During severe oxygen shortage, the fetal brain resorts to anaerobic metabolism and ATP becomes catabolized. High levels of nucleosides, hypoxanthine, and xanthine (ATP catabolites) in cerebrospinal fluid (CSF) may therefore be associated with increased neonatal neurologic morbidity. In 22 fetal lambs (3 to 5 d after surgery, gestational age 123.5 r 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, leading to a pH of 7.02 ? 0.03 and a base excess of -17.0 ? 1.0 mM. Mortality 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 oxygen-derived free radicals, which may aggravate cerebral damage. The main 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 compared with asphyxia values, whereas in the nonsurviving group the rise was rapid and levels during asphyxia did not differ significantly from levels during recovery. We conclude that I ) catheterization of the spinal cistern leads to increased levels of CSF hypoxanthine, xanthine, and inosine, and 2) during fetal asphyxia, levels of these ATP catabolites and lactate in CSF increase. 3 ) Maximum levels are reached during the recovery period and are similar for surviving and nonsurviving animals, but during asphyxia CSF levels of hypoxanthine and lactate were higher in the nonsurviving fetuses. 4) The rate of increase of ATP catabolites in CSF is higher in the nonsurviving animals and may therefore be predictive for fetal death. (1) and preferential streaming of well-oxygenated blood in the heart (2), the fetal cerebrum is provided with as much oxygen as possible. During severe or sustained oxygen shortage, however, the brain too resorts to anaerobic metabolism. Lack of oxygen impairs mitochondria1 functioning, leading to energy shortage (3); ATP becomes degraded to AMP and, after dephosphorylation, further to adenosine, inosine, and hypoxanthine. Serum levels of hypoxanthine are considered a sensitive indicator of the hypoxic insult (4). Moreover, formation of hypoxanthine and xanthine may aggravate outcome after such an insult, because during reoxygenation hypoxanthine and xan-
