatsuki@jp.astellas.com
Sakata
Chinatsu
C
Kawasaki
Tomihisa
T
Okada
Masamichi
M
D000284:Administration, Oral; D000818:Animals; D001808:Blood Vessels / Q000473:pathology; D002712:Chlorides; D004305:Dose-Response Relationship, Drug; D065427:Factor Xa Inhibitors; D005290:Ferric Compounds / Q000633:toxicity; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007511:Ischemia / Q000188:drug therapy* / Q000473:pathology; D035002:Lower Extremity / Q000098:blood supply* / Q000473:pathology; D008297:Male; D009281:Naphthalenes / Q000008:administration & dosage / Q000627:therapeutic use*; D010880:Piperidines / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects
D002712:Chlorides; D065427:Factor Xa Inhibitors; D005290:Ferric Compounds; D005343:Fibrinolytic Agents; D009281:Naphthalenes; D010880:Piperidines; C111032:YM 60828; C024555:ferric chloride