Instrumentation of Near-term Fetal Sheep for Multivariate Chronic Non-anesthetized Recordings

Abstract

The chronically instrumented pregnant sheep has been used as a model of human fetal development and responses to pathophysiologic stimuli such as endotoxins, bacteria, umbilical cord occlusions, hypoxia and various pharmacological treatments. The life-saving clinical practices of glucocorticoid treatment in fetuses at risk of premature birth and the therapeutic hypothermia have been developed in this model. This is due to the unique amenability of the non-anesthetized fetal sheep to the surgical placement and maintenance of catheters and electrodes, allowing repetitive blood sampling, substance injection, recording of bioelectrical activity, application of electric stimulation and in vivo organ imaging. Here we describe the surgical instrumentation procedure required to achieve a stable chronically instrumented non-anesthetized fetal sheep model including characterization of the post-operative recovery from blood gas, metabolic and inflammation standpoints.

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].…”

Vagal contributions to fetal heart rate variability: an omics approach

“…We instrumented pregnant time-dated ewes at 126 days of gestation (dGA, ~0.86 gestation) with arterial, venous and amniotic catheters and ECG electrodes as described before. (Burns et al , 2015) For anaesthesia, the ewes were premedicated with acepromazine (Atravet 10 mg/mL) 2 mg intravenously; 30 minutes later, the animals were induced with a combination of diazepam (Diazepam 5 mg/mL) 20 mg, ketamine (Ketalar 100 mg/mL) 4-5 mg/kg and Propofol (Propofol 10 mg/mL) 0.5 to 1 mg/kg. An endotracheal tube was inserted orally and ewes were ventilated in order to maintain a P a CO 2 of 35 to 45 mmHg.…”

“…For the purposes of this study, e ach experiment was completed at 9.00 am with a 1 h baseline measurement followed by the respective intervention as reported elsewhere. (Burns et al , 2015;Durosier et al , 2015) After the +54 hours (Day 3) sampling, the animals were sacrificed. The 72 h post-surgery, i.e., 1 h baseline, time point is reasonable to consider as a post-surgical recovery since the pharmacological effects of the anaesthetic with respect to the cardiovascular system would have worn off by then.…”

Non-invasive acquisition of fetal ECG from the maternal xyphoid process: a feasibility study in pregnant sheep and a call for open data sets

“…We instrumented thirteen pregnant time-dated ewes at 126 days of gestation (dGA, ~0.86 gestation) with arterial, venous and amniotic catheters and ECG electrodes. (Burns et al, 2015) Ovine singleton fetuses of mixed breed were surgically instrumented with sterile technique under general anesthesia (both ewe and fetus). In case of twin pregnancy the larger fetus was chosen based on palpating and estimating the intertemporal diameter.…”

“…Part of the challenge is the requirement to perform a sterile fetal surgical instrumentation with precordial ECG leads. (Burns et al, 2015) The ability to record fetal sheep ECG from the mother's surface, i.e., non-invasively, would reduce the complexity of the model hopefully contributing to its wider utilization and increased availability of testable fetal ECG data sets recorded under well-controlled animal experimental conditions with translational relevance.…”