Generation of periventricular leukomalacia by repeated umbilical cord occlusion in near-term fetal sheep and its possible pathogenetical mechanisms

Periventricular leukomalacia (PVL) is a major cause of cerebral palsy. Howe ver, pathogenetic mechanisms of PVL have not been fully understood. Althoug h it has been postulated that umbilical cord compression is related to the development of PVL, no animal experiments clearly demonstrated an associati on of umbilical cord occlusion with 'periventricular' white matter lesions. The purpose of this study is to determine whether umbilical cord occlusion s could produce periventricular white matter lesions in feta I sheep and to examine how changes in fetal cardiovascular and metabolic variables are re lated to the induction of brain damage. Fourteen near-term fetal sheep unde rwent umbilical cord occlusion (3-min total cord occlusions 5 times at 5-mi n intervals). Dissections performed 24 h after cord occlusion revealed that periventricular white matter lesions were produced in 7 out of 14 sheep fe tuses. According to the pattern of brain damage, we classified the fetal sh eep into th ree groups: 5 fetuses with dominant lesions in the periventricu lar white matter (group 1), 4 fetuses with brain lesions in the cerebral co rtex and thalamus (group II) and 5 fetuses with no or minimal brain lesions (group III). Group I showed higher blood pressure and higher plasma lipid peroxide levels before cord occlusion compared to the other groups, while g roup II showed systemic hypotension during cord occlusion. No significant d ifferences in changes in pH, PaCO2, PaO2 and heart rate were found between the th ree groups. It is speculated that PVL might be produced by an associ ation of preexisting chronic circulatory instability with an acute episode of severe repetitive cord occlusion. Copyright (C) 2001 S. Karger AG, Basel .