(A) Mice with 9- to 17-day-old implants received three doses of VNS over 2 days using previously reported parameters (intensity 1 mA, pulse width [PW] 250 μs, frequency 30 Hz). Lipopolysaccharide (LPS) was administered 5 hr after the last VNS dose, and blood was collected 90 min post-LPS injection. (B) Serum TNF levels from implanted mice that received no LPS (saline) with sham or VNS (first and second bars), sham surgery mice that received LPS (third bar), and implanted mice that received LPS with sham or VNS (fourth and fifth bars). Data shown as mean ± SEM. *p = 0.0177, by Mann–Whitney with Bonferroni correction for multiple comparisons. (C) Mean heart rate (HR) before, during, and after each stimulation event for endotoxemic mice that received VNS. Each line corresponds to a subject with matching shape and color in fifth bar in (B). (D) In a separate experiment, mice with 2- to 6-week-old implants (n = 22) received a single dose of VNS, or sham VNS, for 5 min (intensity at heart rate threshold [HRT], PW 250 μs, frequency 10 Hz). LPS was administered 3 hr after VNS and blood was collected 90 min post-LPS injection. (E) Serum TNF levels from mice that received sham stimulation (left bar), mice that received VNS without a HR response (middle bar), and mice that received VNS that elicited a HR response (right bar). Data shown as mean ± SEM. p NS (VNS with bradycardia vs. sham, and VNS with vs. without bradycardia) by Mann–Whitney with Bonferroni correction for multiple comparisons.