Analysis of cerebral blood flow and oxygen metabolism under mild brain hypothermia

为探讨亚低温治疗对脑缺血的影响及其生理机制，在常温（-37ºC）和低温（-33.5ºC）条件下，测定沙鼠双侧缺血30 min时脑血流量和脑氧张力的变化。双侧颈内动脉闭塞引起大鼠脑缺血。分别用激光多普勒血流法和极谱氧饱和度法测定脑血流量（CBF）和组织氧张力（PTO_2）。在ICA阻断开始后-15秒内CBF迅速下降到激光多普勒流量计的背景水平，而PTO_2下降速度较慢。与CBF相比，to_2恢复到缺血前水平的速度较慢。脑缺血恢复过程中PTO_2/CBF比值曲线显示，在轻度低温条件下，脑组织氧代谢得到较好的维持。在此基础上，我们开发了一种新的系统，利用氧猝灭荧光膜技术，在氧敏感膜上显示大鼠肠系膜微循环中PO_2在体内的分布，从而显示皮层表面氧张力的变化。这种可视化技术被认为是研究缺血脑中氧转运和代谢的一种新的有效工具。此外，为了进一步探讨亚低温对脑氧代谢的影响，我们评估了流变学（微循环血液粘度）和物理因素（粘性模型溶液中氧的扩散系数）作为温度的函数。

To assess the impact and physiological mechanisms of mild hypothermic therapy for brain ischemia, the changes in cerebral blood flow and cerebral oxygen tension during and after bilateral ischemia were measured for 30 min. in gerbil rats under normothermic (-37ﾟC) and hypothermic (-33.5ﾟC) conditions. Brain ischemia was induced by bilateral occlusion of internal carotid arteries of the animals. Cerebral blood flow (CBF) and tissue oxygen tension (PTO_2) were measured by Laser-Doppler flowmetry and by polarographic oxymetry, respectively. CBF fell rapidly to background level of the Laser-Doppler flow meter by -15 sec after the start of ICA occlusion, but PTO_2 showed slower reduction. Also, the restoration of PTO_2 to pre-ischemic level was retarded than that of CBF.The obtained profile of PTO_2/CBF ratio during recovery from ischemia showed that the oxygen metabolism in the brain was better maintained in the mildly hypothermic condition.Together with these studies, a new system was developed to visualize the changes in oxygen tension on the cortical surface by using an oxygen-quenching fluorescent membrane technique, recently developed by us for in vivo visualization of PO_2 distribution in the rat mesenteric microcirculation, as epifluorescent microscopic patterns on the oxygen-sensitive membrane. This visualization technique was considered to be a novel potent tool for the study of oxygen transport and metabolism in the ischemic brain.Also, to further explore the effect of mild hypothermia on cerebral oxygen metabolism, rheological (blood viscosity in microcirculation) and physical (diffusion coefficient of oxygen in viscous model solutions) factors were assessed as a function of temperature.