Effect of Cardioplegia and Cardiopulmonary Bypass on Coronary Microvascular Reactivity

摘要： 心脏手术，特别是涉及心脏停搏(CP)和体外循环(CPB)的手术，是相关的 随着血管运动调节的显著变化和随后的器官损伤，如神经认知障碍， 中风、肾和肠系膜衰竭、术后全身性低血压和冠状动脉痉挛。高血压 也与严重的自主神经功能障碍和血管运动调节有关，以及与 手术后的发病率和死亡率。这项拟议的研究的目标是确定 高血压控制良好与控制不良对血管信号改变的影响 转导和功能，并调查这些患者在治疗前后发生的变化 在体外循环和体外循环下接受心脏手术。具体地说，高血压相关的微血管差异 将重点研究1)肌源性张力，2)肾上腺素能和加压素诱导的功能 微血管信号和收缩，3)性别和年龄对肌源性的不同影响， 血管紧张素I和血管紧张素II，以及-肾上腺素能途径。这些目的将在井的微血管系统中进行检查- 控制和控制较差的高血压患者和年龄匹配的正常血压患者，使用体外 微血管成像。这项工作将通过一种详尽的方法来完成，使用分子和 细胞生物学技术检测与维持有关的基因和蛋白质的表达和激活 心脏手术后血管完整性和信号传递。这些研究的结果可能具有重要的意义 对心脏手术后高血压和其他患者康复的影响。

SUMMARY: Cardiac surgery, especially that involving cardioplegia (CP) and cardiopulmonary bypass (CPB), is associated with significant changes in vasomotor regulation and subsequent organ injury such as neurocognitive deficit, stroke, renal and mesenteric failure, post-operative systemic hypotension and coronary spasm. Hypertension is also associated with severe autonomic dysfunction and vasomotor regulation, as well as with increased morbidity and mortality after surgical procedures. The goal of the proposed research is to determine the effect of well-controlled and poorly controlled hypertension on alterations in vascular signal transduction and function and to investigate the changes that occur in these patients before and after undergoing heart surgery with CP and CPB. Specifically, hypertension-related differences in microvascular function will be investigated with specific focus on 1) myogenic tone, 2) -adrenergic and vasopressin-induced microvascular signaling and contraction, 3) and the differential effects of gender and aging on myogenic, angiotensin I and II, and -adrenergic pathway. These aims will be examined in the microvasculature of well- controlled and poorly controlled hypertensive and age-matched normotensive patients, using in vitro microvascular imaging. This work will be accomplished through an exhaustive approach using molecular and cellular biology techniques to examine gene and protein expression and activation involved in maintaining vascular integrity and signaling following cardiac surgery. The results of these studies may have significant implications regarding the recovery of hypertensive and other patients after cardiac surgery.