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，测定了大鼠双侧脑缺血30min后脑血流量和脑氧分压的变化。常温(-37ﾟC)和低温(-33.5ﾟC)条件下的沙土鼠。采用双侧颈内动脉结扎诱导脑缺血模型。用激光多普勒血流仪和极谱血氧仪分别测定脑血流量(CBF)和组织氧分压(PtO2)。颈内动脉阻断后-15s，CBF迅速下降至激光多普勒血流仪的背景水平，但PtO2下降较慢。PTO_2/CBF比值的变化表明，在轻度低温条件下，脑组织的氧代谢得到了较好的维持。结合这些研究，我们开发了一种新的系统，利用我们最近开发的氧猝灭荧光膜技术来显示大鼠肠系膜微循环中PO_2的分布，作为氧敏感膜上的超荧光显微镜图像。这一可视化技术被认为是研究缺血脑组织氧运输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，我们评估了血液流变学(微循环中的血液粘度)和物理(氧气在粘性模型溶液中的扩散系数)因素随温度的变化。

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.