RIGHT VENTRICULAR DYSFUNCTION AND TREATMENT

右心室功能障碍和治疗

• 批准号: 6388533
• 负责人: Marc J Semigran
• 金额: $ 11.25万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-12 至 2004-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6388533
• 关键词: apoptosis; cardiac myocytes; clinical research; exercise; heart disorder; heart disorder chemotherapy; heart failure; heart function; heart ventricle; human subject; human therapy evaluation; inhalation drug administration; nitric oxide; phosphodiesterase inhibitors; phosphodiesterases; pulmonary artery; pulmonary hypertension; vasodilation

Heart failure represents the results of a variety of cardiovascular diseases in which the initial insult to the myocardium may either be identifiable, such as a myocardial infarction, or unknown, such as in dilated cardiomyopathy. In either case, the occurrence of injury to the myocardium leads to an inexorable course of myocardial dysfunction. While most previous investigations have concentrated on the abnormalities in left ventricular function, there is evidence that right ventricular (RV) function is a more important determinant of patients symptoms and prognosis. Few therapies currently exist to improve RV performance, as currently used systemic vasodilator therapy can cause hypotension when nonselective pulmonary vasodilators are added to a patient's therapeutic regimen. Nitric oxide (NO) activates vascular smooth muscle cell soluble guanylate cyclase leading to vasodilation. The vasodilator effect of NO is limited in time by its rapid binding to, and inactivation by hemoglobin. In preliminary studies, inhaled NO has been demonstrated to be a selective pulmonary vasodilator which can improve cardiac performance and exercise capacity in heart failure patients. The goal of this proposal is to combine type 5 (cGMP- specific) phosphodiesterase inhibiton with inhaled NO to: 1. Assess the acute alterations in right ventricular function, overall cardiac performance and exercise capacity in heart failure patients treated with the combination of inhaled NO and the type 5 phosphodiesterase inhibitor sildenafil. 2. Assess the acute and chronic effects of selective pulmonary vasodilation with inhaled nitric oxide and type 5 phosphodiesterase inhibition on pulmonary artery resistance and morphology in patients with pulmonary hypertension due to pulmonary vascular disease or to left heart failure. 3. Assess the effects of acute and chronic pulmonary vasodilator and the subsequent decrease in wall stress on the activity of proteins which regulate myocyte apoptosis.

心力衰竭代表了多种心血管疾病的结果，其中最初对心肌的侮辱可能是可识别的，例如心肌梗塞或未知的心肌，例如在扩张的心肌病中。 无论哪种情况，心肌受伤的发生都导致心肌功能障碍的不可动性。尽管大多数以前的研究都集中在左心室功能的异常上，但有证据表明右心（RV）功能是患者症状和预后的更重要的决定因素。 当前使用的全身血管扩张剂治疗当前，目前几乎没有疗法可提高RV性能，当将非选择性肺血管扩张剂添加到患者的治疗方案中时，可能会导致低血压。 一氧化氮（NO）激活血管平滑肌细胞可溶性鸟苷酸环化酶导致血管舒张。 NO的血管扩张效应在时间上的快速结合并通过血红蛋白灭活而受到限制。 在初步研究中，吸入NO已被证明是一种选择性的肺血管扩张剂，可以提高心力衰竭患者的心脏性能和运动能力。 该提案的目的是将5型（CGMP-特异性）磷酸二酯酶抑制剂与吸入no结合：1。评估右心室功能的急性改变，整体心力衰竭和患者的心力衰竭患者的急性变化，与吸入的NO和5型5磷酸二磷酸酯酶抑制剂silditeitor sildenentenafil治疗。 2。通过吸入一氧化氮和5型磷酸二酯酶抑制对肺动脉高压的肺动脉耐药性和形态的选择性肺血管舒张的急性和慢性作用。 3。评估急性和慢性肺血管扩张剂的影响，以及随后壁应力对调节心肌细胞凋亡的蛋白质活性的降低。