Physiological Studies During Sleep

Abstract

The unifying theme throughout this Doctorate of Science thesis is the development, refinement and utilisation of physiological recordings during sleep to study, initially in animal models then subsequently in infants and children. This thesis incorporates 143 research publications from studies commencing in the early 1980’s up to 2015. Early studies for my PhD (part-time 1982-1988) investigated arousal responses from sleep to hypotensive and hypertensive stimuli in newborn lambs to ascertain the underlying mechanisms of Sudden Infant Death Syndrome. My postdoctoral studies at the Microsurgery Research Centre, St Vincent’s Hospital (1988-1991) focused on developing a sheep model of inutero wound healing while those at the Howard Florey Institute of Medical Research, University of Melbourne (1991-1992) were focused on kidney function in the ovine fetus. From 1995, when I returned to the Department of Paediatrics at Monash University, my studies have been in human infants investigating how the risk factors for Sudden Infant Death Syndrome affect infant physiology and cardiovascular, behavioural and neurocognitive effects of sleep disordered breathing in children. The work is divided into 7 chapters with papers listed chronologically in each chapter. Chapter 1 (Publications 1-8) presents studies conducted during my part time PhD candidature and position as a Research Officer at the Centre for Early Human Development (later to become the Ritchie Centre for Baby Health Research and now the Ritchie Centre), Monash University. The studies for my PhD investigated arousal responses to hypotension and hypertension in the newborn lamb. A failure of arousal responses is thought to be a cause of the Sudden Infant Death Syndrome (SIDS). These studies involved developing techniques to instrument fetal lambs late in gestation so that they could be studied immediately after birth. The studies showed that both hypotension and hypertension were arousing stimuli and responses were sleep state dependent, with lambs taking longer to arouse from active sleep compared to quiet sleep. Sinoaortic denervation showed that these responses were mediated via the arterial baroreceptors. Other studies included in this chapter examined the initiation of breathing at birth which I participated in in my role as Research Officer. These studies showed that fetal breathing movements decreased 2-3 days before birth and were absent during labour. Chapter 2 (Publications 9-11) presents studies in which I developed a large animal model for inutero fetal repair to examine wound healing. These studies were conducted during my postdoctoral position at the Microsurgery Research Centre at St Vincent’s Hospital, Melbourne. The studies found that the cellular inflammatory response to wound healing was less than in the newborn lamb, but scar tissue was still formed from as early as 75 days of gestation. Chapter 3 (Publications 12-13) presents studies of the development of kidney function in fetal sheep carried out during a one year part-time postdoctoral position at the Howard Florey Institute of Medical Research. [...]