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: 7363611
• 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/7363611
• 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; Condition; 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; Numbers; 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; Urination; Vascular System; Vascular resistance; Vasodilation; Vasomotor; Width; Work; abstracting; acute coronary syndrome; animal data; arteriole; capillary; clinical application; concept; 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

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）：