Vannucci R C, Brucklacher R M, Vannucci S J
Department of Pediatrics (Pediatric Neurology), The Pennsylvania State University College of Medicine, The Milton S. Hershey Medical Center, Hershey 17033-0850, USA.
Pediatr Res. 1997 Jul;42(1):24-9. doi: 10.1203/00006450-199707000-00005.
We previously have demonstrated that hypocapnia aggravates and hypercapnia protects the immature rat from hypoxic-ischemic brain damage. To ascertain cerebral blood flow (CBF) and metabolic correlates, 7-d postnatal rats were subjected to hypoxia-ischemia during which they were rendered either hypo-(3.5 kPa), normo- (5.1 kPa), or hypercapnic (7.3 kPa) by the inhalation of either 0, 3, or 6% CO2, 8% O2, balance N2. CBF during hypoxia-ischemia was better preserved in the normo- and hypercapnic rat pups; these animals also exhibited a stimulation of cerebral glucose utilization. Brain glucose concentrations were higher and lactate lower in the normo- and hypercapnic animals, indicating that glucose was consumed oxidatively in these groups rather than by anaerobic glycolysis, as apparently occurred in the hypocapnic animals. ATP and phosphocreatine were better preserved in the normo- and hypercapnic rats compared with the hypocapnic animals. Cerebrospinal fluid glutamate, as a reflection of the brain extracellular fluid concentration, was lowest in the hypercapnic rats at 2 h of hypoxia-ischemia. The data indicate that during hypoxia-ischemia in the immature rat, CBF is better preserved during normo- and hypercapnia; the greater oxygen delivery promotes cerebral glucose utilization and oxidative metabolism for optimal maintenance of tissue high energy phosphate reserves. An inhibition of glutamate secretion into the synaptic cleft and its attenuation of N-methyl-D-aspartate receptor activation would further protect the hypercapnic animal from hypoxic-ischemic brain damage.
我们之前已经证明，低碳酸血症会加重未成熟大鼠的缺氧缺血性脑损伤，而高碳酸血症则具有保护作用。为了确定脑血流量（CBF）及其代谢相关性，对出生后7天的大鼠进行缺氧缺血处理，在此期间，通过吸入0%、3%或6%的二氧化碳、8%的氧气，其余为氮气，使它们分别处于低碳酸血症（3.5 kPa）、正常碳酸血症（5.1 kPa）或高碳酸血症（7.3 kPa）状态。在缺氧缺血期间，正常碳酸血症和高碳酸血症的幼鼠脑血流量得到了更好的维持；这些动物的脑葡萄糖利用率也有所提高。正常碳酸血症和高碳酸血症动物的脑葡萄糖浓度较高，乳酸浓度较低，这表明这些组中的葡萄糖是通过氧化消耗的，而不是像低碳酸血症动物那样通过无氧糖酵解消耗。与低碳酸血症动物相比，正常碳酸血症和高碳酸血症大鼠的三磷酸腺苷（ATP）和磷酸肌酸保存得更好。作为脑细胞外液浓度反映的脑脊液谷氨酸，在缺氧缺血2小时时，高碳酸血症大鼠中的浓度最低。数据表明，在未成熟大鼠缺氧缺血期间，正常碳酸血症和高碳酸血症时脑血流量能得到更好的维持；更多的氧气输送促进了脑葡萄糖利用和氧化代谢，以最佳维持组织高能磷酸盐储备。谷氨酸分泌到突触间隙的抑制及其对N-甲基-D-天冬氨酸受体激活的减弱将进一步保护高碳酸血症动物免受缺氧缺血性脑损伤。
