Gut dysbiosis is associated with acceleration of lupus nephritis.

The gut microbiota (GM) exerts a strong influence over the host immune system and dysbiosis of this microbial community can affect the clinical phenotype in chronic inflammatory conditions. To explore the role of the GM in lupus nephritis, we colonized NZM2410 mice with Segmented Filamentous Bacteria (SFB). Gut colonization with SFB was associated with worsening glomerulonephritis, glomerular and tubular immune complex deposition and interstitial inflammation compared to NZM2410 mice free of SFB. With SFB colonization mice experienced an increase in small intestinal lamina propria Th17 cells and group 3 innate lymphoid cells (ILC3s). However, although serum IL-17A expression was elevated in these mice, Th17 cells and ILC3s were not detected in the inflammatory infiltrate in the kidney. In contrast, serum and kidney tissue expression of the macrophage chemoattractants MCP-1 and CXCL1 were significantly elevated in SFB colonized mice. Furthermore, kidney infiltrating F4/80+CD206+M2-like macrophages were significantly increased in these mice. Evidence of increased gut permeability or "leakiness" was also detected in SFB colonized mice. Finally, the intestinal microbiome of SFB colonized mice at 15 and 30 weeks of age exhibited dysbiosis when compared to uncolonized mice at the same time points. Both microbial relative abundance as well as biodiversity of colonized mice was found to be altered. Collectively, SFB gut colonization in the NZM2410 mouse exacerbates kidney disease, promotes kidney M2-like macrophage infiltration and overall intestinal microbiota dysbiosis.

Performance of a novel temporary arterial shunt in a military-relevant controlled hemorrhage swine model.

BACKGROUND: In military trauma, temporary vascular shunts restore arterial continuity until delayed vascular reconstruction, often for a period of hours. A novel US Air Force-developed trauma-specific vascular injury shunt (TS-VIS) incorporates an accessible side port for intervention or monitoring, which may improve patency under adverse hemodynamic conditions. Our objective was to evaluate TS-VIS patency in the setting of volume-limited resuscitation from hemorrhagic shock. METHODS: Female swine (70-90 kg) underwent 30% hemorrhage and occlusion of the left external iliac artery for 30 minutes. Animals were allocated to one of three groups (n = 5 per group) by left external iliac artery treatment: Sundt shunt (SUNDT), TS-VIS with arterial pressure monitoring (TS-VIS), or TS-VIS with heparin infusion (10 µ/kg per hour, TS-VISHep). Animals were resuscitated with up to 3 U of whole blood to maintain a mean arterial pressure (MAP) of >60 mm Hg and were monitored for 6 hours. Bilateral femoral arterial flow was continuously monitored with transonic flow probes, and shunt thrombosis was defined as the absence of flow for greater than 5 minutes. RESULTS: No intergroup differences in MAP or flow were observed at baseline or following hemorrhage. Animals were hypotensive at shunt placement (MAP, 35.5 ± 7.3 mm Hg); resuscitation raised MAP to >60 mm Hg by 26.5 ± 15.5 minutes. Shunt placement required 4.5 ± 1.8 minutes with no difference between groups. Four SUNDT thrombosed (three before 60 minutes). One SUNDT thrombosed at 240 minutes, and two TS-VIS and one TS-VISHep thrombosed between 230 and 282 minutes. Median patency was 21 minutes for SUNDT and 360 minutes for both TS-VIS groups (p = 0.04). While patent, all shunts maintained flow between 60% and 90% of contralateral. CONCLUSION: The TS-VIS demonstrated sustained patency superior to the Sundt under adverse hemodynamic conditions. No benefit was observed by the addition of localized heparin therapy over arterial pressure monitoring by the TS-VIS side port.

Conversion of the Abdominal Aortic and Junctional Tourniquet (AAJT) to Infrarenal Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) Is Practical in a Swine Hemorrhage Model.

BACKGROUND: Two methods of controlling pelvic and inguinal hemorrhage are the Abdominal Aortic and Junctional Tourniquet (AAJT; Compression Works) and resuscitative endovascular balloon occlusion of the aorta (REBOA). The AAJT can be applied quickly, but prolonged use may damage the bowel, inhibit ventilation, and obstruct surgical access. REBOA requires technical proficiency but avoids many of the complications associated with the AAJT. Conversion of the AAJT to REBOA would allow for field hemorrhage control with mitigation of the morbidity associated with prolonged AAJT use. METHODS: Yorkshire male swine (n = 17; 70-90kg) underwent controlled 40% hemorrhage. Subsequently, AAJT was placed on the abdomen, midline, 2cm superior to the ilium, and inflated. After 1 hour, the animals were allocated to an additional 30 minutes of AAJT inflation (continuous AAJT occlusion [CAO]), REBOA placement with the AAJT inflated (overlapping aortic occlusion [OAO]), or REBOA placement following AAJT removal (sequential aortic occlusion [SAO]). Following removal, animals were observed for 3.5 hours. RESULTS: No statistically significant differences in survival, blood pressure, or laboratory values were found following intervention. Conversion to REBOA was successful in all animals but one in the OAO group. REBOA placement time was 4.3 ± 2.9 minutes for OAO and 4.1 ± 1.8 minutes for SAO (p = .909). No animal had observable intestinal injury. CONCLUSIONS: Conversion of the AAJT to infrarenal REBOA is practical and effective, but access may be difficult while the AAJT is applied.

Effect of the Abdominal Aortic and Junctional Tourniquet on chest compressions in a swine model of ventricular fibrillation.

INTRODUCTION: Mortality for out-of-hospital cardiac arrest is high when traditional chest compressions are used without adjuncts. The abdominal aortic and junctional tourniquet (AAJT) is a device with a wedge-shaped air bladder that occludes the aortic bifurcation, augmenting blood flow to the heart and brain. Previously, the addition of AAJT during chest compression led to an increase in rate of survival in a model of traumatic cardiac arrest. HYPOTHESIS: This study was designed to determine if application of the AAJT would lead to more effective chest compressions as measured by improved hemodynamic parameters and an increased rate of return of spontaneous circulation (ROSC). METHODS: Yorkshire swine (n = 6 per group) underwent general anesthesia and instrumentation. Ventricular fibrillation (Vfib) was electrically induced and animals were allocated into groups with or without the AAJT. The AAJT was inflated if selected after four minutes of compressions. Following a total of ten minutes of compressions, the animals entered into a ten-minute advanced cardiac life support phase. Hemodynamics and blood gas measurements were compared between groups. RESULTS: ROSC or cardioversion from Vfib was not achieved in either group. The AAJT group had improved hemodynamic parameters with significantly higher carotid diastolic pressure and higher blood flow in the carotid artery (p = 0.016 and 0.028 respectively). However, no significant differences were observed with coronary perfusion pressure or end tidal CO2. CONCLUSION: The AAJT did not confer a survival advantage during chest compressions, but hemodynamic improvements were observed while the AAJT was in place.