Sympathetic Withdrawal Augments Cerebral Blood Flow During Acute Hypercapnia in Sleeping Lambs

Abstract

Cerebral sympathetic activity constricts cerebral vessels and limits increases in cerebral blood flow (CBF), particularly in conditions such as hypercapnia which powerfully dilate cerebral vessels. As hypercapnia is common in sleep, especially in sleep disordered breathing, we tested the hypothesis that sympathetic innervation to the cerebral circulation attenuates the CBF increase that accompanies increases in PaCO2 in sleep, particularly in REM sleep when CBF is high. Newborn lambs (n = 5) were instrumented to record CBF, arterial pressure (AP) intracranial pressure (ICP), and sleep-wake state (quiet wakefulness (QW), NREM, and REM sleep). Cerebral vascular resistance was calculated as CVR = [AP-ICP]/CBF. Lambs were subjected to 60-sec tests of hypercapnia (FICO2 = 0.08) during spontaneous sleep-wake states before (intact) and after sympathectomy (bilateral superior cervical ganglionectomy). During hypercapnia in intact animals, CBF increased and CVR decreased in all sleep-wake states, with the greatest changes occurring in REM (CBF 39.3% +/- 6.1%, CVR -26.9% +/- 3.6%, P < 0.05). After sympathectomy, CBF increases (26.5% +/- 3.6%) and CVR decreases (-21.8% +/- 2.1%) during REM were less (P < 0.05). However the maximal CBF (27.8 +/- 4.2 mL/min) and minimum CVR (1.8 +/- 0.3 mm Hg/ min/mL) reached during hypercapnia were similar to intact values. Hypercapnia increases CBF in sleep and wakefulness, with the increase being greatest in REM. Sympathectomy increases baseline CBF, but decreases the response to hypercapnia. These findings suggest that cerebral sympathetic nerve activity is normally withdrawn during hypercapnia in REM sleep, augmenting the CBF response.