Recording and manipulation of vagus nerve electrical activity in chronically instrumented unanesthetized near term fetal sheep

TL;DR

This paper introduces a new surgical method for implanting vagus nerve stimulation and recording devices in chronically instrumented, unanesthetized fetal sheep, enabling in vivo study of vagus nerve activity during development.

Contribution

It presents a novel surgical procedure and device design for chronic vagus nerve stimulation and recording in fetal sheep, a large mammalian model of human pregnancy.

Findings

Successful implantation of VNS probes in fetal sheep.

Recorded vagus nerve activity (VENG) in vivo.

Observed changes in blood and inflammatory markers post-surgery.

Abstract

Background: The chronically instrumented pregnant sheep has been used as a model of human fetal development and responses to pathophysiologic stimuli. This is due to the unique amenability of the unanesthetized 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. Recently, there has been growing interest in pleiotropic effects of vagus nerve stimulation (VNS) on various organ systems such as innate immunity, metabolism, and appetite control. There is no approach to study this in utero and corresponding physiological understanding is scarce. New Method: Based on our previous presentation of a stable chronically instrumented unanesthetized fetal sheep model, here we describe the surgical instrumentation procedure allowing successful implantation of a cervical uni- or bilateral VNS probe with or without vagotomy. Results: In a cohort of 53 animals, we present the changes in blood gas, metabolic, and inflammatory markers during the postoperative period. We detail the design of a VNS probe which also allows recording from the nerve. We also present an example of vagus electroneurogram (VENG) recorded from the VNS probe and an analytical approach to the data. Comparison with Existing Methods: This method represents the first implementation of VENG/VNS in a large pregnant mammalian organism. Conclusions: This study describes a new surgical procedure allowing to record and manipulate chronically the vagus nerve activity in an animal model of human pregnancy.