Vagus nerve stimulation inhibits activation of coagulation and fibrinolysis during endotoxemia in rats.
BACKGROUND
Sepsis and endotoxemia are associated with concurrent activation of inflammation and the hemostatic mechanism, which both contribute to organ dysfunction and death. Electrical vagus nerve stimulation (VNS) has been found to inhibit tumor necrosis factor (TNF)-alpha release during endotoxemia in rodents.


OBJECTIVE
To determine the effect of VNS on activation of coagulation and fibrinolysis.


METHODS
Rats received a sublethal i.v. dose of lipopolysaccharide (LPS) after electrical VNS or sham stimulation. Activation of coagulation and fibrinolysis, as well as cytokine release, was measured before LPS injection and 2, 4 and 6 h thereafter.


RESULTS
LPS induced activation of the coagulation system (increases in the plasma concentrations of thrombin-antithrombin complexes and D-dimer, and a decrease in antithrombin) and biphasic changes in the fibrinolytic system [early rises of plasminogen activator activity and tissue-type plasminogen activator, followed by a delayed increase in plasminogen activator inhibitor type 1 (PAI-1)]. VNS strongly inhibited all LPS-induced procoagulant responses and more modestly attenuated the fibrinolytic response. In addition, VNS attenuated the LPS-induced increases in plasma and splenic concentrations of the proinflammatory cytokines TNF-alpha and interleukin-6 (IL-6), while not influencing the release of the anti-inflammatory cytokine IL-10.


CONCLUSIONS
These data illustrate a thus far unrecognized effect of VNS and suggest that the cholinergic anti-inflammatory pathway not only impacts on inflammation but also on the coagulant-anticoagulant balance.
van Westerloo
D J
DJ
Center for Infection and Immunity Amsterdam, CINIMA, Amsterdam, the Netherlands.
Giebelen
I A J
IA
Meijers
J C M
JC
Daalhuisen
J
J
de Vos
A F
AF
Levi
M
M
van der Poll
T
T
D000818:Animals; D001777:Blood Coagulation; D004558:Electric Stimulation; D004599:Electric Stimulation Therapy; D019446:Endotoxemia / Q000473:pathology / Q000628:therapy*; D005342:Fibrinolysis; D007249:Inflammation / Q000517:prevention & control; D016753:Interleukin-10 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D007700:Kinetics; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014630:Vagus Nerve
D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10