Pro-thrombotic Microparticles Generated by Pediatric Cardiopulmonary Bypass

儿科心肺转流术产生的促血栓微粒

• 批准号: 9114153
• 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
• 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/9114153
• 关键词: Address; Adult; 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; Health; 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; base; blood pump; career development; clinically relevant; experience; improved; in vitro Model; innovation; monocyte; mortality; pediatric patients; programs; repaired; shear stress; skills

 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重症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体外循环 (CPB) 装置对血液成分产生不良影响的病理生理学基础。以患者为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，这是成为一名成熟的独立研究者的必要步骤。在过去的六十年里，心肺旁路设备 (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。虽然泵相关的出血可以通过维持血小板水平来减轻，但是泵依赖性血小板和单核细胞活化可以导致毁灭性的中风。这可以通过体外血泵产生的流速来解释，该流速增加了施加的剪切应力，这激活了循环单核细胞和血小板。这些激活的细胞将释放血小板和单核细胞衍生的微粒（PMP 和 MoMP）、小（0.1-1 微米）细胞衍生的膜囊泡。施加剪切应力释放的 PMP 和 MoMP 可能通过诱导促血栓和促炎症状态进一步促进血栓栓塞。我之前的研究记录了使用猪全血在体外儿科心肺旁路回路中释放 PMP 的情况。我们假设儿科体外血泵产生的剪切应力增加会促进促血栓微粒的释放。该奖项将为我提供专门的时间来获得血栓和凝血测定方面的新研究技能以及进行儿科研究的经验。本研究的目标是通过 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泵相关血栓并发症的机制和后续治疗方法。