Sleep-dependent changes in the cerebral metabolic rate of oxygen consumption in newborn lambs

Abstract

Aim of this study was to determine whether REM sleep during early postnatal development is already characterised by a high cerebral oxygen uptake. In adults, cerebral blood flow (CBF) and cerebral metabolic rate of oxygen consumption (CMRO2) decrease from wakefulness to non-rapid-eye-movement (non-REM) sleep and return during REM sleep to values similar to those in wakefulness, especially in subcortical regions (cf. 1). No study addressed the issue of cerebral metabolism during REM sleep in newborn life, when REM sleep duration is at a lifetime maximum, while CBF is at a lifetime minimum. In this respect, a high CMRO2 during REM sleep could represent a metabolic challenge for newborns, and a situation of risk owing to the strong dependency of CBF dynamics on fluctuations in arterial blood pressure in this sleep state 2. Six Merino/Border-Leicester cross lambs 2–5 day old were anesthetised (halothane / N2O) and instrumented with electroencephalographic and electromyographic electrodes for determining the sleep state and with a transit-time ultrasonic flow probe around the superior sagittal sinus to measure CBF 3. Non-occlusive catheters were inserted into the carotid artery and in the superior sagittal sinus for blood sample withdrawal. Studies began at least 72 hours after surgery: each animal was recorded for 2–4 days, and every day blood samples (2 ml) were obtained simultaneously from the carotid artery and the superior sagittal sinus during uninterrupted epochs of wakefulness, non-REM sleep and REM sleep. Samples were collected in heparinised syringes and immediately analysed. The arterovenous difference in oxygen content, computed from the concentration and saturation of haemoglobin in the arterial and venous blood, was multiplied by CBF to yield estimates of CMRO2. Average data were obtained for each lamb and state. Data are presented as mean SEM. Cerebral oxygen arterovenous difference (mM) was 1.9 0.1 in wakefulness, 1.9 0.1 in non-REM sleep, and 1.7 0.1 in REM sleep. CBF (ml/min) was 21.2 2.1 in wakefulness, 18.5 2.3 in non-REM sleep, and 25.0 2.8 in REM sleep. The oxygen arterovenous difference correlated negatively with CBF (r = -0.44, p < 0.01, Pearson correlation computed on z-scores from 54 samples). Nonetheless, CMRO2 (micromol/min) was significantly higher (p < 0.05, Friedman test and Wilcoxon test) in REM sleep (42.4 4.7) and in wakefulness (39.8 5.0) than in non-REM sleep (34.6 4.3). Data thus demonstrate that in newborn lambs, cerebral oxygen uptake in REM sleep is higher than in non-REM sleep and similar to that in wakefulness. In lambs, the superior sagittal sinus mainly drains from the frontal and anterior parietal lobes 3. Therefore, these data suggest that in newborn life CMRO2 is high during REM sleep even in cortical regions, in which changes in CMRO2 among wake-sleep states are inconstant in adults 1.