Comparison of Antithrombotic Activity of Heparin, ASA, Sulfinpyrazone and VK 744 in a Rat Model of Arterial Thrombosis

1978 ◽  
Vol 7 (5) ◽  
pp. 282-293 ◽  
Author(s):  
R.B. Philp ◽  
I. Francey ◽  
B.A. Warren
Keyword(s):  
Rat Model ◽  
Arterial Thrombosis ◽  
Antithrombotic Activity

Comparative Studies of an Orally-active Factor Xa Inhibitor, YM-60828, with other Antithrombotic Agents in a Rat Model of Arterial Thrombosis

1998 ◽  
Vol 79 (02) ◽  
pp. 410-416 ◽  
Author(s):  
Kazuo Sato ◽  
Yumiko Sakai ◽  
Fukushi Hirayama ◽  
Hiroyuki Koshio ◽  
Yuta Taniuchi ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Arterial Thrombosis ◽  
Thrombus Formation ◽  
Factor Xa ◽  
Test Drug ◽  
Antithrombotic Agent ◽  
Antithrombotic Activity ◽  
Thrombosis Model ◽  
Treatment And Prevention ◽  
Orally Active

SummaryWe examined the antithrombotic activity of a novel synthetic inhibitor of factor Xa, YM-60828, in an electrically-induced carotid artery thrombosis model in rats. In the first experiment, the antithrombotic activity of YM-60828 after i.v. infusion was compared with those of heparin, darteparin and argatroban. Test drug was administered by i.v. infusion from 30 min before electrical stimulation to the end of the experiment. YM-60828 at 1 mg/kg/h significantly improved patency status, prolonged the time to occlusive thrombus formation and duration of patency. Heparin at 300 U/kg/h also improved these parameters, but were accompanied by a marked increase in systemic coagulation time. In the second experiment, the antithrombotic activity of YM-60828 after oral administration was compared with those of ticlopidine, cilostazol, aspirin, beraprost, ethyl icosapentate and warfarin. Test drug was orally administered to fasted rats 60 min before electrical stimulation. YM-60828 at 30 mg/kg p.o., but not ticlopidine, cilostazol, aspirin, beraprost, ethyl icosapentate or warfarin, significantly reduced the incidence of occlusion and improved carotid arterial patency. These results suggest that YM-60828 may be a promising antithrombotic agent for the treatment and prevention of arterial thrombosis which can be given by oral as well as intravenous administration.

scholarly journals Mumefural Improves Blood Flow in a Rat Model of FeCl3-Induced Arterial Thrombosis

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3795
Author(s):  
Jihye Bang ◽  
Won Kyung Jeon
Keyword(s):  
Blood Flow ◽  
Blood Vessels ◽  
Rat Model ◽  
Arterial Thrombosis ◽  
Thrombus Formation ◽  
Sprague Dawley ◽  
Fiber Damage ◽  
Sprague Dawley Rats ◽  
Related Proteins

Mumefural (MF), a bioactive component of the processed fruit of Prunus mume Sieb. et Zucc, is known to inhibit platelet aggregation induced by agonists in vitro. In this study, we investigated the anti-thrombotic effects of MF using a rat model of FeCl3-induced arterial thrombosis. Sprague–Dawley rats were intraperitoneally injected with MF (0.1, 1, or 10 mg/kg) 30 min before 35% FeCl3 treatment to measure the time to occlusion using a laser Doppler flowmeter and to assess the weight of the blood vessels containing thrombus. MF treatment significantly improved blood flow by inhibiting occlusion and thrombus formation. MF also prevented collagen fiber damage in injured vessels and inhibited the expression of the platelet activation-related proteins P-selectin and E-selectin. Moreover, MF significantly reduced the increased inflammatory signal of nuclear factor (NF)-κB, toll-like receptor 4 (TLR4), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 in blood vessels. After administration, MF was detected in the plasma samples of rats with a bioavailability of 36.95%. Therefore, we suggest that MF may improve blood flow as a candidate component in dietary supplements for improving blood flow and preventing blood circulation disorders.

Rat model of arterial thrombosis induced by ferric chloride

1990 ◽  
Vol 60 (4) ◽  
pp. 269-280 ◽  
Author(s):  
K.D. Kurz ◽  
B.W. Main ◽  
G.E. Sandusky
Keyword(s):  
Ferric Chloride ◽  
Rat Model ◽  
Arterial Thrombosis

Abstract 1718: Combination of Direct Acting FXa Inhibitor and P2Y 12 Antagonist at Non-Effective doses Provides Significant Inhibition of Arterial Thrombosis

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Patrick Andre ◽  
Pamela B Conley ◽  
Francis Deguzman ◽  
Yvonne Pak ◽  
Mayuko Inagaki ◽  
...  
Keyword(s):  
Arterial Thrombosis ◽  
Plasma Concentrations ◽  
Chronic Phase ◽  
Vascular Occlusion ◽  
Mesenteric Arteries ◽  
Late Time ◽  
Thrombotic Risk ◽  
Antithrombotic Activity ◽  
Effective Doses ◽  
Fxa Inhibitor

Previous studies have shown that inhibition of FXa and P2Y 12 used individually inhibit arterial thrombosis. The present study was designed to determine the antithrombotic activity achieved by the combination of non-effective doses of PRT054021 (FXa inhibitor) and PRT060128 (P2Y 12 antagonist). Arterial thrombosis was achieved by FeCl 3 injury of mesenteric arteries of the mouse and monitored in real time using intravital microscopy. Antagonism of either FXa or P2Y 12 dose-dependently inhibited early (time for appearance of first thrombus, TFFT) and late (time to vascular occlusion, TTO) phases of thrombosis (see Table ). Maximal effects were achieved at plasma concentrations superior or equal to 1 μg/ml for the two antagonists. Interestingly, the co-administration of non-effective doses of PRT054021 and PRT060128 significantly delayed time for appearance of first thrombus and vascular occlusion, demonstrating potent synergistic antithrombotic activity. PRT054021 and PRT060128 demonstrated a strong synergistic effect when administered in combination at non-effective doses. This combination is of particular relevance in acute settings, when thrombotic risk is at its paroxysm and maximal protection is sought as early as possible. These data also indicate that combined inhibition of FXa and P2Y 12 by reversible antagonists could provide substantial benefits to ACS patients throughout the chronic phase of the disease.

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