Published online before print February 10, 2003, doi: 10.1161/01.CIR.0000050627.90734.ED
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(Circulation. 2003;107:1189.)
© 2003 American Heart Association, Inc.
Basic Science Reports |
Efferent Vagal Fibre Stimulation Blunts Nuclear Factor-
B Activation and Protects Against Hypovolemic Hemorrhagic Shock
From the Department of Biomedical Sciences, Section of Pharmacology (S.G., M.M.C., D.G., A.B.) and Department of Biomedical Sciences, Section of Physiology (A.B.), University of Modena and Reggio Emilia, Modena, and Department of Clinical and Experimental Medicine and Pharmacology, Section of Pharmacology (D.A., H.M., L.M., F.S.), Department of Internal Medicine (G.S.), Department of Biochemical, Physiological and Nutritional Sciences (R.M., E.B.A.), and Department of Neurosciences, Psychiatry and Anesthesiology (F.S.V.), University of Messina, Italy.
Correspondence to Francesco Squadrito, MD, Department of Clinical and Experimental Medicine and Pharmacology, Section of Pharmacology, University of Messina, AOU "G. Martino," Via Consolare Valeria, Policlinico, Gazzi, Torre Biologica 5° Piano, 98125 Messina, Italy. E-mail Francesco.Squadrito{at}unime.it
Background— We investigated whether electrical stimulation (STIM) of efferent vagus nerves may suppress nuclear factor (NF)-
B activation and the inflammatory cascade in hemorrhagic (Hem) shock.
Methods and Results— Rats were subjected to bilateral cervical vagotomy (VGX) or sham surgical procedures. Hem shock was induced by intermittent withdrawing of blood until mean arterial pressure stabilized within the range of 35 to 40 mm Hg. Application of constant voltage pulses to the caudal vagus ends (STIM; 5 V, 2 ms, 1 Hz for 12 minutes, 5 minutes after mean arterial pressure stabilization) increased survival time (VGX+Hem+Sham STIM=38±3 minutes; VGX+Hem+STIM >180 minutes), reverted the marked hypotension (VGX+Hem+Sham STIM=33±3 mm Hg; VGX+Hem+STIM=66±5 mm Hg), inhibited IB
liver loss, and blunted the augmented NF-B activity, decreased hepatic tumor necrosis factor (TNF)- mRNA (VGX+Hem+Sham STIM=1.42±0.5 amount of TNF- m-RNA; VGX+Hem+STIM=0.51±0.2 amount of TNF- mRNA), and reduced plasma TNF- (VGX+Hem+Sham STIM=190±24 pg/mL; VGX+Hem+STIM=87±15 pg/mL). Chlorisondamine, a nicotinic receptor antagonist, abated the effects of vagal stimulation.
Conclusions— Our results show a parasympathetic inhibition of NF-B by which the brain opposes NF-B activation in the liver and modulates the inflammatory response during acute hypovolemic hemorrhagic shock.
Key Words: vagus nerve • hemorrhage • shock • acetylcholine • inflammation
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