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Kinins and thrombolysis
J Swies1, S Chłopicki, R J Gryglewski
1Department of Pharmacology, University School of Medicine, Kraków, Poland.
Insights
Kallikrein and captopril demonstrate thrombolytic effects in cats, dissipating blood clots. This action is linked to prostacyclin release, highlighting a potential therapeutic pathway for thrombosis.
Area of Science:
- Pharmacology
- Cardiovascular Research
- Biochemistry
Background:
- Extracorporeal circulation models are used to study cardiovascular interventions.
- Understanding the mechanisms of blood clot dissolution (thrombolysis) is crucial for treating thrombotic diseases.
Purpose of the Study:
- To investigate the thrombolytic properties of kallikrein and captopril in a feline extracorporeal circulation model.
- To elucidate the biochemical pathways involved in kallikrein-induced thrombolysis.
Main Methods:
- Assaying arterial blood pressure and thrombolysis in cats undergoing extracorporeal circulation.
- Administering kallikrein, captopril, and aprotinin to assess their effects on preformed blood clots.
- Incubating thrombolytic agents with blood to identify unstable principles and their decomposition kinetics.
- Investigating the role of aspirin in inhibiting the generation of the thrombolytic principle.
Main Results:
- Kallikrein and captopril exhibited hypotensive and thrombolytic properties, dissolving blood clots on collagen strips.
- A lower dose of captopril potentiated kallikrein's thrombolytic effect, while aprotinin inhibited it.
- Kallikrein-induced thrombolysis involved an unstable factor, decomposed by blood within 15 minutes at 37°C.
- Aspirin pretreatment inhibited the generation of this thrombolytic principle.
Conclusions:
- The findings suggest that kallikrein-induced thrombolysis is mediated by prostacyclin, released by kinins.
- Prostacyclin's platelet-suppressant and fibrinolytic activities contribute to thrombolysis.
- This study identifies a potential therapeutic mechanism involving kinin-prostacyclin interaction for managing thrombosis.
Abstract:
In cats with extracorporeal circulation arterial blood pressure and thrombolysis were assayed. In this model apart from their hypotensive properties kallikrein (3-10 units/kg, i.v.) and captopril (> 200 micrograms/kg, i.v.) dissipated blood clots which were preformed on superfused collagen strips. Captopril at a lower dose of 50 micrograms/kg i.v. potentiated the thrombolytic effect of kallikrein while aprotinin (100,000 unit/kg, i.v.) abolished it. Thrombolysis by kallikrein was mediated by an unstable principle which was decomposed by blood during 15 min of incubation at 37 degrees C. Generation of this principle was inhibited by pretreatment of animals with aspirin (50 mg/kg, i.v.). The above analysis points to prostacyclin which owing to its platelet-suppressant and fibrinolytic properties induces thrombolysis when released by kinins.