The effect of repeated acute hypoxaemia on fetal cardiovascular development in the sheep

Abstract

1. Hypoxaemia during intrauterine life may be important in the development of cardiovascular diseases in later life. Thus it was the aim of this study to investigate the effect of repeated acute hypoxia on the cardiovascular development and growth of the fetus. 2. Fourteen fetal sheep (105-109 days gestational age) were instrumented with amniotic and vascular catheters, an electrocardiogram (ECG) electrode and a flow probe around the femoral artery. Seven animals were given repeated acute isocapnic hypoxaemia (Pa,Oµ reduced to ca. 13 mmHg) for 1 h every day for 14 days and they were compared to seven animals which remained normoxic throughout with respect to fetal mean arterial blood pressure (MAP), fetal heart rate (FHR), and fetal baro-and chemoreflexes. 3. No differences were found between the two groups of fetuses in FHR, MAP, baro-or chemoreflexes, femoral blood flow, femoral vascular resistance or fetal growth. 4. Repeated acute hypoxaemia of a moderate degree over a period of 2 weeks in late gestation does not affect cardiovascular development or growth in the fetal sheep.

Adaptation of cardiovascular responses to repetitive umbilical cord occlusion in the late gestation ovine fetus

“…These findings concur with, and extend those of, our previous study in which the same cardiovascular variables were recorded over a period of time equivalent to the first 4 days of the current study (Green et al 1999). Other studies in the ovine fetus using more moderate continuous ( P O2 to ≈19 mmHg; Kitanaka et al 1989) or daily 1 h ( P O2 to ≈13 mmHg; Steyn & Hanson, 1998) hypoxaemic challenges, by alteration of maternal inspired gases, for 2‐3 weeks from ≈110 days of gestation have also shown that MAP and FHR developmental trajectories are unaltered. In contrast, Shinozuka et al (2000) have recently observed that an increased frequency of myometrial contractures in ewes, induced by pulsed oxytocin administration, over the last 50 days of gestation results in higher fetal arterial blood pressure and lower FHR, possibly mediated by fetal hypoxia or stimulation of endocrine axes such as the hypothalamic‐pituitary‐adrenal (HPA) axis.…”

Programming of Endocrine Mechanisms of Cardiovascular Control and Growth

“…An increase in plasma catecholamine levels resulting from increased activity of the sympathetic nervous system, rather than the adrenal medulla, is thought to account for the developmental increase in fetal arterial pressure in late gestation29 acting via ct and 3 receptors. The catecholamine response to hypoxia is functional by [95][96][97][98][99][100][101][102][103][104][105][106][107][108][109][110][111][112] days' gestation in the sheep fetus30 and, in common with elevated circulating levels of epinephrine and norepinephrine in spontaneously growthrestricted ovine fetuses,31 this is likely to originate predominantly from the adrenal gland with contributions from paraganglia and sympathetic overflow.28 During hypoxia, after the initial rapid vagally mediated bradycardia, fetal heart rate returns to or above baseline levels. This recovery of heart rate is attributed to increased sympathetic efferent activity and to direct action of elevated circulating catecholamine levels on the heart, and it is abolished by P3-adrenergic blockade.…”

Prenatal nicotine exposure affects cardiovascular function and growth of the developing fetus

“…The blood nicotine concentrations of mothers injected with nicotine 0.2 mg/kg peaked at 31.0 ± 0.57 ng/mL and 15‐min postinjection. When humans smoke, their peak nicotine blood concentration is generally considered to be 20–50 ng/mL; thus, we believe that the nicotine dose in the current study was appropriate 18,19 . Nicotine acts by stimulating the sympathetic ganglia, releasing norepinephrine and causing the adrenal medulla to release epinephrine and norepinephrine.…”

“…When humans smoke, their peak nicotine blood concentration is generally considered to be 20-50 ng/mL; thus, we believe that the nicotine dose in the current study was appropriate. 18,19 Nicotine acts by stimulating the sympathetic ganglia, releasing norepinephrine and causing the adrenal medulla to release epinephrine and norepinephrine. It also stimulates chemoreceptors in the aortic and carotid bodies, reflexively increasing HR, causing vasoconstriction and raising BP.…”

“…In the fetal programming theory, if a fetus is exposed to stressors in utero , such as drugs or a poor nutritional state, the fetus tries to conform to a ‘thrifty phenotype’ by making circulatory adjustments, energy metabolism adjustments and endocrine adjustments. When a ‘thrifty phenotype’ persists postnatally, it overcompensates for life in the extrauterine environment, leading to the development of lifestyle‐related diseases such as obesity, impaired glucose tolerance, heart disease and hypertension 18 . In considering the effects of nicotine on the fetal programing, it is important to examine the effects of nicotine on fetal hemodynamics during organogenesis.…”