BRIEF REPEATED UMBILICAL-CORD OCCLUSIONS CAUSE SUSTAINED CYTOTOXIC CEREBRAL EDEMA AND FOCAL INFARCTS IN NEAR-TERM FETAL LAMBS

The aim of this study was to determine whether asphyxia induced by cli nically relevant, brief repetitive umbilical cord occlusions is associ ated with cerebral compromise. Chronically instrumented fetal lambs we re studied at 126.5 +/- 2.8 d of gestation (mean +/- SD, term 147 d). Occlusions were performed 1 out of every 2.5 min (group I, n = 7), 2 o ut of every 5 min (group II, n = 9), or not at all (shams, group III, n = 5), and discontinued at a predetermined threshold of severe or per sistent hypotension. After 58 +/- 8 and 24 +/- 2 occlusions, in groups I and II, respectively, the pH was 6.83 +/- 0.09, Pco(2) 9.52 +/- 1.4 kPa, base excess -23.5 +/- 3.7 mM, and lactate 14.1 +/- 1.6 mM. Two f etuses (out of group II) did not recover from the final occlusion. Ong oing asphyxia was associated with progressive suppression of the EEG, which occurred faster and with more epileptiform and spike activity in group II. Cortical impedance remained elevated for 15.0 +/- 4.0 and 1 1.5 +/- 4.4 h, for groups I and II, respectively (NS). Focal infarcts occurred in the parasagittal cortex, thalamus, and cerebellum, in 6 ou t of 14 surviving asphyxiated fetuses. Mild selective neuronal loss wa s observed in these regions in 13 out of 14 fetuses, Infarction was as sociated with a longer period of blood pressure below baseline levels, with more epileptiform activity, and with slower normalization of the EEG. In a paradigm mimicking birth asphyxia, histologic damage simila r to that observed clinically was found. The results suggest that brie f repeated insults interact, leading to cardiac compromise and cumulat ive cell membrane damage in the fetal cerebrum.