Cervical Vagal Nerve Stimulation Restores Ventilatory Pattern Variability in an E. Coli Sepsis Rodent Model.

Abstract

Sepsis is a life‐threatening disease characterized by dysregulated systemic inflammation and organ failure. We have associated an increase in predictability of the ventilatory pattern variability (VPV) with progressive development of systemic inflammation leading to sepsis. Vagal nerve stimulation (VNS) is a proposed electro‐therapeuty that reduces circulating pro‐inflammatory cytokines, like interleukin‐1 beta (IL‐1β), that are associated with systemic inflammation. We hypothesize that the anti‐inflammatory effects of VNS will be reflected in reduced predictability of VPV. Urethane‐anaesthetized adult Sprague Dawley male rats (350–400g n=17) were instrumented for blood pressure (BP), heart rate (HR), and airflow (pneumotach). The left cervical vagus was dissected, isolated and prepared for electrical stimulation via nerve cuff. Each rat was subjected to a staircase protocol of monophasic electrical stimulus pulses (0.6 mA, 0.1 ms pulse width, 10 Hz) to identify the maximal current that was subthreshold for cardiac and respiratory responses. Four experimental cohorts were then established: 1) (+stim/+E. coli) (n=4), 2) (−stim/+E. coli) (n=5), 3) (+stim/−E. coli) (n=2), 4) (−stim/−E. coli) (n=6). In +stim groups, a stimulus train was initiated 10 min before and continued for 20 min after an E. coli solution (60 μg/kg rat; 50,000 cells suspended in normal saline) was injected intravenously (IV). The effects of stimulation on the systemic inflammatory response were determined by comparing serum cytokine levels prior to stimulation to those 90 min after inoculation and the effects on VPV was quantified from non‐linear complexity index (NLCI) prior to the blood draws. Cervical VNS reduced expression of IL‐1β from 102.33 ± 49 pg/ml to 69.50 ± 28 pg/ml and reduced NLCI (0.57 ± 0.04 bits to 0.48 ± 0.03 bits; p < 0.001). VPV became more predictable with the infusion of E. Coli and VNS in the presence of E. coli infusion reduced IL‐1β expression and decreased NLCI. These data suggest that VNS impacts both peripheral and central inflammation during E. Coli infusion.Support or Funding InformationSupported by U01 EB021960, and VA I01BX004197