HYPOTHERMIC CIRCULATORY ARREST

这项将在新生狗身上进行的实验方案是设计的 阐明未成熟的大脑在多大程度上 在低温停循环期间保护免受缺血损伤。 这一系列研究的基本原理与公认的 先天性心脏病外科修复的探讨。特定的 目的包括：1)表征脑缺血的早期进化 因长时间低温停循环造成的损伤 并确定是否有迟发性神经元坏死 发生；2)调查保护 围产期脑缺血在低温循环中的损伤 除抑制氧化作用外或在抑制氧化作用之外的逮捕 新陈代谢；3)比较不完全和完全的程度 脑缺血对新生狗脑的保护(或有害) 在低温期间；4)确定其有益或有害的影响 低体温引起的高血糖对脑损伤的影响 新生犬的循环停止；以及5)确定保护性 特定治疗方式对缺血性脑损伤的影响 由新生犬体温过低引起的循环停顿。 实验程序将涉及通过以下方式诱导体温过低 麻醉、麻痹和人工呼吸中的表面冷却 新生狗温度升至20摄氏度，随后心脏骤停，最多120次 几分钟。之后，动物将被复苏，随后 他们将在特定的时间间隔接受神经病理分析 恢复。将确定局部氧化和能量代谢 低温停循环期间及术后的原位心脏复苏术 部分糖酵解和Krebs循环的浓度分析 中间体和高能磷酸盐化合物，使用酶， 荧光技术。31P磁共振波谱还将用于 按顺序测量大脑高能磷酸盐储量和 低温循环前后细胞内pH(Phi)的变化 逮捕。兴奋性和抑制性细胞外浓度 神经递质也将使用微透析技术进行测量。 最后，钙在大脑中的区域积聚 在低温循环停止后，将使用 [45Ca]-放射自显影。治疗干预措施可能会减少 低温停循环期间脑损伤的程度将 包括硫喷妥钠，黄嘌呤氧化酶抑制剂，氧嘌醇， 钙通道阻滞剂尼莫地平。额外的实验 协议包括“低流量”而不是“无流量”的诱导。 高血糖对体温过低影响的状态及测定 缺血性脑损伤。预计这些调查将 洞察脑出血的物理化学机制(S)和持续时间 低温对循环骤停的保护性影响。

This experimental protocol, to be conducted in newborn dogs, was designed to elucidate the manner and extent to which the immature brain is protected from ischemic damage during hypothermic circulatory arrest. The rationale for this line of research relates to the well-established approach to the surgical repair of congenital cardiac defects. Specific aims include: 1) to characterize the early evolution of ischemic brain damage which results from prolonged hypothermic circulatory arrest in newborn dogs and to determine whether or not a delayed neuronal necrosis occurs; 2) to investigate underlying mechanisms which protect the perinatal ischemic brain from injury during hypothermic circulatory arrest other than or in addition to a suppression of oxidative metabolism; 3) to compare the extent to which incomplete versus complete cerebral ischemia is protective (or deleterious) to newborn dog brain during hypothermia; 4) to ascertain the beneficial or deleterious effect of hyperglycemia on the brain damage which results from hypothermic circulatory arrest in newborn dogs; and 5) to determine the protective influence of specific therapeutic modalities on ischemic brain damage resulting from hypothermic circulatory arrest in newborn dogs. Experimental procedures will involve the induction of hypothermia by surface cooling in anesthetized, paralyzed and artifically ventilated newborn dogs to 20degreesC followed by cardiac arrest for up to 120 minutes. Thereafter, the animals will be resuscitated, following which they will undergo neuropathologic analysis at specific intervals of recovery. Regional oxidative and energy metabolism will be determined during and following hypothermic circulatory arrest by the in situ analysis of concentrations of selected glycolytic and Krebs cycle intermediates and high-energy phosphate compounds, using enzymatic, fluorometric techniques. 31P MR spectroscopy also will be used to measure sequentially cerebral high-energy phosphate reserves and intracellular pH (pHi) during and following hypothermic circulatory arrest. Extracellular concentrations of excitatory and inhibitory neurotransmitters also will be measured using a microdialysis technique. Lastly, the regional accumulation of calcium in brain during and following hypothermic circulatory arrest will be accomplished using [45Ca]-autoradiography. Therapeutic interventions to potentially reduce the extent of brain damage during hypothermic circulatory arrest will include thiopental sodium, the xanthine oxidase inhibitor, oxypurinol, and the calcium channel blocker, nimodipine. Additional experimental protocols include the induction of a 'low flow' rather that a 'no flow' state and the determination of the effect of hyperglycemia on hypothermic ischemic brain damage. It is anticipated that these investigations will provide insight into the physiochemical mechanism(s) and duration of the protective influence of hypothermia on circulatory arrest.