The circulation in sleep in early life; critical phases in its functional development and neural control.

With the onset to air-breathing at birth, the newborn circulation and its neural control undergoes dramatic transformation from the fetal pattern, yet remains substantially distinct from and less mature than the adult circulation. The newborn (particularly the preterm newborn) faces a risk of hypoxic-ischemic injury to vital organs as its blood pressure is at lifetime minimum, and mal-adaptation of the respiratory system leading to hypoxaemia is common. The brain is particularly vulnerable as cerebral blood flow is also at a lifetime minimum at birth. Coincidentally, REM sleep time is at a maximum in the newborn period. Organ perfusion may be problematic in REM sleep as central autonomic commands can induce blood pressure variations, while protective respiratory, circulatory and arousal reflexes can be ineffective. Local regulation of blood flow becomes critical if reflex control becomes ineffective. However this too may be ineffective for ensuring cerebral perfusion in REM sleep as cerebral autoregulation is slow in this sleep state compared to NREM sleep and wakefulness. Key factors modifying the cerebral autoregulatory curve are vasoconstrictor effects arising from cerebral sympathetic nerve activity (SNA), and counterbalancing vasodilator actions of endothelial-derived factors including nitric oxide (NO). Both SNA vasoconstriction and NO vasodilatation are prominently expressed in the newborn, particularly during REM sleep. Recent work suggests that each of these counterbalancing factors may normally be protective of the newborn brain (SNA through limiting microcirculatory pressure, flow and distension; NO by promoting perfusion). With further growth of the newborn in the neonatal and infant periods there is significant adaptation of the circulation and its autonomic neural control. Notably, and perhaps significant for the pathogenesis of sudden infant death syndrome (SIDS), adaptation occurs in postnatal age-related phases, rather than progressively with age. Moreover, this period of development occurs along with the elaboration of sleep-wake cycles, specifically a decline in REM sleep and an increase in NREM sleep, with circulatory control differing significantly between the two sleep phases. This chapter will describe the postnatal development of cardiovascular function and its physiological control in sleep during these critical early life phases.