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Ancrod decreases the frequency of cyclic flow variations and causes thrombolysis following acute coronary thrombosis
Insights
Ancrod, derived from Malaysian pit viper venom, effectively reduced cyclic flow variations in stenosed canine coronary arteries. It also demonstrated potential for coronary thrombolysis, dissolving clots in about half of treated dogs.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Venom-derived Therapeutics
Background:
- Cyclic flow variations (CFVs) are critical in stenosed coronary arteries.
- Acute coronary thrombus formation poses a significant clinical challenge.
- Ancrod, a snake venom enzyme, has anticoagulant properties.
Purpose of the Study:
- To evaluate ancrod's efficacy in reducing CFVs in stenosed canine coronary arteries.
- To assess ancrod's thrombolytic potential on induced acute coronary thrombi.
- To investigate ancrod's effect on fibrinogen and plasminogen activator inhibitor levels.
Main Methods:
- Ancrod was administered intravenously to anesthetized dogs with induced coronary artery stenosis and thrombus.
- CFV frequency was measured before and after ancrod treatment.
- Thrombolysis was assessed in dogs with induced coronary thrombi receiving ancrod or saline.
- Fibrinogen and plasminogen activator inhibitor levels were monitored.
Main Results:
- Ancrod significantly reduced the frequency of CFVs in stenosed arteries (p < 0.05).
- Ancrod achieved coronary thrombolysis in 6 out of 12 dogs within 65 ± 20 minutes.
- Treatment led to decreased systemic fibrinogen and plasminogen activator inhibitor levels.
Conclusions:
- Ancrod effectively reduces cyclic flow variations in stenosed coronary arteries.
- Ancrod demonstrates significant coronary thrombolytic activity in a canine model.
- Ancrod's mechanism involves reduction of fibrinogen and plasminogen activator inhibitor.
Abstract:
The potential use of ancrod, a purified isolate from the venom of the Malaysian pit viper, Agkistrodon rhodostoma, in decreasing the frequency of cyclic flow variations in severely stenosed canine coronary arteries and causing thrombolysis of an acute coronary thrombus induced by a copper coil 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 less than 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 coil 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 decrease in systemic fibrinogen 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 arteries and may cause coronary thrombolysis in approximately 50% of animals within 65 +/- 20 minutes of its intravenous administration.