title: The effect of late gestation foetal hypoglycaemia on cardiovascular and endocrine function in sheep.
abstract: An appropriate foetal cardiovascular (CV) response to reduced substrate supply (e.g. oxygen or other nutrients) is vital for growth and development, and may impact on CV control. The prevailing nutritional environment and associated CV changes may influence subsequent CV responses to challenges during late gestation, for example, umbilical cord occlusion (UCO). We investigated the effect of low-circulating glucose on foetal CV control mechanisms and response to UCO. Under general anaesthesia, late gestation foetal sheep (n = 7, 119 days gestational age (dGA), term ∼147 days) were implanted with vascular catheters, a bladder catheter, electrocardiogram electrodes and an umbilical cord occluder. Mean arterial pressure (MAP), heart rate (HR) and kidney function were monitored during maternal saline (MSAL, 125dGA) and insulin (MINS, 126dGA) infusion, and foetal CV responses were assessed during incremental doses of angiotensin II, a 90-s total UCO, and administration of phenylephrine to assess baroreflex function. During MINS infusion, the decrease in maternal and foetal blood glucose was associated with a small but significant decrease in foetal HR and reduced foetal baroreflex sensitivity (P < 0.05). The increase in foetal MAP during a 90-s UCO was greater during hypoglycaemia (P < 0.05). The MAP response to angiotensin II was not affected by hypoglycaemia. Decreased foetal HR and baroreflex sensitivity and increased CV responsiveness to UCO during hypoglycaemia indicates altered CV homoestatic mechanisms. The combination of altered nutrition and a CV challenge, such as UCO, during late gestation may have a cumulative effect on foetal CV function.
authors.affiliation: 1The Institute of Developmental Sciences, Southampton General Hospital, University of Southampton, Hampshire, UK.
authors.forename: J K
authors.initials: JK
authors.lastname: Cleal
authors.affiliation: 2Department of Medicine, Oregon Health & Science University, Portland, OR, USA.
authors.forename: S
authors.initials: S
authors.lastname: Bagby
authors.affiliation: 1The Institute of Developmental Sciences, Southampton General Hospital, University of Southampton, Hampshire, UK.
authors.forename: M A
authors.initials: MA
authors.lastname: Hanson
authors.affiliation: 3Institute of Reproductive and Developmental Biology, Faculty of Medicine, Imperial College, Queen Charlotte's and Chelsea Hospital, London, UK.
authors.forename: H M
authors.initials: HM
authors.lastname: Gardiner
authors.affiliation: 1The Institute of Developmental Sciences, Southampton General Hospital, University of Southampton, Hampshire, UK.
authors.forename: L R
authors.initials: LR
authors.lastname: Green