Effect of intermittent umbilical cord occlusion on fetal respiratory activity and brain adenosine in late-gestation sheep

Abstract

It was hypothesized that intermittent umbilical cord occlusion (UCO) would inhibit ovine fetal breathing movements (FBM) in association with increased cerebral adenosine levels. To test this hypothesis, on two successive days during late gestation (133–134 days; term = 146 days), microdialysis samples were collected from the brains of 10 chronically instrumented fetal sheep during 2-h periods of complete UCO induced every 30 min (Day 1: 2-min UCOs; Day 2: 4-min UCOs). Control fetuses (n = 10) underwent no UCO. Tracheal pressure was measured throughout. This regimen resulted in a decrease in fetal arterial PO₂ (PaO₂) during each UCO to 7.3 0.8 mmHg (P<0.01; Day 1) and 8.4 1.1 mmHg (P<0.01; Day 2). Throughout each UCO period, fetal arterial pH (pHa) decreased to 7.28 0.02 (P<0.01; Day 1) and 7.11 0.07 (P<0.01; Day 2). The hourly incidence of FBM decreased significantly only on Day 2, from 38.6 4.1% to 4.1 1.6% (P<0.01). The frequency of deep isolated inspiratory efforts increased from 4.7 2.0 h^–1 to 17.6 6.1 h^–1 (P<0.05; Day 1) and from 2.2 0.9 h^–1 to 33.6 4 h^–1 (P<0.01; Day 2). The amplitude of both FBM and deep isolated inspiratory efforts increased during the UCO periods on both days. The concentration of cerebral extracellular fluid (ECF) adenosine during UCO increased by 219 215% (P<0.05; Day 1) and 172 107% (P<0.05; Day 2) over the baseline periods. In conclusion, the severity of the inhibitory effect of repeated UCO on FBM depends, in part, on the length of the occlusions. The inhibition of FBM during intermittent UCO may be mediated by the increase in ECF adenosine in the fetal brain. Furthermore, FBM and deep isolated inspiratory efforts appear to be regulated by different mechanisms.