BRAIN PROTECTION DURING HYPOTHERMIC CIRCULATORY ARREST

低温停循环期间的脑保护

• 批准号: 3414969
• 负责人: JOHN F ALKSNE
• 金额: $ 28.23万
• 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/3414969
• 关键词: brain circulation; cerebral ischemia /hypoxia; chemoprevention; heart surgery; hippocampus; histopathology; hypoglycemia; induced hypothermia; neuroprotectants; 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.

尽管低温停循环在心脏手术中经常被使用 手术后，对大脑保护的充分性仍然存在疑问 以及允许的循环停止时间。一些外科医生在做手术 在幼儿身上使用了低温低流量而不是完全 循环停止，试图将脑损伤的风险降至最低， 尽管这从未被证明是有益的。同样，一些人 为老年人进行肺血栓手术的外科医生使用了 间歇性再灌流，试图安全地延长 逮捕，尽管没有证据表明这是有用的。在……里面 事实上，常温条件下的实验数据表明 反复再灌流或低血流可能是有害的，我们的初步研究 实验表明，低流量比滞留造成的伤害更大 同一时期。 关于脑保护的动物研究的一个主要缺点是难以 考察智力活动，例如记忆，这些活动显然是 对病人来说很重要。因此，我们选择使用形态上的 海马神经元神经损伤的标志，已知的是 对缺血最敏感的判断是反复再灌流还是低 流动对实验动物是有益的，也是有害的。 关于常温脑缺血的大量文献表明 葡萄糖耗竭可能会增加大脑对循环骤停的耐受性。 我们建议将低血糖和低温结合起来，试图延长 允许的循环停止时间。最近的动物实验 提示神经保护剂的存在可能会改善神经元 与全脑缺血相关的损伤。我们建议对动物进行预处理 接受低温停循环治疗，其中一些最有希望的 以确定它们是否会有神经保护作用 在我们的模型中的效果。