MYOCARDIAL DEPRESSION FOLLOWING CARDIOPULMONARY BYPASS

心肺转流术后心肌抑制

• 批准号: 2231246
• 负责人: Mitchell Simon Finkel
• 金额: $ 21.29万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-01-01 至 1997-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2231246
• 关键词: adrenergic receptor; arrhythmia; atrium; autoradiography; calcium channel; cholinergic receptors; cytokine receptors; electrostimulus; enzyme inhibitors; hamsters; heart /lung bypass; heart contraction; heart pharmacology; human subject; interleukin 6; myocardial ischemia /hypoxia; myocardium; nitrates; nitrites; nitrogen oxides; papillary muscles; postoperative complications; receptor binding; sarcolemma

Myocardial depression remains a major cause of morbidity and mortality following cardiopulmonary bypass (CPB). Mechanisms contributing to this myocardial depression are ill-defined, but appear to involve an inflammatory component. The acute inflammatory response to injury results in the synthesis and release of cytokines by a variety of immune and non- immune cells. The P.I., Co-P.I. and Consultant were the first to propose the hypothesis that cytokine-stimulated production of nitric oxide (NO) contributed to post-CPB myocardial depression. They provided support for this hypothesis by demonstrating for the first time that: (l) cytokines depressed myocardial contractility in isolated hamster papillary muscles. (2) a specific cytokine (IL-6) was elevated in patients following CPB. (3) IL-6 depressed myocardial contractility in humans. (4) L-NMMA (known inhibitor of NO synthesis) blocked the negative inotropic effects of cytokines on the heart. (5) Myocardial NO synthesis increased in patients following CPB. Considerably more work needs to be done to definitely confirm or refute this hypothesis. However, it is clear that IL-6 and NO have the potential to modulate myocardial contractility in animals and humans. The mechanisms of action of these newly described endogenous regulators of myocardial contractility have yet to be fully elucidated. The specific aims for this project are: I. Identify the mechanism(s) responsible for the negative inotropic effect of IL-6 and NO on isolated hamster papillary muscles and human atrial pectinate muscles. II. Identify stimuli for myocardial NO production in isolated hamster papillary muscles and human atrial pectinate muscles. The results of these studies will provide important new insights into the mechanism of action of these newly identified endogenous regulators (IL-6; NO) of myocardial contractility.

心肌抑郁症仍然是发病率和死亡率的主要原因 遵循心肺旁路（CPB）。 有助于此的机制 心肌抑郁症的定义不明确，但似乎涉及 炎症成分。急性炎症反应对损伤结果 在各种免疫和非 - 免疫细胞。 P.I.，Co-P.I。和顾问是第一个提出建议的人 一氧化氮的产生（NO）的假设是 导致CPB后心肌抑郁症。他们提供了支持 该假设首次证明：（l）细胞因子 在孤立的仓鼠乳头肌肉中抑郁的心肌收缩性。 （2）CPB后患者的特定细胞因子（IL-6）升高。 （3）IL-6在人类中抑郁的心肌收缩性。 （4）L-NMMA（已知 无合成的抑制剂）阻止 心脏上的细胞因子。 （5）心肌无合成的患者增加 遵循CPB。绝对需要做更多的工作 确认或驳斥这一假设。 但是，很明显IL-6和没有 有可能调节动物的心肌收缩性和 人类。这些新描述的内生的作用机制 心肌收缩性的调节剂尚未完全阐明。 该项目的具体目的是： I.确定负责负性效应的机制 IL-6，隔离的仓鼠乳头肌肉和人类心房 固定肌肉。 ii。识别孤立仓鼠中心肌无产生的刺激 乳头状肌肉和人类心房肌肉。 这些研究的结果将为您提供重要的新见解 这些新鉴定的内源性调节剂的作用机理（IL-6； 否）心肌收缩。