CARDIOPLEGIA EFFECT ON MYOCYTE VOLUME REGULATION

心麻痹对肌细胞体积调节的影响

• 批准号: 6012743
• 负责人: ROBERT G STRANGE
• 金额: $ 3.55万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-20 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6012743
• 关键词: cardiac myocytes; cell morphology; heart arrest; heart contraction; human tissue; hyperkalemias; myocardial ischemia /hypoxia; tissue /cell culture

Myocardial edema and cell swelling are common sequelae of cardiac surgery and have deleterious effects on postoperative cardiac physiology. Our principal hypothesis is that hyperkalemic cardioplegia itself, the most common method of myocardial protection, is responsible for this cell swelling. The objective of this proposal is to investigate the effect of cardioplegia on human myocyte volume regulation and contractility. Adult and neonatal human myocytes will be obtained during the course of routine cardiac surgery. Both atrial and ventricular myocytes will be isolated. Myocyte dimensions will be determined using high-resolution video microscopy coupled to a digital image analysis system. Each cell will serve as its own control. Experiments have been designed to test the hypothesis that standard hyperkalemic cardioplegia causes cell swelling. The mechanisms of cell swelling will be examined under both hypothermic and normothermic conditions. During hypothermia, our principle hypothesis is that the tonicity of the cardioplegia solution, that is the [K+]0X[Cl-]0 product of the cardioplegia, is the most important mechanism responsible for cell swelling. The role of the Na+/K+2Cl- co-transport system will be investigated under normothermic conditions. Moreover, comparisons will be drawn between adult and neonatal cells to identify differences in their cell volume regulation. We will than attempt to correlate changes in cell volume with cell contractility. Our goal is to delineate the mechanisms of cardioplegia-related cell swelling. Manipulation of cardioplegic solutions to prevent cell swelling may represent a new strategy to improve current techniques of myocardial protection.

心肌水肿和细胞肿胀是心脏手术的常见后遗症，对术后心脏生理学有害。 我们的主要假设是，高钾血症心脏病本身是心肌保护的最常见方法，是该细胞肿胀的原因。 该提案的目的是研究心脏丘脑对人肌细胞体积调节和收缩力的影响。 在常规心脏手术过程中，将获得成年和新生儿人肌细胞。 心房和心室心肌细胞都将分离出来。 心肌尺寸将使用高分辨率视频显微镜与数字图像分析系统结合来确定。 每个单元将作为自己的控制。实验旨在检验以下假设：标准高钾血症患者会导致细胞肿胀。 细胞肿胀的机制将在低温和正常温度条件下进行检查。 在体温过低期间，我们的原理假设是心脏杂草溶液（即心脏杂草质的[k+] 0x [cl-] 0产物）的补体是负责细胞肿胀的最重要机制。 Na+/K+2Cl-共同转移系统的作用将在正常温度条件下进行研究。 此外，将在成人和新生细胞之间进行比较，以鉴定其细胞体积调节的差异。 我们将尝试将细胞体积变化与细胞收缩性相关联。 我们的目标是描述与心脏双毛相关的细胞肿胀的机制。 对防止细胞肿胀的心骨解决方案的操纵可能代表了改善心肌保护技术技术的新策略。