One focus of my research has been on developing a better understanding of the pharmacology of hemostatically-active drugs. In the past, this has resulted in funded projects which evaluated the pharmacokinetics of the low molecular weight heparin tinzaparin, isolated and characterized heparin from fish skins, studied the role of leukocytes in mediating platelet activation by antibodies generated in heparin-induced thrombocytopenia and characterized the effectiveness of salicylamide and arylamide derivatives to neutralize the anticoagulant, antithrombotic and hemorrhagic effects of heparin and low molecular weight heparin. More recent studies have focused on using prothrombin complex concentrates to reverse bleeding induced by non-vitamin K antagonist oral anticoagulants and on characterizing the activity of biosimilar low molecular weight heparins.
A second focus of my research is on the evaluation of platelet function. This has been carried out primarily through the use of flow cytometry. I have used this technique from a basic science standpoint in the study of heparin-induced thrombocytopenia as well as to characterize the effectiveness of novel antiplatelet agents such as allosteric PAR-1 inhibitors and aspirin-phosphatidylcholine complexes. This technique has also been applied to translational/clinical studies evaluating markers of platelet activation and levels of microparticles in patients suspected of having heparin-induced thrombocytopenia, patients with atrial fibrillation, infants suspected of having necrotizing enterocolitis and in patient populations treated with on-pump or off-pump revascularization, left ventricular assist device implantation, intravascular brachytherapy, drug-eluting stent placement, or serotonin reuptake inhibitors.
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Comparison of Vagus Nerve Stimulation with a Cuff Electrode in the Neck to the Upper Chest Below the Recurrent Laryngeal Nerve - Medtronic Inc. CRDM Program
This project was recently completed. We have found that stimulation of the right vagus nerve in the upper-thorax below the recurrent laryngeal nerve consistently induced beneficial parasympathetic effects while eliminating the side effects of vocal cord and neck muscle activation which occur with stimulation of the vagus nerve in the neck. Our group was recently granted a provisional patent in this area working through the VA Technology Transfer Department; we are currently in the process of finalizing the utility patent for this invention.
Selective Vagus Nerve Stimulation using the Utah Slanted Electrode Array (USEA) – Blackrock Microsystems NIH STTR Phase I Grant
The long-term goal of this project is to restore autonomic balance to the failing heart through electrical stimulation of the vagus nerve using an implanted microelectrode array. A 96 electrode array, comprised of 96 individual microelectrodes in a 0.5 cm2 area, was used for stimulation of the vagus nerve in the neck to produce selective heart rate slowing without side effects in anesthetized canines. We are currently in the process of analyzing the data in this study. We plan to submit the grant for Phase II.
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Research focus is in the field of cardiovascular disorders and anticoagulation targeting mechanisms of vascular occlusion, role of cellular activation and inflammation in thrombosis, development of new anticoagulants, and optimization of clinical laboratory coagulation testing. Basic science, translational, and clinical investigations have centered on ventricular assist devices (VADs), total artificial heart, coronary artery bypass surgery, and heparin-induced thrombocytopenia (HIT). Additional programs address anticoagulant drugs such as heparin, low molecular weight heparins, fondaparinux, argatroban, bivalirudin, and the new oral anticoagulants. Recent specific interests are centered on the discovery of biomarkers to predict thrombotic events in patients with implanted VADs; pathophysiologic mechanisms, laboratory diagnosis and clinical management of HIT; and development of clinical laboratory tests for monitoring the new anticoagulants. These programs have led to participation in writing national and international consensus guidelines and service to the Heparin Advisory Panel of the Expert Committee on Blood and Blood Products of the United States Pharmacopeia.
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