Parasympathetic nervous system response to acidosis: Evaluation in an experimental fetal sheep model

Abstract

| INTRODUC TI ONThe occurrence of decreased maternal-fetal gas exchange during labor may lead to fetal acidosis, which can be responsible for severe neonatal complications including a risk of cerebral palsy. It is recognized that about 10% of cases of cerebral palsy are caused by peripartum asphyxia. 1 Recent guidelines highlighted the importance of knowledge of fetal physiology to improve the interpretation of fetal heart rate (FHR) changes during labor. 2 However, changes in FHR are an imperfect reflection of fetal adaptation to hypoxia.Abbreviations: ANS, autonomic nervous system; FHR, fetal heart rate; FSI, fetal stress index; HF, high-frequency; HRV, heart rate variability; LF, low-frequency; MAP, mean arterial pressure; UCO, umbilical cord occlusion. 1 EA 4489 -Perinatal Environment and Health, Abstract Introduction: Heart rate variability and fetal heart rate decelerations are impacted by parasympathetic function and reflect acid-base status. Our team developed a new heart rate variability index, the fetal stress index (FSI), which has lower interindividual variability and higher sensitivity for detecting fluctuations in parasympathetic nervous system activity. The aim of this study was to explore the ability of the FSI to predict fetal acidosis in a fetal sheep model. Material and methods: Repeated 1-minute total umbilical cord occlusions (UCOs)were performed every 2.5 minutes over 3 hours to generate fetal acidosis mimicking that which occurs during labor and contractions. Fetal hemodynamic parameters, blood gas, the FSI and the magnitude (from the beginning to the nadir) of the fetal heart rate deceleration were recorded at regular intervals. The data were analyzed over three time intervals because of variation in the duration of the experiments: period A (first 12 UCOs), period B (middle 12 UCOs) and period C (last 12 UCOs). Results:Nine experiments were performed. Acidosis was progressive with a significant difference between the pH, lactate levels and base deficit values for the three periods of occlusion (P < 0.05). Both FSI and the magnitude of fetal heart rate decelerations gradually increased during the UCOs and both differed significantly between periods A and C (P = 0.0008 for FSI and P = 0.003 for deceleration). Conclusion:This experimental protocol allowed the development of progressive acidosis in a good model of the physiology of labor. Parasympathetic nervous system activity increased during acidosis and could be measured using our index, the FSI, and the magnitude of fetal heart rate decelerations. K E Y W O R D Sacidosis, fetal heart rate, fetal sheep, fetal stress index, parasympathetic nervous system

Parasympathetic activity is the key regulator of heart rate variability between decelerations during brief repeated umbilical cord occlusions in fetal sheep

“…In the present study, parasympathetic blockade by either bilateral cervical vagotomy or atropine sulfate infusion essentially abolished FHRV between brief repeated UCOs, which were designed to mimic the pattern of fetal hypoxemia during labor. These findings demonstrate that the increase in measures of FHRV observed early during more prolonged paradigms of repeated UCOs (12,17,26,31,49) is entirely mediated by increased parasympathetic activity. The combination of the present findings with our previous studies of the roles of the R548 PARASYMPATHETIC REGULATION OF FHRV neural and adrenal sympathetic systems (25,26) strongly confirms that SNS control of FHRV is acutely suppressed after acute fetal hypoxemia, leaving the parasympathetic nervous system as the key regulator of FHRV during labor-like hypoxia.…”

“…Furthermore, increased intrapartum STV has been associated with increased fetal scalp lactate levels (32), and increased FHRV on visual inspection was associated with an increase in risk of acidemia at birth (39). Systematic studies in fetal sheep have demonstrated that fetal compromise can be associated with both increased and suppressed FHRV (12,17,26,31,49). Our understanding of both the clinical utility and physiological underpinnings of intrapartum FHRV remains surprisingly incomplete despite FHRV being a critical, routinely used index of fetal wellbeing.…”

Experimental Infection of Pregnant Female Sheep with Zika Virus During Early Gestation

“…This model is especially important as one of the few that allows for continuous fetal monitoring by in utero instrumentation [17,18,19]. Maternal and fetal telemetric or electrocardiographic leads and catheters (arterial, venous, umbilical, and amniotic) can be surgically placed to continuously monitor metabolic activity, nutrient and gas exchange, and cytokine presence, and to frequently obtain physiologic measurements and biological samples at the maternal–fetal interface [20,21,22,23]. The ability to closely monitor the maternal–fetal interface has led to the extensive use of sheep as model for human pregnancy and fetal development over the last half a century, and has contributed to an understanding of fetal stress and intrauterine growth restriction—both of which are components of maternal ZIKV infection and CZS [17,24,25,26,27,28].…”

Associations between fetal heart rate variability and umbilical cord occlusions‐induced neural injury: An experimental study in a fetal sheep model

“…Our team developed the fetal stress index (FSI) based on an original HRV analysis method 11 that combined time and spectral analysis 10 . In previous experimental studies using a model of repeated cord occlusion in fetal sheep, we demonstrated that this index was related to variations in parasympathetic activity 11 and correlated with acid‐base status 13 . Such a biomarker may constitute a new pathway for evaluating fetal well‐being during labor 14 …”