Efferent activity in the vagus nerve can prevent endotoxin-induced shock by attenuating tumor necrosis factor (TNF) synthesis. Termed the “cholinergic antiinflammatory pathway,” inhibition of TNF synthesis is dependent on nicotinic α-bungarotoxin-sensitive acetylcholine receptors on macrophages. Vagus nerve firing is also stimulated by CNI-1493, a tetravalent guanylhydrazone molecule that inhibits systemic inflammation. Here, we studied the effects of pharmacological and electrical stimulation of the intact vagus nerve in adult male Lewis rats subjected to endotoxin-induced shock to determine whether intact vagus nerve signaling is required for the antiinflammatory action of CNI-1493. CNI-1493 administered via the intracerebroventricular route was 100,000-fold more effective in suppressing endotoxin-induced TNF release and shock as compared with intravenous dosing. Surgical or chemical vagotomy rendered animals sensitive to TNF release and shock, despite treatment with CNI-1493, indicating that an intact cholinergic antiinflammatory pathway is required for antiinflammatory efficacy in vivo. Electrical stimulation of either the right or left intact vagus nerve conferred significant protection against endotoxin-induced shock, and specifically attenuated serum and myocardial TNF, but not pulmonary TNF synthesis, as compared with sham-operated animals. Together, these results indicate that stimulation of the cholinergic antiinflammatory pathway by either pharmacological or electrical methods can attenuate the systemic inflammatory response to endotoxin-induced shock.

VNS significantly attenuates TNF synthesis and shock during reperfusion injury in a standard model of aortic occlusion. Clinical evaluation of VNS for this condition may be warranted.

arterial therapies. This study sought to assess the major complication rates associated with arterial and venous lytic therapies with the hypothesis that the complication rates may be higher with venous as compared to arterial treatments.Methods: This study is a single-center, retrospective review of arterial and venous lytic treatments that were performed between the dates of December 2010 and April 2015. Treatment areas included all arterial and venous beds; however, dialysis access and pulmonary embolism treatments were excluded from the analysis. Treatment protocols for lytic therapy were standardized, with modifications made according to attending discretion. During the pharmacomechanical thrombectomy portion, the appropriate AngioJet rheolytic catheter was used based on the target vessel diameter. A maximum of 10 mg of tPA was used at the index treatment. Lytic therapy was continued postoperatively at a rate of 1 mg/h. This was titrated postoperatively based on serial laboratory examinations of fibrinogen, CBC, PTT, and CPK (arterial cases). The tPA was titrated based on the fibrinogen level: fibrinogen 200-250 (tPA at 0.5 mg/h); fibrinogen <200 (tPA held); fibrinogen <100 or any sign of bleeding (tPA reversal). Access site and systemic complications were evaluated.Results: A total of 93 patients were included in the cohort (A-52 vs V-41). The gender breakdown (% women) did not differ significantly between the two cohorts (A-63% vs V-78%; P ¼ .17). The age did differ significantly between the two cohorts (A-68 years vs V-50 years; P < .01). There were 6 complications (11.5%) in the arterial lytic group, with one associated mortality, and 6 complications (14.6%) in the venous lytic group (P ¼ NS). There were no significant differences in the total number of complications, although the complication types trended towards an increase in systemic complications in the venous patients (P ¼ .2; Table ).Conclusions: This study suggests that the overall complication rates as related to venous lytic therapy are equivalent to those for arterial lytic therapy; however, the nature of the complications may differ, with a trend toward increased systemic complications in venous patients. This study provides for further impetus to evaluate venous lytic treatments as a separate entity from arterial lytic treatments, specifically with regards to indications for treatment, procedural technique and tPA dosing.