Antithrombic Mechanisms of Viper Venom Platelet Inhibitory Factor in the Rat Myocardial Ischemia-Reperfusion Injury Model

Background: Myocardial ischemia-reperfusion injury (MIRI) exacerbates thrombosis and platelet hyperactivation postrevascularization, with limited therapeutic efficacy of existing antiplatelet agents. Agkistrodon halys venom platelet inhibitor (AHVPI) shows uncharacterized antithrombotic potential. This study evaluates AHVPI’s mechanistic regulation of key platelet biomarkers and hemostatic parameters in a rat MIRI model. Objectives: To explore the antithrombic mechanisms of AHVPI in a rat model of MIRI. Materials and Methods: Thirty male Sprague-Dawley rats were randomized to the sham operation (n = 6), MIRI (n = 6), and AHVPI groups (n = 18). The left anterior descending coronary artery was ligated to form the MIRI model. The AHVPI group included three subgroups (low-dose, medium-dose, and high-dose groups), which were sublingually administered AHVPI at doses of 0.05, 0.1, and 0.2 mg/kg body weight, respectively (six rats per subgroup). Electrocardiographic changes were monitored via the RM6240 biological signal acquisition system. An enzyme-linked immunosorbent assay was used to measure the plasma levels of platelet membrane glycoprotein VI (GPVI) and P-selectin. Thromboelastography (TEG® 5000) was used to assess the clot formation time (K), coagulation time (R), α angle (A), and maximum amplitude (MA) in the rat blood. Whole-blood and plasma viscosity was measured using a cone-plate viscometer, whereas turbidimetry was used to determine the platelet aggregation rate. Results: Compared with those in the MIRI group, A and MA values (p < .05), blood viscosity, aggregation amplitude, platelet aggregation rate (p < .05), and the GPVI and P-selectin expression levels (p < .05) were prominently lower, and both the K and R values were markedly greater in the medium-dose and high-dose AHVPI groups. Conclusion: AHVPI considerably inhibits platelet activity, alleviates MIRI-associated hemorheological properties, and mitigates the adverse effects of MIRI in the MIRI rat model.