Antithrombotic Activity of NSP-513, a Novel Selective Phosphodiesterase 3 Inhibitor, on Femoral Arterial Thrombosis Induced by Physical Stenosis and Electrical Current: Comparison of Antithrombotic and Hemodynamic Effects

2000 ◽  
Vol 35 (4) ◽  
pp. 586-594 ◽  
Author(s):  
Hiroyasu Hirose ◽  
Satoshi Mashiko ◽  
Toshifumi Kimura ◽  
Fumiaki Ishida ◽  
Nobuo Mochizuki ◽  
...  
Keyword(s):  
Arterial Thrombosis ◽  
Electrical Current ◽  
Hemodynamic Effects ◽  
Antithrombotic Activity ◽  
Phosphodiesterase 3

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.

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.

The influence of the new hypoglycemic agent Limiglidol on the parameters of hemostasis in experimental diabetes mellitus

2015 ◽  
Vol 61 (1) ◽  
pp. 51-56 ◽  
Author(s):  
A F Kucherenko ◽  
A A Spasov ◽  
L V Naumenko
Keyword(s):  
Platelet Aggregation ◽  
Blood Viscosity ◽  
Arterial Thrombosis ◽  
Experimental Diabetes ◽  
Thrombus Formation ◽  
Electrical Current ◽  
Experimental Diabetes Mellitus ◽  
Shear Rates ◽  
Hypoglycemic Agent ◽  
Flow Through

Platelet aggregation was assessed by the method of G. Born modified as described by Z.A. Gabbasov. Blood viscosity was measured using an AKR-2 rotating-type viscometer - rheological blood analyzer at six shear rates (10 s-1, 20 s-1, 50 s-1, 100 s-1, 200 s-1, and 300 s-1) simulating different intensities of the blood flow through the vessels. The model of arterial thrombosis induced by electrical current was constructed based on the method of G. Guglielmi et al (1991). Gliclazide was used in the studies of Limiglidol antiaggregant and antithrombotic properties and pentoxifylline in the studies of the influence of Limiglidol on rheological blood properties. It was shown that Limiglidol inhibited platelet aggregation and prolonged the time of thrombus formation. It proved to be superior to gliclazide in terms of these activities and reduced blood viscosity to a higher degree than pentoxifylline.

scholarly journals Thrombomodulin is required for the antithrombotic activity of thrombin mutant W215A/E217A in a mouse model of arterial thrombosis

2012 ◽  
Vol 130 (4) ◽  
pp. 646-648 ◽  
Author(s):  
Cristina P. Vicente ◽  
Hartmut Weiler ◽  
Enrico Di Cera ◽  
Douglas M. Tollefsen
Keyword(s):  
Mouse Model ◽  
Arterial Thrombosis ◽  
Antithrombotic Activity

Study of a new benzimidazole derivative having in its structure a sterically hindered phenolic substituent on models of arterial and venous thrombosis

2020 ◽  
Author(s):  
А.А. Спасов ◽  
А.Ф. Кучерявенко ◽  
К.А. Гайдукова ◽  
В.С. Сиротенко ◽  
О.Н. Жуковская
Keyword(s):  
Venous Thrombosis ◽  
Arterial Thrombosis ◽  
Benzimidazole Derivative ◽  
Vena Cava ◽  
Male Rats ◽  
Control Group ◽  
Vena Cava Inferior ◽  
Antithrombotic Activity ◽  
Thrombosis Model ◽  
Venous Thromboses

Введение: Тромбоциты являются ключевыми медиаторами патогенеза артериальных тромбозов и атеросклероза. Поэтому изучение антиагрегантных средств на предмет антитромботической активности на различных моделях артериальных и венозных тромбозов является актуальным. Цель исследования: изучение антитромботической активности соединения РУ-1144 (производного бензимидазола) в сравнении с ацетилсалициловой кислотой (АСК) и клопидогрелом на моделях артериального и венозного тромбозов. Материалы и методы: Артериальный тромбоз моделировали на сонной артерии крыс-самцов аппликацией постоянного электрического тока. Воздействие на сосуд выполняли до момента полной окклюзии, регистрируемой на мониторе доплерографа. Венозной тромбоз моделировали на крысах-самцах полной перевязкой нижней полой вены на 24 ч; через сутки проводили изъятие тромба из сосуда и его взвешивание. В экспериментальных группах животным внутрижелудочно вводили соединение РУ-1144 и препараты сравнения — АСК и клопидогрел, в контрольной группе животным внутрижелудочно вводили дистиллированную воду. Для подтверждения отсутствия влияния хирургических манипуляций на организм животного в исследование модели венозного тромбоза была включена группа ложнооперированных крыс. Результаты: На модели артериального тромбоза установлена более высокая антитромботическая активность соединения РУ-1144 по сравнению с АСК и клопидогрелом в 2,5 и 7,4 раза соответственно. В модели венозного тромбоза соединение РУ-1144 уменьшало среднюю массу венозных тромбов в 5,3 раза по сравнению с группой контроля и превосходило по антитромботической активности АСК и клопидогрел в 3,5 и 1,9 раза. Заключение: Соединение РУ-1144 способно предотвращать патологические процессы, связанные с тромбообразованием, не только в сонной артерии, но и в нижней полой вене. Background: Platelets are key mediators of the pathogenesis of arterial thrombosis and atherosclerosis. So, that is actual to study antithrombotic activity of antiplatelet agents in various models of arterial and venous thromboses. Objectives: to study the antithrombotic activity of RU-1144 compound (benzimidazole derivative) as compared with acetylsalicylic acid (ASA) and clopidogrel on models of arterial and venous thromboses. Materials/Methods: Arterial thrombosis was modeled on the carotid artery of male rats by application of direct electric current. Exposure was performed until full vessel occlusion recorded by Dopplerograf. Venous thrombosis was modeled on male rats by complete ligation of vena cava inferior for 24 hours; a day later the thrombus was removed from the vessel and weighed. In the experimental groups the animals were injected intragastrically with the compound RU-1144 and the comparison drugs — ASA and clopidogrel; in the control group the animals were administered distilled water intragastrically. To confirm the absence of the effect of surgical manipulations on the animal’s organism, a group of false-operated rats was included in the study of venous thrombosis model. Results: In arterial thrombosis model RU-1144 compound had a higher antithrombotic activity as compared with ASA and clopidogrel by 2.5 and 7.4 times, respectively. In venous thrombosis model RU-1144 compound reduced the average weight of venous clots by 5.3 times as compared with the control group and exceeded antithrombotic activity of ASA and clopidogrel by 3.5 and 1.9 times. Conclusions: RU-1144 compound capable to prevent the pathological processes associated with thrombus formation in carotid artery as well as in vena cava inferior.

Sign in / Sign up

Export Citation Format

Share Document