Peripheral chemoreflex activation and cardiac function during hypoxemia in near-term fetal sheep without placental compromise

Abstract

A drop in arterial oxygen content activates fetal chemoreflex including an increase in sympathetic activity leading to peripheral vasoconstriction and redistribution of blood flow to protect the brain, myocardium, and adrenal glands. By using a chronically instrumented fetal sheep model with intact placental circulation at near-term gestation, we investigated the relationship between peripheral chemoreflex activation induced by hypoxemia and central hemodynamics. 17 Åland landrace sheep fetuses at 115-128/145 gestational days were instrumented. Carotid artery was catheterised in 10 fetuses and descending aorta in 7 fetuses. After a 4-day recovery, baseline measurements of fetal arterial blood pressures, blood gas values, and fetal cardiovascular hemodynamics by pulsed Doppler ultrasonography were obtained under isoflurane-anesthesia. Comparable data to baseline was collected 10 (acute hypoxemia) and 60 minutes (prolonged hypoxemia) after maternal hypo-oxygenation to saturation level of 70-80% was achieved. During prolonged hypoxemia, pH and base excess (BE) were lower, and lactate levels higher in the descending aorta than in the carotid artery. During hypoxemia mean arterial blood pressure (MAP) in the descending aorta increased, while in the carotid artery MAP decreased. In addition, right pulmonary artery pulsatility index values increased, and the diastolic component in the aortic isthmus blood flow velocity waveform became more retrograde. Both fetal ventricular cardiac outputs were maintained even during prolonged hypoxemia when significant fetal metabolic acidemia developed. Fetal chemoreflex activation induced by hypoxemia decreased the perfusion pressure in the cerebral circulation. Fetal weight-indexed LVCO or AoI Net Flow-ratio did not correlate with a drop in carotid artery blood pressure.

Increased variability of fetal heart rate during labour: a review of preclinical and clinical studies

“…29,77 Many studies in chronically instrumented fetal animals have used simulated intrapartum stress to improve clinical understanding of compensation mechanisms in the human fetus during birth, as well as the accompanying changes in FHR and FHRV. 47,[78][79][80][81][82][83] Animal studies can be broadly separated into those that study sustained periods of hypoxaemia and those that study intermittent periods of repeated hypoxaemia. The latter is more characteristic of the repetitive nature of hypoxaemia during intrapartum uterine contractions.…”

“…27,36,79,84,94,95 In contrast, more recent studies in fetal sheep have employed multiple forms of autonomic blockade during repeated UCOs to illustrate that FHRV during labour (once repetitive decelerations are apparent) is solely mediated by the parasympathetic nervous system, as recently reviewed. 96 For example, neither complete β-adrenergic blockade with propranolol 83,97,98 nor chemical sympathectomy with 6-hydroxydopamine neurotoxin 37,99 reduced FHRV during repeated UCOs. In contrast, FHRV was abolished with parasympathetic blockade with either atropine sulphate or bilateral vagotomy.…”

“…intermittent gas exchange disruption and consequent fetal hypoxaemia caused by intense uterine contractions, contributes to the intrapartum increased FHRV pattern 29,77 . Many studies in chronically instrumented fetal animals have used simulated intrapartum stress to improve clinical understanding of compensation mechanisms in the human fetus during birth, as well as the accompanying changes in FHR and FHRV 47,78–83 . Animal studies can be broadly separated into those that study sustained periods of hypoxaemia and those that study intermittent periods of repeated hypoxaemia.…”

In utero deposition of trace elements and metals in tissues

“…The study protocol was approved by the National Animal Experiment Board of Finland (ESAVI/1007/04.10.07/ 2014). The animals were primarily used for fetal asphyxia [14] and oxycodone pharmacokinetics [15] studies, and the present study only utilized tissues of anesthetized and euthanized animals. The first group of sheep were operated in the fall of 2017 (n = 7).…”