Newman, James Paul; (2000) Near infrared spectroscopy in the investigation of fetal responses to stress. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Intrauterine stressors are implicated in the development of a significant proportion of cases of perinatal brain injury, which may result in death of the infant or in deficits in motor and/or intellectual development. Whilst stressors such as reduction in oxygen delivery to the fetus or fetal infection are believed to be have important roles in the development of perinatal brain injury, our understanding of the sequences of events leading from stressor to injury is in incomplete. My aim in performing the experiments presented in this thesis was therefore to use biophysical monitoring and near infrared spectroscopy to investigate fetal cerebral and peripheral cardiovascular and metabolic responses (A) to simulated fetal infection by intravenous administration of bacterial lipopolysaccharide to the fetus, and (B) to severe hypoxia-asphyxia induced in the mid- and late-gestation fetal sheep by either reduction in uterine artery flow or complete umbilical cord occlusion. In these experiments chronically instrumented fetal sheep at either 0.6 or 0.8 of gestation were implanted with vascular catheters and a range of probes to permit chronic fetal monitoring without the confounding effects of anaesthesia. Fetal heart rate and mean arterial pressure were monitored by use of vascular catheters placed in brachial and/or femoral artery. These catheters allowed blood samples to be taken which could be analysed to provide data on blood pH, blood gas tensions, oxygen content and haemoglobin saturation. Coupled with measurements of flow from jugular and/or femoral vein, calculation of oxygen delivery to and consumption by both the brain and femoral skeletal muscle bed was possible. Additionally, use of a purpose-built continuous wavelength CCD near infrared spectrometer (NIR) provided continuous measurements of change in the absolute concentration of oxyhaemoglobin (HbO2), deoxyhaemoglobin (Hb) and oxidised cytochrome oxidase (CcO) in fetal brain and peripheral muscle during hypoxia and asphyxia. My important findings are; 1. Fetal haemodynamic responses to acute severe reduction in uterine artery flow at 0.6 and 0.8 of gestation are qualitatively similar but differ in magnitude, indicating that the systems required for reflex adaptation to hypoxia - asphyxia are present and functional at 0.6 of gestation. 2. The ability of mid-gestation fetuses to maintain adaptations to severe hypoxia are attenuated compared to late- gestation animals and, despite receiving severe asphyxic challenges from uterine artery occlusion, there was no evidence of repeatable, severe brain injury at either 0.6 or 0.8 of gestation. 3. Cerebral CcO, at both 0.6 and 0.8 of gestation, oxidises during hypoxia. Simultaneously, femoral skeletal muscle CcO became reduced. Since O2 consumption fell in both brain and skeletal muscle, the CcO data indicates that subtle metabolic alterations can be made regionally, with perhaps more important tissues retaining more metabolic activity during hypoxic stress. 4. In late-gestation, severe umbilical cord occlusion results in temporary haemodynamic adaptation and CcO oxidation. When this insult is maintained, fetal cardiovascular collapse and CcO reduction begin. Histological evidence of hippocampal injury was present in all bar one of the fetuses exposed to this insult. 5. Exogenous infusion of adenosine, at a rate which does not dramatically alter haemodynamics, reduced fetal cerebral O2 consumption through an unknown mechanism and results in CcO oxidation similar to that seen during hypoxia. 6. A high nanogram dose of bacterial lipopolysaccharide administered iv to the fetal results in mild haemodynamic perturbation and severe brain injury.

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