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Iloprost and echistatin protect platelets during simulated extracorporeal circulation
A Bernabei1, N Gikakis, M A Kowalska
1Harrison Department of Surgery, School of Medicine, University of Pennsylvania, Philadelphia.
The Annals of Thoracic Surgery
|January 1, 1995
Summary
Combining iloprost with a disintegrin offers superior platelet protection during cardiopulmonary bypass. This strategy effectively inhibits platelet activation and preserves function, reducing bleeding risks.
Area of Science:
- Cardiovascular Science
- Hematology
- Biomedical Engineering
Background:
- Platelet inhibition is crucial for protecting platelets and normalizing bleeding times during cardiopulmonary bypass.
- Iloprost (prostacyclin analogue) and disintegrins (echistatin, RO43-5054) inhibit platelets via distinct mechanisms.
- Optimizing platelet protection requires exploring combination therapies with reduced drug dosages.
Purpose of the Study:
- To evaluate the combined efficacy of reduced doses of iloprost and disintegrins (echistatin or RO43-5054) in protecting platelets during simulated extracorporeal circulation.
- To determine if combination therapy offers superior platelet protection compared to individual agents.
- To assess the impact of these combinations on platelet activation markers and function.
Main Methods:
- Thirty-five recirculation studies were conducted using fresh, heparinized human blood in an extracorporeal perfusion circuit with a membrane oxygenator.
- Iloprost's effect on platelet cyclic adenosine monophosphate (cAMP) was measured.
- Platelet adhesion, beta-thromboglobulin release, and aggregation to adenosine diphosphate (ADP) were assessed for individual drugs and combinations.
Main Results:
- Combinations of iloprost and fibrinogen receptor antagonists (disintegrins) at reduced doses submaximally increased platelet cAMP.
- Platelet adhesion and beta-thromboglobulin release were completely inhibited by drug combinations, but only partially by individual agents.
- Combinations completely inhibited platelet aggregation to ADP, with platelets retaining full ADP sensitivity after drug removal.
Conclusions:
- Combinations of iloprost and fibrinogen receptor antagonists at clinically safe doses effectively inhibit platelet activation during in vitro extracorporeal circulation.
- This combined approach completely preserves platelet function, offering a promising strategy for managing bleeding risks.
- The findings support the use of reduced-dose combination therapy for enhanced platelet protection in extracorporeal procedures.