  An electrocardiogram (ECG)-derived heart rate variability (HRV) index
reliably tracks the inflammatory response induced by low-dose
lipopolysaccharide (LPS) in near-term sheep fetuses. We evaluated the effect of
vagus nerve stimulation (VNS) on vagus nerve electroneurogram (VENG) and the
systemic inflammatory response induced by a high dose of LPS in neonatal
piglets to mimic late-onset neonatal sepsis. We tested if our HRV inflammatory
index tracks inflammation in piglets and its relationship to VENG. Following
anesthesia, electrodes were attached to the left vagal nerve; ECG and blood
pressure (BP) were recorded throughout the experiment. Following baseline, the
piglets were administered LPS as 2mg/kg IV bolus. In the VNS treated piglet,
the vagus nerve was stimulated for 10 minutes prior to and 10 min after the
injection of LPS. In both groups, every 15 min post LPS, the arterial blood
sample was drawn for blood gas, metabolites, and inflammatory cytokines. At the
end of the experiment, the piglets were euthanized. BP and HRV measures were
calculated. The piglets developed a potent inflammatory response to the LPS
injection with TNF-alpha, IL-1beta, IL-6 and IL-8 peaking between 45 and 90 min
post-injection. VNS diminished the LPS-induced systemic inflammatory response
varying across the measured cytokines from two to ten-fold. The HRV index
tracked accurately the temporal profile of cytokines and VENG changes. This
novel model allows manipulating and tracking neonatal sepsis: The HRV
inflammatory index 1) applies across species pre- and postnatally and 2)
performs well at different degrees of sepsis (i.e., nanogram and milligram
doses of LPS); 3) the present VNS paradigm effectively suppresses LPS-induced
inflammation, even at high doses of LPS. The potential of early postnatal VNS
to counteract sepsis and of HRV monitoring to early detect and track it deserve
further study.
