Histopathology of the stimulated Vagus nerve: primum non nocere.

A primary concern in the utilization of implantable neural interfaces for the treatment of medical diseases is to follow the Hippocratic dictum: First, do no harm. If we are to avoid harm to the Vagus nerve in our use of stimulatory electrodes in the treatment of heart failure, we must understand the structural and functional elements that comprise peripheral nerves, their susceptibility to various types of injury that might be expected to occur secondary to functional electrical stimulation and how to separate the various components of the response of peripheral nervous system elements to stresses that may occur in the complex interactions that take place between electrode and nerve. To this end, we review the functional histology of peripheral nerve, followed by a consideration of salient types of nerve injuries, which have been elucidated through the combination of careful observations of human disease and well-constructed experimental models. We then examine the extant literature on stimulation-induced nerve injury in light of recent developments in the understanding of electropermeabilization of biological membranes. Finally, we briefly discuss our experience using the CardioFit™ electrode on the canine Vagus nerve.