Comparative efficacy of in vitro and in vivo metabolized aspirin in the DeBakey ventricular assist device
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Ventricular assist devices (VADs) are implanted in patients with end-stage heart failure to provide both short- and long-term hemodynamic support. Unfortunately, bleeding and thromboembolic complications due to the severely disturbed, dynamic flow conditions generated within these devices require complex, long-term antiplatelet and anticoagulant therapy. While several studies have examined the effectiveness of one such agent, aspirin, under flow conditions, data comparing the efficacy of in vitro and in vivo metabolized aspirin is lacking. Two sets of studies were conducted in vitro with purified human platelets circulating for 30 min in a flow loop containing the DeBakey VAD (MicroMed Cardiovascular, Houston, TX, USA): (a) 20 μM aspirin was added exogenously in vitro to platelets isolated from aspirin-free subjects, and (b) platelets were obtained from donors 2 h (n = 14) and 20 h (n = 13) after ingestion of 1,000 mg aspirin. Near real-time platelet activation state (PAS) was measured with a modified prothrombinase-based assay. Platelets exposed to aspirin in vitro and in vivo (metabolized) showed 28.2 and 25.3 % reduction in platelet activation rate, respectively, compared to untreated controls. Our results demonstrate that in vitro treatment with antiplatelet drugs such as aspirin is as effective as in vivo metabolized aspirin in testing the effect of reducing shear-induced platelet activation in the VAD. Using the PAS assay provides a practical in vitro alternative to in vivo testing of antiplatelet efficacy, as well as for testing the thrombogenic performance of devices during their research and development.
KeywordsAspirin Ventricular assist devices Platelets Thrombin
The authors thank Dr. Sheela George for her assistance with experiments and the Stony Brook University Medical Center Chemistry Lab for salicylate measurements. This work was supported by the National Institute of Biomedical Imaging and Bioengineering Quantum Grant (Award No. 5U01EB012487-00, Dr. Bluestein).
Drs. Bluestein and Slepian were members of the Scientific Advisory Board of MicroMed Cardiovascular, Inc at the time of conduct of this investigation. The other authors report no conflicts of interest.
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