Modulation of brain dead induced inflammation by vagus nerve stimulation.
Because the vagus nerve is implicated in control of inflammation, we investigated if brain death (BD) causes impairment of the parasympathetic nervous system, thereby contributing to inflammation. BD was induced in rats. Anaesthetised ventilated rats (NBD) served as control. Heart rate variability (HRV) was assessed by ECG. The vagus nerve was electrically stimulated (BD + STIM) during BD. Intestine, kidney, heart and liver were recovered after 6 hours. Affymetrix chip-analysis was performed on intestinal RNA. Quantitative PCR was performed on all organs. Serum was collected to assess TNFalpha concentrations. Renal transplantations were performed to address the influence of vagus nerve stimulation on graft outcome. HRV was significantly lower in BD animals. Vagus nerve stimulation inhibited the increase in serum TNFalpha concentrations and resulted in down-regulation of a multiplicity of pro-inflammatory genes in intestinal tissue. In renal tissue vagal stimulation significantly decreased the expression of E-selectin, IL1beta and ITGA6. Renal function was significantly better in recipients that received a graft from a BD + STIM donor. Our study demonstrates impairment of the parasympathetic nervous system during BD and inhibition of serum TNFalpha through vagal stimulation. Vagus nerve stimulation variably affected gene expression in donor organs and improved renal function in recipients.
Hoeger
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S
Department of Medicine V (Nephrology/Endocrinology/Rheumatology), University Medical Center Mannheim, University of Heidelberg, and Clinic for Anaesthesiology and Intensive Care Medicine, University Hospital of Mannheim, Mannheim, Germany. Simone.Hoeger@medma.uni-heidelberg.de
Bergstraesser
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C
Selhorst
J
J
Fontana
J
J
Birck
R
R
Waldherr
R
R
Beck
G
G
Sticht
C
C
Seelen
M A
MA
van Son
W J
WJ
Leuvenink
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Ploeg
R
R
Schnuelle
P
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Yard
B A
BA
D000758:Anesthesia; D000818:Animals; D001926:Brain Death / Q000175:diagnosis*; D015536:Down-Regulation; D004562:Electrocardiography / Q000379:methods; D006339:Heart Rate; D007249:Inflammation / Q000473:pathology*; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014630:Vagus Nerve / Q000473:pathology; D055536:Vagus Nerve Stimulation / Q000379:methods*
D014409:Tumor Necrosis Factor-alpha