ISCHEMIC AND CARDIOPLEGIC INJURY DURING CARDIAC SURGERY

心脏手术期间的缺血性和心脏停搏损伤

基本信息

批准号：
3343320
负责人：
JAMES E LOWE
金额：
$ 14.75万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1984
资助国家：
美国
起止时间：
1984-12-01 至 1987-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3343320
关键词：
acid base balance adenosine triphosphate carbon cardiotonic agents drug adverse effect electrochemistry electron microscopy heart metabolism heart surgery high performance liquid chromatography ion transport microelectrodes myocardial ischemia /hypoxia myocardium patient monitoring device potentiometry spectrometry temperature

项目摘要

The surgical correction of the majority of acquired and congenital cardiac defects requires that the myocardium undergo a period of global ischemia with the effects of this ischemia lessened by the infusion of cold, potassium-containing cardioplegia. Current cardioplegic solutions result in numerous undesirable side effects which include reversible and occasionally irreversible conduction system injury, cell swelling which affects contractility, reversible sarcolemmal phospholipid injury which affects cell volume regulation, intracellular enzyme denaturation as well as nucleoside washout upon reperfusion. Of fundamental importance to further improving intraoperative myocardial preservation techniques and the subsequent long term results achieved by cardiac operative procedures is a more detailed understanding of the basic pathogenesis of both reversible as well as irreversible injury during global ischemia. The planned research proposal has two interrelated specific aims designed to further our understanding of the basic pathogenesis of total ischemia, and to allow this process to be monitored in on-line fashion using new tissue microelectrodes capable of monitoring a variety of interstitial ionic and molecular events. Basic investigations of the pathogenesis of total ischemia will further investigate recent findings from our laboratory showing that during total ischemia, ultrastructural and metabolic evidence for irreversible injury appears first in the subendocardium and coincides closely with the eventual onset of ischemic contracture. Relevant to cardiac surgery is the finding that these changes occurred in a model system completely free of collateral flow and wall tension. Specific studies will be performed to determine why the metabolic rate of the subendocardium is increased and how to control this metabolic rate prior to a planned period of global ischemia. In order to develop an on-line means to determine the degree of ischemic injury occurring during cardiac operations, totally new tissue microelectrodes based on microfilamentous carbon rods will be developed which are capable of monitoring in on-line fashion tissue ionic and molecular fluxes which can be correlated with the progression of ischemic injury. The proposed microelectrode technology represents a totally new means to achieve this goal. Interstitial ionic and molecular fluxes (potassium, calcium, magnesium, hydrogen ions, NAD and hypoxanthine) occurring during varying degrees of reversible ischemia will be correlated with measureable markers such as high energy phosphate depletion and ultrastructural changes. These two interrelated projects rely heavily on basic investigative work but have definite clinical relevance. The research personnel involved in the planned work represent a unique combination of individuals with basic science investigative experience and the planned studies all relate to the clinical problem of improving surgical results.

大多数获得和先天心脏的手术校正缺陷要求心肌接受全球缺血时期由于感冒的输注而减少了这种缺血的作用，含有钾的心脏杂志。当前的心骨解决方案结果在许多不良副作用中，包括可逆和有时不可逆的传导系统损伤，细胞肿胀，这些肿胀影响收缩力，可逆的肌磷脂损伤还会影响细胞体积调节，细胞内酶变性作为再灌注后的核苷冲洗。对进一步改善术中心肌保存技术和随后通过心脏手术程序获得的长期长期结果是对两者的基本发病机理的更详细理解以及全球性缺血期间不可逆转的伤害。计划的研究提案具有两个相互关联的特定目标，旨在进一步了解总缺血的基本发病机理，并允许使用新组织以在线方式监控的这个过程微电极能够监测各种间隙离子和分子事件。总的发病机理的基本研究缺血将进一步调查我们实验室的最新发现表明在总缺血，超微结构和代谢证据期间对于不可逆的伤害，首先出现在心脏心脏和重合中与最终的缺血性缔约发作紧密相关。与心脏手术是这些变化发生在模型中的发现系统完全没有侧支流和墙张力。具体的将进行研究以确定为什么心内膜下增加以及如何控制这种代谢率计划的全球性缺血时期。为了开发在线手段确定心脏期间发生的缺血性损伤程度操作，基于微丝的全新组织微电极将开发能够在线监视的碳棒时尚组织离子和分子通量可以与缺血性损伤的进展。拟议的微电极技术代表了实现这一目标的全新手段。间质离子和分子通量（钾，钙，镁，氢离子，NAD和NAD和在不同程度的可逆缺血期间发生的低黄嘌呤）将会与可测量的标记（例如高能磷酸盐）相关消耗和超微结构变化。这两个相互关联的项目严重依赖基本的调查工作，但具有明确的临床关联。参与计划工作的研究人员代表与基础科学调查的个人的独特组合经验和计划的研究都与改善手术结果。