Onset of Adverse Abdominal Events Due to Intestinal Ischemia-Reperfusion Injury after Aortic Cross-Clamping Is Associated with Elevated HSP70 Serum Levels in the Early Postoperative Phase

Tissue injury of the viscera during open thoracoabdominal aortic (TAA) reconstructions has been reported as the aftermath of the ischemia-reperfusion mechanism following supracoeliac aortic cross-clamping. Abdominal complications after open aortic reconstructions, although rare through the intraoperative implementation of selective visceral artery blood perfusion, are associated with high rates of reinterventions and a poor prognosis. Recent animal experiments demonstrated that provoking mesenteric ischemia in rats induces the leukocyte-mediated transcription of heat-shock protein 70 (HSP70), a chaperone belonging to the danger-associated molecular pattern proteins (DAMPs). Translating these findings clinically, we investigated the serum levels of HSP70 in patients undergoing open aortic reconstructions with supracoeliac clamping. We postoperatively observed a relevant induction of HSP70, which remained significantly elevated in cases of postoperative abdominal complications (paralytic ileus, abdominal compartment syndrome, and visceral malperfusion). The receiver–operator curve analysis revealed the reliable prognostic accuracy of HSP70 as a biomarker for these complications as soon as 12 h post-operation (AUC 0.908, sensitivity 88.9%, specificity 83.3%). In conclusion, measuring HSP70 serum levels in the early postoperative phase may serve as a further adjutant in the diagnostic decision making for both the vascular surgeon and intensivist for the timely detection and management of abdominal complications following open TAA surgery

Intraoperative Hemoadsorption (Cytosorb™) during Open Thoracoabdominal Aortic Repair: A Pilot Randomized Controlled Trial

Background: The efficacy of cytokine adsorption in controlling the early inflammation cascade after open thoracoabdominal aortic (TAAA) repair has not been investigated. The aim of this pilot randomized controlled trial was to assess the feasibility and effect of perioperative hemoadsorption during open TAAA repair. Methods: Patients scheduled for open TAAA repair with the use of cardiopulmonary bypass (CPB) were included. The patients were randomized the day before surgery to either intraoperative hemoadsorption during CPB or standard of care. Results: A total of 10 patients were randomly assigned to the intervention group, whereas the control group consisted of 17 patients (mean age of the total cohort, 51.1 ± 11.2 years, 67% male, 3 patients not randomized). The majority of baseline and perioperative characteristics were similar, and no device-related adverse events were reported. A trend to shorter ventilation times in the intervention group was observed (median 88 h vs. 510 h, p = 0.08, Δ422). Severe acute respiratory distress syndrome was significantly less in the intervention patients (p = 0.02). Conclusions: This is the first pilot study showing that the intraoperative use of hemoadsorption in open TAAA repair patients may be feasible and safe, yet larger trials are needed to evaluate whether intraoperative hemoadsorption is associated with improved clinical outcomes

The NephroCheck bedside system for detecting stage 3 acute kidney injury after open thoracoabdominal aortic repair

Abstract Acute kidney injury (AKI) is a common complication after complex aortic procedures and it is associated with relevant mortality and morbidity. Biomarkers for early and specific AKI detection are lacking. The aim of this work is to investigate the reliability of the NephroCheck bedside system for diagnosing stage 3 AKI following open aortic surgery. In this prospective, multicenter, observational study,— https://clinicaltrials.gov/ct2/show/NCT04087161 —we included 45 patients undergoing open thoracoabdominal aortic repair. AKI risk (AKIRisk-Index) was calculated from urine samples at 5 timepoints: baseline, immediately postoperatively and at 12, 24, 48, and 72 h post-surgery. AKIs were classified according to the KDIGO criteria. Contributing factors were identified in univariable and multivariable logistic regression. Predictive ability was assessed with the area under the receiver operator curve (ROCAUC). Among 31 patients (68.8%) that developed AKIs, 21 (44.9%) developed stage-3 AKIs, which required dialysis. AKIs were correlated with increased in-hospital mortality (p = .006), respiratory complications (p < .001), sepsis (p < .001), and multi-organ dysfunction syndrome (p < .001). The AKIRisk-Index showed reliable diagnostic accuracy starting at 24 h post-surgery (ROCAUC: .8056, p = .001). In conclusion, starting at 24 h after open aortic repair, the NephroCheck system showed adequate diagnostic accuracy for detecting the patients at risk for stage 3 AKIs

Combined deficiency in glutathione peroxidase 4 and vitamin E causes multi-organ thrombus formation and early death in mice.

Rationale: Growing evidence indicates that oxidative stress contributes markedly to endothelial dysfunction. The selenoenzyme glutathione peroxidase 4 (Gpx4) is an intracellular antioxidant enzyme important for the protection of membranes by its unique activity to reduce complex hydroperoxides in membrane bilayers and lipoprotein particles. Yet a role of Gpx4 in endothelial cell function has remained enigmatic. Objective: To investigate the role of Gpx4 ablation and subsequent lipid peroxidation in the vascular compartment in vivo. Methods and Results: Endothelial-specific deletion of Gpx4 had no obvious impact on normal vascular homeostasis nor did it impair tumor-derived angiogenesis in mice maintained on a normal diet. By stark contrast, aortic explants from endothelial-specific Gpx4 knockout mice showed a markedly reduced number of endothelial branches in sprouting assays. To shed light onto this apparent discrepancy between the in vivo and ex vivo results, we depleted mice of a second antioxidant, vitamin E, which is normally absent under ex vivo conditions. Mice were therefore fed a vitamin E-depleted diet for 6 weeks before endothelial deletion of Gpx4 was induced by 4-hydroxytamoxifen. Surprisingly, about 80% of the knockout mice died. Histopathological analysis revealed detachment of endothelial cells from the basement membrane as well as endothelial cell death in multiple organs which triggered thrombus formation. Thromboembolic events were the likely cause of various clinical pathologies including heart failure, renal and splenic micro-infarctions or paraplegia. Conclusions: Here we show for the first time that in the absence of Gpx4, sufficient vitamin E supplementation is crucial for endothelial viability