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

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和死亡为高潮，虽然随着药物治疗药物的引入，某些患者的生存率延长了，但CPH仍然是致命的。该项目的长期目标是确定右心房和心室从代偿性肥厚到扩张性功能障碍的发展过程中，由于长期暴露于肺动脉压力升高，右心房和心室发生的生物力学和分子变化。采用动物慢性右心室压力过载和化学致肺动脉高压（单罗塔碱吡咯）两种标准实验模型，建立慢性肺动脉高压和右心衰模型。右心力学将采用同步室导尿管技术、三维右心室应力应变图的磁共振成像有限元分析和心肌肾上腺素能受体和钙处理蛋白的评估来研究。此外，潜在的治疗选择分子调节（慢性22-肾上腺素能刺激）和血流动力学卸载（心房分流）将被研究。右心衰是慢性肺动脉高压患者不可避免的死亡原因。本项目旨在确定右心房和心室从代偿性肥厚发展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，潜在的治疗选择分子调节（慢性22-肾上腺素能刺激）和血流动力学卸载（心房分流）将被研究。

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.