Pro-thrombotic Microparticles Generated by Pediatric Cardiopulmonary Bypass

儿科心肺转流术产生的促血栓微粒

基本信息

批准号：
9268044
负责人：
Andrew Duncan Joseph Meyer
金额：
$ 18.99万
依托单位：
UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-08-01 至 2019-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9268044
关键词：
Address Adult Anatomy Attenuated Award Biological Biological Assay Blood Blood Circulation Blood Platelets Blood specimen Cardiac Cardiopulmonary Bypass Caring Cells Child Child Support Childhood Clinical Clinical Research Coagulation Process Congenital Heart Defects Critical Care Critically ill children Data Defect Development Devices Diagnostic Event Family suidae Fibrin Generations Goals Heart Diseases Hemorrhage Human In Vitro Inflammatory Intervention Knowledge Lead Life Limb structure Lung diseases Maintenance Membrane Mentored Patient-Oriented Research Career Development Award Modeling Morbidity - disease rate National Heart, Lung, and Blood Institute Neonatal Neurologic Operative Surgical Procedures Organ failure Pathway interactions Patients Physicians Prevalence Pump Research Research Personnel Role Scientist Stress Stroke Technology Therapeutic Thrombelastography Thrombin Thromboembolism Thrombosis Time United States National Institutes of Health Vesicle Whole Blood blood pump career development clinically relevant experience improved in vitro Model innovation monocyte mortality pediatric patients programs public health relevance repaired shear stress skills translational scientist

项目摘要

DESCRIPTION (provided by applicant): My long-term goal is to become a pediatric critical care physician-scientist, a translational researcher committed to eliminate complications from advanced technology used to support critically ill children. My current emphasis is to focus on the pathophysiological basis of the untoward effects of cardiopulmonary bypass (CPB) devices on blood components. The Mentored Patient-Oriented Research Career Development Award (K23) will provide me with time to gather skills and knowledge as a necessary steps toward becoming an established, independent investigator. Over the past sixty years, support by Cardiopulmonary Bypass devices (CPB) has led to significant decreases in the mortality and morbidity of children suffering from life threatening heart or lung diseases. Although pump- related hemorrhage can be attenuated by maintenance of platelet levels, pump-dependent platelet and monocyte activation can lead to devastating stroke. This can be explained by the flow rates generated in extracorporeal blood pumps that increase the applied shear stress, this activates circulating monocytes and platelets. These activated cells will release platelet- and monocyte-derived microparticles (PMPs & MoMPs), small (0.1-1 micron) cell-derived membrane vesicles. PMPs and MoMPs released by applied shear stress may further contribute to thromboembolism by inducing a pro-thrombotic and pro-inflammatory state. My previous studies document the release of PMPs in an in vitro pediatric cardiopulmonary bypass circuit using porcine whole blood. We hypothesize that increased shear stress generated by a pediatric extracorporeal blood pump promotes pro-thrombotic microparticle release. This award will provide me with dedicated time to obtain new research skills in thrombosis and coagulation assays and experience in conducting pediatric studies. The goals of this research is to define how pump-produced PMPs and MoMPs contribute to thrombosis, from a pediatric model of CPB and from pediatric patients supported by CPB, in order to understand the mechanisms and subsequent therapeutics to address extracoporeal blood pump related thrombotic complications.

描述（由申请人提供）：我的长期目标是成为一名儿科重症监护医师科学家，一名致力于消除用于支持危重儿童的先进技术的并发症的转化研究人员。我目前的重点是关注病理生理学基础。指导患者导向的研究职业发展奖 (K23) 将为我提供时间来收集技能和知识，作为成为一名合格的医生的必要步骤。在过去的六十年里，心肺旁路装置 (CPB) 的支持显着降低了患有危及生命的心脏或肺部疾病的儿童的死亡率和发病率，尽管泵相关的出血可以通过维护来减轻。血小板水平的下降、泵依赖性血小板和单核细胞激活可导致毁灭性中风，这可以通过体外血泵产生的流速增加所施加的剪切应力来解释，这会激活循环。这些活化的细胞将释放血小板和单核细胞衍生的微粒（PMP 和 MoMP），施加剪切应力释放的小（0.1-1 微米）细胞衍生的膜囊泡可能通过诱导血栓栓塞。我之前的研究记录了使用猪整体的体外儿科心肺旁路回路中 PMP 的释放。我们追求通过儿科体外血泵产生的增加的剪切应力促进促血栓微粒释放。该奖项将为我提供专门的时间来获得血栓形成和凝血测定的新研究技能以及进行儿科研究的经验。本研究旨在通过 CPB 儿科模型和 CPB 支持的儿科患者来定义泵产生的 PMP 和 MoMP 如何导致血栓形成，以便了解解决体外血栓形成的机制和后续治疗方法。血泵相关的血栓并发症。