THE NEONATAL HEART AND CARDIOPULMONARY BYPASS

描述（改编自申请人的摘要）：本提案的目的是 以确定补体激活的作用，这发生在 体外循环，对体外循环后心肺功能的影响。主要研究者有 利用新生仔猪模型与心肺转流和低温， 证明存在多种补体途径的显著激活 导致对心肌和肺的直接损伤。他们将首先确定 阻断补体激活的各种途径对 体外循环术后心肺功能的恢复，以及第二部分 这些研究将使用新生儿进行类似的机制分析， 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 激活蛋白水解活性对收缩蛋白的影响。在 最后阶段，他们将利用重建战略，以取代 有缺陷的肌钙蛋白，以确定它们是否可以恢复心脏功能 通过这种方法。最终，目标将是诱导这些基因的表达， 促进心脏恢复的蛋白质。

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.