NERVE BLOOD FLOW IN NORMAL AND ISCHEMIC PERIPHERAL NERVE

描述(调查人员摘要)：我们将继续研究 神经缺血。基于神经保护的初步结果。 低温、高压氧(HBO)和自由基清除剂， 我们将评估这三种周围神经保护策略 由缺血性纤维变性(IFD)引起。假设是这样的 低温神经保护的发生是因为神经具有强大的能量 储存和代谢率低，是能够在厌氧条件下生存的 新陈代谢，只要它的能量需求进一步减少 因为体温过低。第一个具体目标是定义治疗性的 低温神经保护的窗口，就程度和 体温过低的持续时间和最大耐受延迟。第二个目标 是为了评估这种保护的机制。为了实现这一目标，我们 将进行以下5项研究。我们将评估(1)效果 低温对神经能量代谢的影响；(2)对葡萄糖的影响 利用率(14C-脱氧葡萄糖)。(3)我们将评估是否增强了 葡萄糖转运(二氢磷脂酸)或(4)增加神经内分泌 葡萄糖，会增强神经保护作用。(5)最后，我们将测试 认为高血糖会增强而不是降低的观念 神经保护，因为大的神经内神经间隙充分缓冲 神经乳酸或质子的变化。第三个目标是评估 高压氧的神经保护作用。第四个目标是评估 改变氧化应激对神经保护的影响。我们的方法 与神经特别相关，我们将使用可以 用于临床。我们会用来抑制花生四烯酸的级联 消炎痛。由于以下原因，将给予还原型谷胱甘肽 神经中谷胱甘肽及其酶的活性很低。最后，我们 将使用普罗布考、α-生育酚和硫辛酸，三位亲脂的阿姨 它可以阻止脂质过氧化，并已用于临床。第五个目标 继续我们对神经血管调节的研究。我们会研究 加压素、神经肽Y和西洛他唑(血管扩张剂和 磷酸二酯酶抑制剂对神经血流量的影响。

DESCRIPTION (Investigator's Abstract): We will continue our studies on nerve ischemia. Based on preliminary results of neuroprotection by. hypothermia, hyperbaric oxygenation (HBO), and free radical scavengers, we will evaluate these 3 strategies, of peripheral nerve neuroprotection from ischemic fiber degeneration (IFD). The hypothesis is that hypothermic neuroprotection occurs because nerve, with its large energy stores and low metabolic rate, is able to survive on.anaerobic metabolism, provided that its energy requirements are further reduced by hypothermia. The first specific aim is to define the therapeutic window of hypothermic neuroprotection, in terms of the degree and duration of hypothermia, and the maximal tolerated delay. The second aim is to evaluate the mechanism of this protect,ion. To achieve this, we will undertake the following 5 studies. We will evaluate (1) the effect of hypothermia on nerve energy metabolism, and (2) on glucose utilization ( 14 C-deoxyglucose). (3) We will evaluate if enhancing glucose transport (dihyarolipoic acid) or (4) increasing endoneuriaI glucose, will enhance neuroprotection. (5) Finally, we will test the notion that hyperglycemia will enhance rather than reduce neuroprotection because the large endoneurial space adequately buffers changes in nerve lactate or protons. The third aim is to evaluate the efficacy of HBO as neuroprotection. The fourth aim is to evaluate the effects of altering oxidative stress on neuroprotection. Our approach is specifically relevant to nerve, and we will use agents that can be used clinically. We will inhibit the arachidonic acid cascade with indomethacin. Reduced glutathione will be administered because of nerves very low activity of glutathione and its enzymes. Finally, we will use probucol, a-tocopherol, and lipoic acid, three lipophilic aunts that stop lipid peroxidation and has been used clinically. The fifth aim is to continue our studies of nerve vasoregulation. We will study vasopressin, neuropeptide Y, and cilostazol (vasodilator and phosphodiesterase inhibitor on nerve blood flow.