RIGHT HEART FUNCTION IN PULMONARY HYPERTENSION WITH BETA-AGONIST AND ATRIAL SHUNT

β 受体激动剂和心房分流术治疗肺动脉高压时的右心功能

• 批准号: 7790618
• 负责人: MARC R MOON
• 金额: $ 38万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7790618
• 关键词: 3-Dimensional; Address; Adrenergic Agents; Adrenergic Receptor; Agonist; Animals; Biomechanics; Blood; Calcium; Calcium Channel Blockers; Cardiac Output; Catheters; Cause of Death; Cessation of life; Chronic; Clenbuterol; Contracts; Decision Making; Development; Disease; Equilibrium; Evaluation; Experimental Models; Exposure to; Finite Element Analysis; Foundations; Functional disorder; Goals; Heart; Heart Atrium; Heart failure; Heating; Hypertrophy; Inferior; Laboratories; Lead; Life; Lung; Magnetic Resonance Imaging; Maps; Mechanics; Medical; Molecular; Motion; Myocardial; Operative Surgical Procedures; Oxygen; Pathology; Patients; Pattern; Physiologic intraventricular pressure; Play; Proteins; Pulmonary Hypertension; Right Atrial Function; Right atrial structure; Right ventricular structure; Right-On; Role; Shock; Shunt Device; Solid; Stress; Structure; Survival Rate; Techniques; Technology; Therapeutic; Therapeutic Agents; Time; Torsion; Tricuspid valve structure; Vena caval structure; Ventricular; Work; adrenergic; base; design; direct patient care; heart function; hemodynamics; monocrotaline pyrrole; novel; pressure; response; success

DESCRIPTION (provided by applicant): Chronic pulmonary hypertension culminates in right heart failure and death in the majority of patients, and while survival rates for selected patients have been prolonged with the introduction of medical therapeutic agents, CPH remains invariably fatal. The long-range goals of this project are to determine the biomechanical and molecular changes that occur in the right atrium and ventricle during their progression from compensatory hypertrophy to dilated dysfunction consequent to prolonged exposure to elevated pulmonary pressures. Using two standard experimental models of chronic right ventricular pressure overload and chemically-induced pulmonary hypertension (monocrotaline pyrrole) in animals, chronic pulmonary hypertension and right heart failure will be created. Right heart mechanics will be studied using simultaneous bichamber conductance catheter technology, magnetic resonance imaging with finite element analysis for 3-dimensional right ventricular stress-strain mapping, and assessment of myocardial adrenergic receptors and calcium handling proteins. In addition, potential therapeutic options for molecular modulation (chronic 22-adrenergic stimulation) and hemodynamic unloading (interatrial shunting) will be studied. NARRATIVE: Right heart failure is the inevitable cause of death in patients with chronic pulmonary hypertension. This project seeks to determine the biomechanical and molecular changes that occur in the right atrium and ventricle during their progression from compensatory hypertrophy to dilated dysfunction. In addition, potential therapeutic options for molecular modulation (chronic 22-adrenergic stimulation) and hemodynamic unloading (interatrial shunting) will be studied.

描述（由申请人提供）：慢性肺动脉高压在大多数患者中以右心衰竭和死亡告终，虽然随着药物治疗剂的引入，选定患者的存活率已经延长，但CPH仍然总是致命的。 该项目的长期目标是确定在右心房和心室从代偿性肥大进展到扩张性功能障碍期间发生的生物力学和分子变化，这是由于长期暴露于肺动脉压升高。 使用动物慢性右心室压力超负荷和化学诱导肺动脉高压（野百合碱吡咯）的两种标准实验模型，将创建慢性肺动脉高压和右心衰竭。将使用同步双腔电导导管技术、磁共振成像和三维右心室应力-应变标测的有限元分析以及心肌肾上腺素能受体和钙处理蛋白评估研究右心力学。 此外，还将研究分子调节（慢性22-肾上腺素能刺激）和血流动力学卸载（房间分流）的潜在治疗选择。叙述：右心衰竭是慢性肺动脉高压患者死亡的必然原因。本项目旨在确定右心房和右心室从代偿性肥大到扩张性功能障碍过程中发生的生物力学和分子变化。 此外，还将研究分子调节（慢性22-肾上腺素能刺激）和血流动力学卸载（房间分流）的潜在治疗选择。