BRAIN PROTECTION DURING HYPOTHERMIC CIRCULATORY ARREST

低温停循环期间的脑保护

• 批准号: 3414968
• 负责人: JOHN F ALKSNE
• 金额: $ 27.05万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-08-01 至 1995-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3414968
• 关键词: brain circulation; cerebral ischemia /hypoxia; chemoprevention; heart surgery; hippocampus; histopathology; hypoglycemia; induced hypothermia; nonhuman therapy evaluation; reperfusion; swine

Although hypothermic circulatory arrest is used frequently in cardiac surgery, questions remain about the adequacy of brain protection provided and the duration of circulatory arrest allowable. Some surgeons operating on young children have utilized hypothermic low flow instead of complete circulatory arrest, in an attempt to minimize the risk of cerebral injury, although this has never been demonstrated beneficial. Similarly, some surgeons operating on the elderly for pulmonary thrombosis have used intermittent reperfusion in an attempt to safely extend the period of arrest, although there is no evidence to indicate this is useful. In actuality, experimental data at normothermic conditions suggests that repeated reperfusion or low flow could be injurious and our preliminary experiments indicate that low flow causes more injury than arrest for the same period. A major drawback to animal studies on brain protection is the difficulty in examining intellectual activities, such as memory, which are clearly important to patients. Therefore we have elected to use a morphological marker of neural damage in the hippocampal neurons which are known to be most sensitive to ischemia to determine if repeated re-perfusions or low flow are beneficial or detrimental to experimental animals. Extensive literature on normothermic cerebral ischemia suggests that glucose depletion may increase the brain tolerance to circulatory arrest. We propose to combine hypoglycemia and hypothermia in an attempt to extend the allowable period of circulatory arrest. Recent animal experiments suggest that neuroprotective agents exist which may ameliorate the neuronal injury associated with global ischemia. We propose to pretreat animals undergoing hypothermia circulatory arrest with some of the most promising of these agents to determine whether they will have a neuroprotective effect in our model.

虽然低温停循环在心脏病中经常使用， 手术，问题仍然是关于大脑保护的充分性， 以及循环停止的持续时间。 一些外科医生 对幼儿使用低温低流量，而不是完全 循环停止，以尽量减少脑损伤的风险， 尽管这从未被证明是有益的。 同样，一些 为老年人做肺血栓手术的外科医生 间歇性再灌注，试图安全地延长 逮捕，虽然没有证据表明这是有用的。 在 事实上，在常温条件下的实验数据表明， 反复再灌注或低流量可能是有害的，我们的初步研究表明， 实验表明，低流量造成更多的伤害比逮捕的 同期业绩 动物脑保护研究的一个主要缺点是很难 检查智力活动，如记忆，这显然是 对患者很重要。 因此，我们选择使用一种形态学 海马神经元中的神经损伤的标志物， 对局部缺血最敏感，以确定是否重复再灌注或低 流动对实验动物是有益的还是有害的。 大量关于常温脑缺血的文献表明， 葡萄糖消耗可增加脑对循环停止的耐受性。 我们建议将低血糖和低体温联合收割机治疗， 循环停止的允许时间 最近的动物实验 表明存在神经保护剂，可以改善神经元损伤 与全脑缺血相关的损伤。 我们建议对动物进行预处理 进行低温循环停止， 以确定它们是否具有神经保护作用， 在我们的模型中。