Abstract
Early exposure to the extrauterine environment (<37 weeks’ gestation) and the (mal)adaptations that occur during the transitional period result in alterations to the preterm infants’ macro- and micro-physiological state. These physiological adaptations that increase survival in the short term, place ex-preterms on a trajectory of lifelong dysfunction and later-life decompensation. While capable of compensating at rest, these dysfunctional traits become apparent under duress, such that ex-preterm adolescents and adults have reduced cardiovascular capacity to tolerate physiological stressors, and poorer recovery following. This has grave implications for their response to thermal stress, a factor that will continue to become an increasingly pressing concern in the face of climate change. As such, this thesis explored the functional maturation of the ex-preterm cardiovascular system to childhood, at which point dysfunctional traits begin to manifest, and explored cardiovascular reactivity using both local and whole-body thermal stress.
This thesis aimed to: 1) develop methodologies for assessing cardiovascular function and stress responses in guinea pigs, 2) investigate the maturation of cardiovascular control from infancy to childhood; and 3) examine the cardiovascular capacity to respond to both heating and cooling thermal stressors.
Because in humans the insult (preterm birth) and presentation of dysfunction are separated by years, animal models allow us to speed up the trajectory of dysfunction across a shorter lifespan, and pair (patho)physiological changes with the mechanisms underlying this dysfunction. Utilising the established guinea pig model of preterm birth, cardiovascular assessments were performed at corrected postnatal age (CPNA) 0, 7, 35 and 40 days (Chapter 6), with whole-body heating and cooling thermal challenges performed in a randomised order on CPNA 35 or 38 days (equivalent to an 8–10-year-old child; Chapter 7 and 8). To minimise the stress of repeated monitoring from infancy to childhood, an optimised sedative agent and dose rate was determined (alfaxalone, 5 mg.kg-1 IM; Chapter 3). Alfaxalone, a neurosteroid, is safe and effective for repeat administration in juvenile animals and produces mild sedation for procedures lasting ~30 min with minimal cardiovascular effects. For longer procedures, an anaesthetic regime (0.8% isoflurane + 70% N2O) was optimised to ensure minimal cardiovascular and respiratory depression (Chapter 4). Using the stable anaesthetic state, the novel whole-body thermal challenges were developed to comprehensively assess cardiovascular responses to heat and cold stressors (Chapter 5). Cardiovascular assessments utilised both central cardiac (ECG, SBP), and peripheral vascular measures (microvascular perfusion via laser Doppler flowmetry), with cardiovascular control explored utilising heart rate variability (HRV).