Fetal cerebral responses to ventilation and oxygenation in utero

Abstract

Previous studies have shown that cerebral oxygen consumption (CMRO2) increases by nearly 50% at birth. The perinatal factors responsible for this increase are unknown; however, one possibility is that fetal CMRO2 is constrained by the normal intrauterine arterial PO2 (PaO2) of approximately 20 mmHg. We investigated this possibility in seven near-term chronically instrumented fetal sheep (131-138 days gestation) in which we inserted vascular catheters and an endotracheal tube. After 1-3 days recovery, we measured cerebral blood flow (CBF) with radiolabeled microspheres and calculated CMRO2. Measurements were made in utero under three conditions for each fetus: 1) nonventilated control; 2) ventilation with 3% O2-5% CO2-92% N2; and 3) ventilation with an inspired oxygen concentration sufficient to raise fetal PaO2 to normal newborn levels (mean 73 mmHg). A calf lung surfactant extract (CLSE) was instilled into the endotracheal tube of the fetus before ventilation to ensure adequate levels of alveolar surfactant and to maintain stable pH and arterial PCO2. The results showed that increasing fetal arterial PO2 to postnatal levels did not consistently increase CMRO2. CBF decreased as arterial O2 content (CaO2) rose, with an inverse hyperbolic response similar to that previously found to relate CBF to CaO2 during fetal hypoxic hypoxia. This indicates that the normally low intrauterine PaO2 does not intrinsically limit CMRO2 and implies that the rapid increase in CMRO2 at birth reflects the activation of specific cellular and physiological processes at (or near) this unique developmental event.

Effect of Mild Hypothermia and Hypoxia on Blood Flow and Oxygen Consumption of the Fetal Sheep Brain

“…This finding supports the previously suggested idea that, under normal conditions, the diffusion of oxygen is not a limiting factor in cerebral oxygen consumption despite the relatively small driving pressure for oxygen diffusion between the fetal capillaries and brain tissue (7). The present study also is in agreement with previous work showing that the fetus responds to increased arterial oxygen tensions by decreasing cerebral blood flow rather than increasing cerebral oxygen consumption as would be expected if cerebral oxygen consumption were normally limited by oxygen diffusion (15).…”

Protective Ventilation of Preterm Lambs Exposed to Acute Chorioamnionitis Does Not Reduce Ventilation-Induced Lung or Brain Injury

“…Most preterm infants <30 weeks have episodes of impaired autoregulation [43], and a link between chorioamnionitis and impaired autoregulation has been suggested in infants [44], [45] and sheep [21], although this has not been extensively studied. In this study, ventilated lambs maintained constant cerebral blood volume during the ventilation period suggesting cerebral vasoparalysis; normally there is a gradual decline in cerebral blood volume after birth as oxygen delivery increases [46]. Clinically, preterm infants exposed to chorioamnionitis have reduced variability in oxygenated and deoxygenated haemoglobin in brain tissue, with infants exhibiting the lowest variation having the most severe intraventricular haemorrhage and periventricular leukomalacia [47].…”

Initiation of Resuscitation with High Tidal Volumes Causes Cerebral Hemodynamic Disturbance, Brain Inflammation and Injury in Preterm Lambs

“…The normal postnatal reduction in cerebral blood volume and cerebral blood flow is a well-established and described phenomenon in both animals [35] and humans at term [36], [37] and preterm [38]. It results from the normal postnatal increase in oxygen content and demonstrates the importance of oxygen delivery in regulating CBF [39]. In contrast, lambs subjected to High V T resuscitation failed to display a decrease in CBV, despite similar or higher (first 15 min) blood oxygenation levels, suggesting that the normal postnatal adaptation of the cerebral circulation has been altered in these lambs.…”