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.

Hemoglobin is an endotoxin (lipopolysaccharide; LPS)-binding protein that synergistically increases the release of proinflammatory cytokines from the innate immune system in response to LPS. It has been suggested that this activity of hemoglobin facilitates the recognition of Gram-negative bacteria in a wound, thereby maximizing immune efficiency. This synergy may be important to the pathogenesis of a broad spectrum of clinical conditions because elevated hemoglobin levels frequently are observed in patients after the transfusion of red cells, trauma, cardiopulmonary bypass surgery, hemolysis, in addition to other disorders. To determine the molecular basis of the specific hemoglobin-LPS synergy, in this article we tested the effects of globin itself on macrophage responses to LPS. Paradoxically, these studies revealed that globin suppressed tumor necrosis factor (TNF) synthesis in LPS-stimulated murine and human macrophage cultures. LPS comigrated with globin on non-denaturing electrophoretic gels, giving direct evidence for binding. Globin specifically inhibited LPS activity in the standard Limulus assay but did not inhibit interleukin-1beta-mediated TNF synthesis. Iron supplementation of macrophage cultures significantly increased interleukin-1beta-induced TNF release. Intraperitoneal administration of globin protected mice against both LPS-induced lethality and experimentally induced bacterial infection. Thus, the heme-iron moiety of hemoglobin, and not the binding of LPS to globin, enhanced macrophage responses to LPS.

Pseudoaneurysm of the subclavian-vertebral artery junction (SVJ) is a rare complication of internal jugular vein catheter placement. Because of its retroclavicular location, arterial injury at the SVJ poses a significant therapeutic challenge. A case report and review of the literature are presented.

BackgroundThoracic aortic dissection (TAD) and aneurysm (TAA) are rare but catastrophic. Prompt recognition of TAD/TAA and differentiation from acute coronary syndrome (ACS) is difficult yet crucial. Earlier identification of TAA/TAD based upon routine emergency department screening is necessary.MethodsA retrospective analysis of patients that presented with acute thoracic complaints to the ED from January 2007 through June 2012 was performed. Cases of TAA/TAD were compared to an equal number of controls which consisted of patients with the diagnosis of ACS. Demographics, physical findings, EKG, and the results of laboratory and radiological imaging were compared. P-value of > 0.05 was considered statistically significant.ResultsIn total, 136 patients were identified with TAA/TAD, 0.36% of patients that presented with chest complaints. Compared to ACS patients, TAA/TAD group was older (68.9 vs. 63.2 years), less likely to be diabetic (13% vs 32%), less likely to complain of chest pain (47% vs 85%) and head and neck pain (4% vs 17%). The pain for the TAA/TAD group was less likely characterized as tight/heavy in nature (5% vs 37%). TAA/TAD patients were also less likely to experience shortness of breath (42% vs. 51%), palpitations (2% vs 9%) and dizziness (2% vs 13%) and had a greater incidence of focal lower extremity neurological deficits (6% vs 1%), bradycardia (15% vs. 5%) and tachypnea (53% vs. 22%). On multivariate analysis, increasing heart rate, chest pain, diabetes, head & neck pain, dizziness, and history of myocardial infarction were independent predictors of ACS.ConclusionsIncreasing heart rate, chest pain, diabetes, head & neck pain, dizziness, and history of myocardial infarction can be used to differentiate acute coronary syndromes from thoracic aortic dissections/aneurysms.

Dysphagia lusoria occurs secondary to an aberrant right subclavian artery coursing posterior to the oesophagus. Open ligation and transposition to the right carotid artery via a right supraclavicular approach has been described as a minimally invasive method. However, approaching the origin of the aberrant right subclavian artery through this incision can be extremely challenging. A persistent aberrant right subclavian artery stump may account for postoperative residual dysphagia. This article describes a safe, effective and reproducible surgical approach to dysphagia lusoria due to a non-aneurysmal aberrant right subclavian artery.

The BBTT is an established, safe alternative to blind access for LC. Our technique is simple and rapid and avoids most of the technical difficulties encountered by other open access devices. We believe this method provides surgeons with an option that is efficient and easier to perform than most other conventional open-access laparoscopic techniques.