MYOCARDIAL CONTRACTILITY: NORMAL/PATHOLOGIC DEVELOPMENT

心肌收缩：正常/病理发展

• 批准号: 3448512
• 负责人: DAVID F TEITEL
• 金额: $ 4.36万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-04-01 至 1986-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3448512
• 关键词: beta adrenergic agent; congenital heart disorder; heart contraction; heart output disorder; heart pharmacology; hemodynamics; histogenesis; hypoxia neonatorum; intracardiac pressure; intracardiac volume; muscle stimulant; newborn animals; patent ductus arteriosus; propranolol; ventricular hypertrophy

I propose to study the developmental changes in myocardial contractility and inotropic reserve from the newborn period through the first month after birth in the chronically-instrumented lamb. Many studies have demonstrated high resting indices of ventricular performance in the newborn, but specific assessment of contractility has not been investigated. It will continue with the work that I have begun on the normal newborn, and will expand this work to include models of several forms of congenital heart disease: 1) chronic hypoxemia secondary to a right-to-left atrial shunt and right ventricular outflow tract obstruction; 2) left ventricular hypertrophy (produced in utero) secondary to LV outflow tract obstruction both with low and normal/high coronary artery perfusion pressure; and 3) LV volume overload secondary to a left-to-right shunt at the ductus arteriosus. To assess contractility, lambs will be operated upon within 3 days of birth. Via a left thoracotomy, catheters are placed in the ascending aorta, superior venna cava, pulmonary artery, and left atrium; a pressure-tip catheter in the apex of the LV; an echo transducer sutured to the LV epicardium to record LV wall thickness and minor axis dimension; and a flow transducer placed around the pulmonary artery. Following a greater than and equal 3 day recovery period, studies will be performed twice weekly to assess contractility at rest, and weekly under maximal Beta-adrenergic stimulation with isoproterenol and Beta-adrenergic blockade with propranolol. Each study consists of measuring LV pressure, dimension and wall thickness at 20 different levels of afterload during a graded phenylephrine infusion with vagal blockade using atropine to maintain a constant heart rate. At each afterload, "end-systolic" wall stress (WSt) and the cube of LV diameter (LVVI) are calculated. The slope of the WSt-LVVI relationship is the index of contractility used. With this information, I will be able to define myocardial contractility, its development and reserve, over the first month of life in normal lambs and those with simulated congenital heart disease. Since inotropic agents are a mainstay in the treatment of heart disease in the newborn, it is important to have this information in order to outline a more rational approach to their use in neonatal heart disease.

我建议研究心肌收缩性的发育变化 从新生时期到接下来的第一个月的肌力储备 长期蒙受的羔羊的出生。 许多研究表明 新生儿中心室表现的高静休息指标，但 尚未调查对收缩性的具体评估。 会 继续我开始对普通新生儿开始的工作，并将 扩展这项工作以包括几种先天性心脏的模型 疾病：1）继发于左心房分流的慢性低氧血症 和右心室流出道障碍； 2）左心室 肥大（在子宫内产生）继发于LV流出障碍物 低和正常/高冠状动脉灌注压力； 3）LV 辅导员从左到右分流的体积超载 动脉。 为了评估收缩力，羔羊将在3次内进行操作 出生日。 通过左胸腔切开术，将导管放在 上升主动脉，上venna cava，肺动脉和左心房；一个 LV的顶点中的压头导管；回声传感器缝合到 LV心外膜记录LV壁厚和次要轴尺寸；和 放置在肺动脉周围的流动传感器。 跟随更大 比和相等的3天恢复期，将进行两次研究 每周评估静止收缩性，每周在最大 β-肾上腺素能刺激以及异丙肾上腺素和β-肾上腺素能阻断 与普萘洛尔。 每项研究包括测量LV压力，尺寸 分级期间在20个不同级别的后负载下的壁厚 使用阿托品对迷走神经封锁输注苯肾上腺素以维持 持续的心率。 在每个后载时，“末期”左侧壁应力（WST） 计算LV直径（LVVI）的立方体。 坡 WST-LVI关系是使用的收缩率指数。 与此 信息，我将能够定义心肌收缩性 在正常羔羊和 那些患有先天性心脏病的人。 由于肌力剂是 在新生儿治疗心脏病的主要手段，它是 重要的是要概述更合理的信息 他们在新生儿心脏病中使用的方法。