Partial Recovery of Respiratory Function and Diaphragm Reinnervation following Unilateral Vagus Nerve to Phrenic Nerve Anastomosis in Rabbits

Junxiang Wen,Lijun Li,Jun Tan,Guixin Sun,Mingjie Yang,Shawn Hochman

doi:10.1371/journal.pone.0079552

Abstract

Respiratory dysfunction is the leading cause of mortality following upper cervical spinal cord injury (SCI). Reinnervation of the paralyzed diaphragm via an anastomosis between phrenic nerve and a donor nerve is a potential strategy to mitigate ventilatory deficits. In this study, anastomosis of vagus nerve (VN) to phrenic nerve (PN) in rabbits was performed to assess the potential capacity of the VN to compensate for lost PN inputs. At first, we compared spontaneous discharge pattern, nerve thickness and number of motor fibers between these nerves. The PN exhibited a highly rhythmic discharge while the VN exhibited a variable frequency discharge pattern. The rabbit VN had fewer motor axons (105.3±12.1 vs. 268.1±15.4). Nerve conduction and respiratory function were measured 20 weeks after left PN transection with or without left VN-PN anastomosis. Compared to rabbits subjected to unilateral phrenicotomy without VN-PN anastomosis, diaphragm muscle action potential (AP) amplitude was improved by 292%, distal latency by 695%, peak inspiratory flow (PIF) by 22.6%, peak expiratory flow (PRF) by 36.4%, and tidal volume by 21.8% in the anastomosis group. However, PIF recovery was only 28.0%, PEF 28.2%, and tidal volume 31.2% of Control. Our results suggested that VN-PN anastomosis is a promising therapeutic strategy for partial restoration of diaphragm reinnervation, but further modification and improvements are necessary to realize the full potential of this technique.

Highlights

Spinal cord injury (SCI) is a devastating condition resulting in permanent disability or mortality depending on the injury level
We investigated the effectiveness of vagus nerve (VN)-phrenic nerve (PN) anastomosis for respiratory recovery in rabbits with unilateral phrenicotomy by testing respiratory function and compound muscle action potentials (CMAPs) after surgery
The PN is responsible for respiration, which is of constant frequency when metabolism is stable

Summary

Introduction

Spinal cord injury (SCI) is a devastating condition resulting in permanent disability or mortality depending on the injury level. 40% of SCIs occur at the cervical level [1], resulting in respiratory function deficits For those patients with upper cervical SCI, mechanical ventilation (MV) is still the routine choice to sustain life, which is associated with a number of serious side effects, including infection, atelectasis and diaphragm muscle atrophy [2,3,4]. A series of alternative techniques such as intercostal muscle pacing [9,11,12,13], combined intercostal and phrenic nerve pacing [14], and intercostal to phrenic transfer with diaphragmatic pacing [15] have been introduced For all these interventions, the pattern and level of ventilation induced by current pacing systems are fixed and not amenable to physiological control to match metabolic need [5,16]

Methods

Results

Conclusion