Engidawork E, Chen Y, Dell'Anna E, Goiny M, Lubec G, Ungerstedt U, Andersson K, Herrera-Marschitz M
Department of Physiology & Pharmacology, Karolinska Institute, Stockholm, Sweden.
Exp Neurol. 1997 Jun;145(2 Pt 1):390-6. doi: 10.1006/exnr.1997.6482.
The effects of perinatal asphyxia on systemic and brain pH and glycolysis metabolism were studied in the rat. Perinatal asphyxia was induced by immersing pup-containing uterus horns, obtained by cesarean section from rats within the last day of gestation, in a water bath at 37 degrees C for various periods of time (0-23 min). Subcutaneous levels of pyruvate (Pyr), lactate (Lact), glutamate (Glu), and aspartate (Asp) were monitored with microdialysis 40-80 min after delivery. In parallel experiments, the pups were sacrificed 40 min after delivery and the heart and brain were removed for measuring pH. Brain (striatum) Pyr, Lact, Glu, and Asp levels were also analyzed. A decrease in the rate of survival was first observed following asphyctic periods longer than 16 min, and no survival could be observed after 22 min of asphyxia. In control (cesarean-delivered) pups, heart and brain pH were 7.36 +/- 0.01 (N = 8) and 7.30 +/- 0.01 (N = 8), respectively. Significant decreases in pH were first observed following 5-6 and 10-11 min of asphyxia, in heart and brain, respectively. In both regions pH decreased along with the length of asphyxia, but a decrease below 7 was only observed in the brain, following asphyctic periods longer than 16 min. A significant increase in subcutaneous Lact levels was first observed following 2-3 min of asphyxia, with a maximum after 20-21 min of asphyxia. In the brain, the increase in Lact levels was delayed compared to that observed in subcutaneous tissue. Pyr and Asp levels increased in subcutaneous tissue following perinatal asphyxia and decreased in brain tissue following > 15 min of asphyxia. Glu levels were increased subcutaneously by moderate (5-16 min) asphyctic periods, but, in the brain, were only transiently increased by 10-11 min of asphyxia. Thus, changes in systemic pH, glycolysis, and excitatory amino acid metabolism are observed following shorter asphyctic periods than are changes in the brain. In particular, increases in subcutaneous Lact levels precede: (i) a decrease in brain pH, (ii) an increase in brain Lact levels, (iii) a decrease in the rate of survival, and, probably, (iv) brain damage. It is suggested that monitoring Lact levels by subcutaneous microdialysis is a useful method for predicting the outcome produced by hypoxic-ischemic insults.
在大鼠中研究了围产期窒息对全身及脑pH值和糖酵解代谢的影响。通过将妊娠最后一天剖宫产获得的含幼崽子宫角在37℃水浴中浸泡不同时间（0 - 23分钟）来诱导围产期窒息。分娩后40 - 80分钟用微透析监测皮下丙酮酸（Pyr）、乳酸（Lact）、谷氨酸（Glu）和天冬氨酸（Asp）水平。在平行实验中，分娩后40分钟处死幼崽，取出心脏和脑用于测量pH值。还分析了脑（纹状体）中Pyr、Lact、Glu和Asp水平。窒息时间超过16分钟后首次观察到存活率下降，窒息22分钟后未观察到存活情况。在对照（剖宫产）幼崽中，心脏和脑的pH值分别为7.36±0.01（N = 8）和7.30±0.01（N = 8）。分别在窒息5 - 6分钟和10 - 11分钟后首次观察到心脏和脑的pH值显著下降。在两个区域，pH值均随窒息时间延长而降低，但仅在窒息时间超过16分钟后，脑内pH值才降至7以下。窒息2 - 3分钟后首次观察到皮下Lact水平显著升高，在窒息20 - 21分钟后达到最高。在脑中，Lact水平的升高比皮下组织中观察到的延迟。围产期窒息后皮下组织中Pyr和Asp水平升高，窒息超过15分钟后脑组织中Pyr和Asp水平降低。中度（5 - 16分钟）窒息期使皮下Glu水平升高，但在脑中，仅在窒息10 - 11分钟时Glu水平短暂升高。因此，与脑内变化相比，在较短的窒息期后即可观察到全身pH值、糖酵解及兴奋性氨基酸代谢的变化。特别是，皮下Lact水平升高先于：（i）脑pH值降低，（ii）脑Lact水平升高，（iii）存活率下降，并且可能（iv）脑损伤。提示通过皮下微透析监测Lact水平是预测缺氧缺血性损伤所致结局的一种有用方法。
