HEMODYNAMIC EFFECTS OF DOBUTAMINE & MILRINONE

多巴酚丁胺的血流动力学效应

• 批准号: 6304891
• 负责人: E MICHAEL GILBERT
• 金额: $ 0.16万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-12-01 至 2001-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6304891
• 关键词: beta antiadrenergic agent; clinical research; cyclic AMP; dobutamine; drug interactions; drug screening /evaluation; gene expression; heart disorder chemotherapy; heart failure; hemodynamics; human subject; human therapy evaluation; idiopathic dilated cardiomyopathy; pharmacokinetics; phosphodiesterase inhibitors

Chronic heart failure is often characterized by cardiac muscle cell contractile dysfunction, which is likely caused by alterations in heart muscle cell gene expression. Studies with cultured heart muscle cells have revealed fundamental differences in the gene expression programs leading to several different types of heart muscle cell failure. One common type of heart muscle failure has been associated with alterations in genes regulating hormone receptor function. In the failing human heart, there is a reduction in the number of a specific hormone receptor, designated the beta1-adrenergic receptor, and signaling failure normally mediated through a second receptor, designated the beta2-adrenergic receptor. These changes may serve to protect heart muscle cells, but they also diminish the ability of the heart muscle pump to respond to normal factors that would improve contractility in times of physical stress. Revolutionary studies performed by Dr. Gilbert and his associate, Dr. Bristow (now at the University of Colorado), demonstrated that treating heart failure with drugs that block the activity of b-adrenergic receptors leads to improvement in function of the heart pump. This study is designed to test the effects of a b-adrenergic receptor-blocking drug (dobutamine) and a drug that disrupts signaling events mediated through the b-adrenergic receptor (the phosphodiesterase inhibitor, milrinone) in an effort to dissect the complex mechanisms involved as heart muscle cells develop abnormalities of contraction in patients who develop heart failure.

慢性心力衰竭通常以心肌细胞收缩功能障碍为特征，这可能是由心肌细胞基因表达的改变引起的。 对培养的心肌细胞的研究揭示了导致几种不同类型心肌细胞衰竭的基因表达程序的根本差异。 一种常见的心肌衰竭与调节激素受体功能的基因改变有关。 在衰竭的人类心脏中，特定激素受体（称为β 1-肾上腺素能受体）的数量减少，并且通常通过第二受体（称为β 2-肾上腺素能受体）介导的信号传导失败。 这些变化可能有助于保护心肌细胞，但它们也会降低心肌泵对正常因素的反应能力，这些因素会在身体压力时改善收缩力。 吉尔伯特博士和他的同事布里斯托博士（现就职于科罗拉多大学）进行的革命性研究表明，用阻断b-肾上腺素受体活性的药物治疗心力衰竭可改善心脏泵的功能。 本研究旨在测试β-肾上腺素能受体阻断药（多巴酚丁胺）和一种破坏β-肾上腺素能受体介导的信号传导事件的药物（磷酸二酯酶抑制剂，米力农）的作用，以试图剖析心力衰竭患者心肌细胞发生收缩异常的复杂机制。