Effect of Perinatal Asphyxia on Systemic and Intracerebral pH and Glycolysis Metabolism in the Rat

Abstract

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°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.