  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.
