THE NEONATAL HEART AND CARDIOPULMONARY BYPASS

描述(改编自申请者摘要)：本提案的目的是 为了确定补体激活的作用，补体激活发生在 体外循环，对体外循环后心肺功能的影响。少年派有 利用新生仔猪体外循环低温模型 证明存在多种补体途径的显著激活 导致心肌和肺的直接损伤。他们将首先确定 阻断补体激活的多条途径对大鼠血管紧张素转换酶的影响 心肺转流后心肺功能恢复情况 这些研究他们将使用一个新生儿进行类似的机械分析 心肌细胞模型。在随后的研究中，他们将确定 补体激活对心肌肌丝结构和功能的影响 蛋白分解活性的激活对收缩蛋白的影响。在……里面 最后阶段，他们将利用重组战略来取代 肌钙蛋白缺陷以确定它们是否能恢复心脏功能 通过这种方法。最终，我们的目标将是诱导这些基因的表达 改善心脏恢复的蛋白质。

DESCRIPTION (Adapted from Applicant's Abstract):The aims of this proposal are to determine the role of complement activation, which occurs during cardiopulmonary bypass, on heart and lung function after bypass. The PI has utilized a neonatal piglet model with cardiopulmonary bypass and hypothermia to demonstrate that there is significant activation of various complement pathways resulting in direct injury to myocardium and lungs. They will first determine the effects of blocking the various pathways of complement activation on recovery of heart and lung function after bypass, and in the second part of these studies they will perform similar mechanistic analysis using a neonatal cardiac myocyte model. In subsequent studies they will determine the role of complement activation on cardiac myofilament structure and function and the effects of activation of proteolytic activity on the contractile proteins. In the final phase they will utilize a reconstitution strategy to replace defective troponin proteins to determine if they can restore cardiac function by this approach. Ultimately, the goal would be to induce expression of these proteins to improve cardiac recovery.