EFFECTS OF SURGERY AND ASPHYXIA ON LEVELS OF NUCLEOSIDES, PURINE-BASES, AND LACTATE IN CEREBROSPINAL-FLUID OF FETAL LAMBS

During severe oxygen shortage, the fetal brain resorts to anaerobic me tabolism and ATP becomes catabolized. High levels of nucleosides, hypo xanthine, and xanthine (ATP catabolites) in cerebrospinal fluid (CSF) may therefore be associated with increased neonatal neurologic morbidi ty. In 22 fetal lambs (3 to 5 d after surgery, gestational age 123.5 /- 3.5 d), arterial oxygen content was progressively reduced to 35% of the baseline value with a balloon occluder around the maternal common internal iliac artery. This resulted in a 1-h period of asphyxia, lea ding to a pH of 7.02 +/- 0.03 and a base excess of -17.0 +/- 1.0 mM. M ortality was 50%. CSF was sampled from the spinal cistern and analyzed using HPLC. During reoxygenation, hypoxanthine and xanthine may serve as substrate for xanthine oxidase with concomitant production of oxyg en-derived free radicals, which may aggravate cerebral damage. The mai n difference between surviving and nonsurviving animals was the speed of increment of ATP catabolites in CSF: in the surviving group levels increased steadily, recovery values being significantly elevated compa red with asphyxia values, whereas in the nonsurviving group the rise w as rapid and levels during asphyxia did not differ significantly from levels during recovery. We conclude that 1) catheterization of the spi nal cistern leads to increased levels of CSF hypoxanthine, xanthine, a nd inosine, and 2) during fetal asphyxia, levels of these ATP cataboli tes and lactate in CSF increase. 3) Maximum levels are reached during the recovery period and are similar for surviving and nonsurviving ani mals, but during asphyxia CSF levels of hypoxanthine and lactate were higher in the nonsurviving fetuses. 4) The rate of increase of ATP cat abolites in CSF is higher in the nonsurviving animals and may therefor e be predictive for fetal death.