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Antithrombin and thrombolytic effects of a new antithrombin agent: angioscopic and angiographic comparison with
T Tomaru1, F Nakamura, A Y Miwa
1Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Insights
Argatroban and batroxobin effectively reduced thrombus size and prevented formation in canine arteries. Heparin showed no significant effect, highlighting argatroban and batroxobin as potent antithrombotic agents.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Thrombosis Biology
Background:
- Thrombosis poses a significant risk for cardiovascular events.
- Evaluating novel antithrombotic agents is crucial for improving patient outcomes.
- Understanding the comparative efficacy of different antithrombotic mechanisms is essential.
Purpose of the Study:
- To compare the antithrombotic effects of argatroban, heparin, and batroxobin in canine models.
- To assess both the thrombus size reduction and preventive effects of these agents.
- To investigate the impact on activated partial thromboplastin time (APTT) and fibrinogen levels.
Main Methods:
- Canine coronary and iliac arteries were used to model occlusive thrombus formation via balloon injury.
- Intravenous infusion of argatroban, heparin, or batroxobin was administered one hour post-thrombus induction.
- Angioscopy and angiography were employed to quantify thrombus size and arterial stenosis before and after treatment.
Main Results:
- Argatroban and batroxobin significantly reduced thrombus area in both iliac and coronary arteries, unlike heparin.
- Argatroban demonstrated superior thrombus size reduction compared to heparin and batroxobin in angiography.
- Argatroban and heparin markedly prolonged APTT, while batroxobin significantly reduced fibrinogen levels.
Conclusions:
- Both antithrombin (argatroban) and defibrinogenating (batroxobin) agents exhibit significant antithrombotic efficacy.
- These agents effectively prevent thrombus formation and reduce existing thrombus size without excessive APTT prolongation.
- Argatroban and batroxobin represent promising therapeutic options for managing thrombotic conditions.
Abstract:
The antithrombotic effect of three different types of antithrombotic agents (antithrombin:argatroban, heparin, defibrinogenating agent:batroxobin) were evaluated in canine coronary and iliac arteries. An occlusive thrombus was produced by balloon injury. One of the three agents was infused intravenously at 1 hour after thrombus formation (heparin 250 U/kg, argatroban 0.5 mg/kg, batroxobin 0.5 U/kg) and the effect of thrombus size reduction was evaluated. On the contralateral side of the iliac artery, the preventive effect of these agents on thrombus formation was evaluated after balloon injury. In the iliac artery, angioscopic percent area obstruction by the thrombus before and 60 minutes after treatment reduced from 69% to 32% in the argatroban group, and from 64% to 51% in the batroxobin group (P < 0.0001 and P < 0.05, respectively). No significant change was observed in the heparin group. Angiography demonstrated the same trend. The percent area stenosis with thrombus at 60 minutes following balloon injury was 0.75% in the argatroban group, 18.9% in the heparin group (P < 0.05 vs argatroban), and 12.9% in the batroxobin group. Thrombus size at the treated site was smaller than that at the control site in all three groups (P < 0.05 vs control). In the coronary artery, angioscopic percent area obstruction by the thrombus before and 60 minutes after treatment reduced from 84% to 53% in the argatroban group, and from 86% to 68% in the batroxobin group (P < 0.0001 and P < 0.05, respectively). No significant change was observed in the heparin group. Angiography also demonstrated the same trend. The activated partial thromboplastin time (APTT) was prolonged to 189% of the control value with argatroban and to 1253% of the value with heparin (P < 0.0001). Fibrinogen was markedly reduced with batroxobin. These results showed that both the antithrombin agent and the defibrinogenating agent have a preventive effect on thrombus formation and the effect on thrombus size reduction, without marked prolongation of the APTT.