Myocardial Flow Enhancement with Drag Reducing Polymers: Microvascular Mechanisms

使用减阻聚合物增强心肌血流：微血管机制

• 批准号: 7609086
• 负责人: John J Pacella
• 金额: $ 12.62万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7609086
• 关键词: Acute; Address; Adhesions; Area; Arts; Attenuated; Automobile Driving; Behavior; Biological Preservation; Blood; Blood Vessels; Blood Volume; Blood capillaries; Blood flow; Canis familiaris; Capillary Resistance; Cardiology; Cause of Death; Cell Communication; Cell Cycle Kinetics; Cells; Classification; Clinical; Complex; Contrast echocardiography procedure; Coronary; Coronary Stenosis; Coronary artery; Coronary heart disease; Data; Development; Disease; Endothelial Cells; Erythrocytes; Experimental Animal Model; Experimental Designs; Failure; Fellowship; Funding; Goals; Health; Health Benefit; Hematocrit procedure; Hemorrhagic Shock; Hospitalization; Imaging Techniques; In Vitro; Individual; Intervention; Investigation; Kinetics; Knowledge; Lead; Learning; Leukocytes; Liquid substance; Measurement; Measures; Mechanics; Mediating; Methodology; Microbubbles; Microcirculation; Microscopic; Microspheres; Modeling; Molecular Weight; Morphology; Myocardial; Myocardial Ischemia; Myocardial perfusion; Organ; Oxygen; Perfusion; Physics; Physiological; Physiology; Plasma; Polymers; Principal Investigator; Process; Property; Radiolabeled; Rattus; Research; Research Personnel; Resistance; Rest; Rheology; Simulate; Stenosis; Techniques; Testing; Therapeutic; Tissues; Tracer; Training; Translations; Ultrasonography; Vascular System; Vascular resistance; Vasodilation; Vasomotor; Width; Work; abstracting; acute coronary syndrome; animal data; arteriole; capillary; clinical application; cost; density; design; falls; fluid flow; hemodynamics; improved; in vivo; insight; intravital microscopy; macromolecule; novel strategies; novel therapeutics; pressure; programs; radiotracer; resistance mechanism; skills; tissue oxygenation; tool; treatment strategy

DESCRIPTION (provided by applicant): Coronary heart disease is the leading cause of death worldwide. In 2001 there were 2 million CHD hospitalizations with an annual cost of $133 billion. Current strategies for the treatment of acute coronary syndromes, which includes restoring epicardial coronary artery patency, do not consistently restore microvascular perfusion, which has adverse clinical consequences. Drag-reducing polymers (DRPs) may fill this void. DRPs reduce vascular resistance, potentially by targeting the rheology and hydrodynamics of blood flow. Under AHA support, the Principal Investigator has studied the effects of DRPs on myocardial perfusion in the setting of graded canine coronary stenoses. He has found that minute intravascular concentrations of DRPs normalize myocardial perfusion and improve coronary flow reserve by decreasing capillary resistance, and this may provide a novel approach for the treatment of coronary heart disease. Traditionally, DRPs are known to augment pipe flow through reductions in fluid resistance. In vascular systems, similar mechanisms are theorized but the precise microvascular mechanism of action is unknown. Having established the potential health benefits of DRPs in experimental animal models, further clinical development as a therapeutic strategy will require a greater understanding of its microvascular mechanisms. Accordingly, this research program builds on the Pi's intact animal data by investigating DRPs effects at the microcirculatory level. The Principal Investigator will learn sophisticated tools for intravital microcirculation research, including measurements of microvascular pressure, microvascular hematocrit, and red cell and leukocyte kinetics. These techniques will be used to determine whether DRPs enhance perfusion through (1) Alterations in hydrodynamics by increasing precapillary driving pressure; (2) Changing microvascular red cell distribution; (3) Altering leukocyte-endothelial interactions; or a combination thereof. The Principal Investigator's short term goal is to gain a fund of knowledge in the field of the microcirculation and to learn the techniques to answer the questions posed by this proposal. He will then apply his new skill set to address questions in his field of clinical expertise, interventional cardiology. His ultimate goal is to improve treatments aimed at the coronary microcirculation, including treatment of coronary 'no-reflow,' by delving into its microvascular mechanisms. By interrogating the microvascular mechanisms of DRPs, this proposal provides a vehicle to learn these methodologies. (End of Abstract)

描述（由申请人提供）： 冠心病是全球死亡的主要原因。在2001年，有200万个冠心病住院治疗，每年成本为1330亿美元。当前治疗急性冠状动脉综合征的策略，包括恢复心外膜冠状动脉通畅，并不能始终恢复微血管灌注，这具有不良的临床后果。减速聚合物（DRP）可能会填充此空隙。 DRP可能通过靶向血流的流变学和流体动力学来降低血管抗性。在AHA的支持下，首席研究者研究了DRP对分级犬冠状动脉炎症的影响。他发现，DRP的细分血管内浓度通过降低毛细管耐药性来使心肌灌注正常化，并改善冠状动脉流量储备，这可能为治疗冠状动脉疾病的治疗提供了一种新颖的方法。传统上，已知DRP可以通过降低流体耐药性来增加管道流动。在血管系统中，相似的机制是理论上的，但精确的微血管作用机理尚不清楚。在实验动物模型中建立了DRP的潜在健康益处后，作为治疗策略的进一步临床发展将需要对其微血管机制有更多了解。因此，该研究计划通过在微循环水平上研究DRPS效应来建立PI完整的动物数据。首席研究者将学习用于插入微循环研究的复杂工具，包括微血压，微血管血细胞比容的测量以及红细胞和白细胞动力学。这些技术将用于确定DRP是否通过（1）通过增加毛细血管前驾驶压力来改变（1）流体动力学的变化； （2）改变微血管红细胞分布； （3）改变白细胞 - 内皮相互作用；或其组合。主要研究者的短期目标是获得微循环领域的知识基金，并学习回答该提议提出的问题的技术。然后，他将使用他的新技能设置来解决临床专业知识领域的问题，即介入性心脏病学。他的最终目标是改善针对冠状动脉微循环的治疗方法，包括通过探究其微血管机制来治疗冠状动脉“无流量”。通过询问DRP的微血管机制，该建议提供了学习这些方法的工具。 （抽象的结尾）