In adults, vagus nerve stimulation (VNS) reduces inflammation. In neonates,
the effects of VNS are not known. 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
VNS effect on the systemic inflammatory response induced by a high dose of LPS
in neonatal piglets to mimic late-onset neonatal sepsis. Next, we tested if our
HRV inflammatory index tracks inflammation in piglets. 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 cytokines' temporal profile. 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