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Vagus Nerve Stimulation Attenuates Peripheral Hemorrhage In Rodents And Swine
Author(s) -
Czura Christopher J.,
Schultz Arthur,
Huston Jared M,
Kaipel Martin,
Khadem Anna,
Ochani Mahendar,
Ochani Kanta,
Redl Heinz,
Tracey Kevin J.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1422
Subject(s) - vagus nerve stimulation , stimulation , vagus nerve , medicine , endocrinology , cholinergic , peripheral nervous system , anesthesia , chemistry , central nervous system
The central nervous system regulates peripheral immune responses via the vagus nerve, the primary neural component of the cholinergic anti‐inflammatory pathway. The vagus neurotransmitter, acetylcholine, suppresses endotoxin‐stimulated cytokine release from macrophages and adhesion molecule expression on endothelial cells (Nature 420:853; J Exp. Med. 201:1113). Electrical vagus nerve stimulation suppresses pro‐inflammatory cytokine release in response to endotoxin and hypovolemic shock, and protects against lethal hypotension (J Intern. Med. 257:156). Surprisingly, electrical vagus nerve stimulation also significantly decreased bleeding time (sham = 213.5 ± 9.5 sec, vs. electrical stimulation = 92.4 ± 2.2 sec; p < 0.001) in male BALB/c mice subjected to tail amputation, without affecting systemic coagulation parameters. In a pig partial ear resection model, vagus nerve stimulation significantly decreased bleeding time by 44% (sham = 1032 ± 228 sec vs. electrical stimulation = 584 ± 121 sec; p=0.04) and total blood loss by 46% (sham = 48.4 ± 6.8 mL vs. electrical stimulation = 26.3 ± 6.7 mL; p=0.03). Vagus nerve stimulation reduced bleeding time independently of changes in heart rate or blood pressure, but correlated with increased generation of thrombin/antithrombin complexes in shed blood. These data indicate that electrical stimulation of the vagus nerve attenuates peripheral hemorrhage in murine and porcine models of soft tissue injury, and that this protective effect is associated with local increases in coagulation factor activity. This work was supported by DARPA.