Abstract 11269: Recombinant Soluble Thrombomodulin in Prolonged Porcine Cardiac Arrest
| Autor: | Boya Zhang, Brendan McCracken, Danielle Leander, Carmen Colmenero, Nicholas Greer, Cindy H Hsu, James Cranford, Mohamad Tiba, Robert W Neumar, Colin Greineder |
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| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | Circulation. 144 |
| ISSN: | 1524-4539 0009-7322 |
| DOI: | 10.1161/circ.144.suppl_2.11269 |
| Popis: | Introduction: Sudden Cardiac Arrest (CA) affects more than 400,000 people per year in the United States. Although a third of these patients survive to hospital admission, another 60-70% go on to die due to failed recovery of vital organ function. Microvascular thrombosis has been suggested as a potential contributor to prolonged organ dysfunction, but no antithrombotic therapies have been shown to be beneficial and coagulofibrinolytic abnormalities in prolonged CA remain poorly understood. Objectives: To establish key biomarkers of porcine coagulation and fibrinolysis in the setting of prolonged CA and cardiopulmonary resuscitation (CPR) and test the ability of ART-123 (recombinant human thrombomodulin alpha) to reverse these abnormalities. Methods: 15 pigs (n=5 per group) underwent 8 minutes of no-flow CA followed by 50 minutes of mechanical CPR. Animals were randomized to receive saline or ART-123 (~1mg/kg) pre-arrest (5 minutes prior to ventricular fibrillation) or post-arrest (2 minutes after initiation of CPR). Results: Robust and ongoing activation of coagulation and fibrinolysis were detected throughout the resuscitation. After 50 minutes of CPR, plasma tests suggested consumptive coagulopathy, while whole blood testing (thromboelastography) indicated a persistent hypercoagulable state. ART-123 had a clear anticoagulant effect irrespective of timing (TAT complexes 381±25 vs. 238±18 vs. 226±12, p Conclusion: Our porcine CA model provides an excellent platform for evaluating antithrombotic interventions. Plasma testing after prolonged CA/CPR suggests consumptive coagulopathy, although TEG indicates a persistent hypercoagulable state. ART-123 given before no-flow or just after CPR demonstrates antithrombotic effects, although the specific modes of action depending on the timing of administration. |
| Databáze: | OpenAIRE |
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