Ancrod decreases the frequency of cyclic flow variations and causes thrombolysis following acute coronary thrombosis

Abstract

The potential use of ancrod, a purified isolate from the venom of the Malaysian pit viper, Agkistrodon rhodostoma, in (1) decreasing the frequency of cyclic flow variations in severely stenosed canine coronary arteries and (2) causing thrombolysis of an acute coronary thrombus induced by a copper coll was evaluated. Open-chest, anesthetized dogs were used. Ancrod was given intravenously (8 U/kg) over 1 hour and caused a significant reduction in the frequency of cyclic flow variations (5.8 ± 0.7 to 3.6 ± 0.8 cyclic flow variations per 30 minutes, p < 0.05), whereas control animals failed to decrease the frequency of their cyclic flow variations over the same time period (5.3 ± 0.3 to 5.0 ± 0.4 cyclic flow variations per 30-minute period). Twenty-seven dogs had a coronary thrombus induced by a copper coll positioned directly in a major coronary artery; of these, four died of ventricular fibrillation prior to treatment, eight received an infusion of saline and showed no thrombolysis over 5 hours, and three died of ventricular fibrillation during the initial part of an intravenous infusion of ancrod. The remaining 12 dogs received ancrod intravenously (16 U/kg); six demonstrated lysis of the coronary thrombus (mean time to lysis, 65 ± 20 minutes). The concentrations of ancrod used in these studies produced a severe decreaso in systemic fibrinogon concentration and a significant decrease in the inhibitor of plasminogen activator levels. Thus, ancrod decreases the frequency of cyclic flow variations in stenosed canine coronary arterles and may cause coronary thrombolysis in approximately 50% of animale within 65 ± 20 minutes of its intravenous administration.