Pilot study of the efficacy of a thrombin inhibitor for use during cardiopulmonary bypass
| Autor: | Veronica S. Law, Steven Coutre, Abelardo DeAnda, Lawrence L.K. Leung, Marc R. Moon, Linda C. Griffin, Conrad M. Vial, Masashi Komeda, D. Craig Miller |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
Pulmonary and Respiratory Medicine
medicine.drug_class Polynucleotides Oligonucleotides Activated clotting time Pilot Projects law.invention Dogs Thrombin Pharmacokinetics law medicine Cardiopulmonary bypass Animals Infusions Intravenous Blood Coagulation Chromatography High Pressure Liquid Prothrombin time Cardiopulmonary Bypass Dose-Response Relationship Drug medicine.diagnostic_test Heparin business.industry Anticoagulant Aptamers Nucleotide surgical procedures operative Coagulation Anesthesia Prothrombin Time Surgery Cardiology and Cardiovascular Medicine business circulatory and respiratory physiology medicine.drug |
| Zdroj: | The Annals of Thoracic Surgery. 58:344-350 |
| ISSN: | 0003-4975 |
| DOI: | 10.1016/0003-4975(94)92206-3 |
| Popis: | Heparin is normally used for anticoagulation during cardiopulmonary bypass (CPB), but its use is contraindicated in patients with a history of heparin-induced thrombocytopenia, heparin-provoked thrombosis, or both. Heparin therapy can also be ineffective due to heparin resistance. A short-acting, oligonucleotide-based thrombin inhibitor (thrombin aptamer) may potentially serve as a substitute for heparin in these and other clinical situations. We tested a novel thrombin aptamer in a canine CPB pilot study to determine its anticoagulant efficacy, the resultant changes in coagulation variables, and the aptamer's clearance mechanisms and pharmacokinetics. Seven dogs were studied initially: Four received varied doses of the aptamer (to establish the pharmacokinetic profile) and 3 received heparin. Subsequently, 4 other dogs underwent CPB, receiving a constant infusion of the aptamer before CPB (to characterize the baseline coagulation status), with partial CPB and hemodilution, during 60 minutes of total CPB, and, finally, after a 2-hour recovery period. At a 0.5 mg.kg-1.min-1 dose, the activated clotting time rose with aptamer infusion from 106 +/- 12 seconds to 187 +/- 8 seconds (+/- 1 standard deviation) (p = 0.014), increased further with hemodilution (to 259 +/- 41 seconds; p = 0.017), and was even more prolonged during total CPB (> 1,500 seconds; p < 0.001). This later increase in the activated clotting time paralleled a rise in the plasma concentration of the thrombin aptamer during total CPB, as determined by high-performance liquid chromatography.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Databáze: | OpenAIRE |
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