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International audience; AKI is a frequent complication in hospitalized patients. Unfortunately, there is no effective pharmacologic approach for treating or preventing AKI. In rodents, mineralocorticoid receptor (MR) antagonism prevents AKI induced by ischemia-reperfusion (IR). We investigated the specific role of vascular MR in mediating AKI induced by IR. We also assessed the protective effect of MR antagonism in IR-induced AKI in the Large White pig, a model of human AKI. In mice, MR deficiency in smooth muscle cells (SMCs) protected against kidney IR injury. MR blockade by the novel nonsteroidal MR antagonist, finerenone, or genetic deletion of MR in SMCs associated with weaker oxidative stress production. Moreover, ischemic kidneys had higher levels of Rac1-GTP, required for NADPH oxidase activation, than sham control kidneys, and genetic deletion of Rac1 in SMCs protected against AKI. Furthermore, genetic deletion of MR in SMCs blunted the production of Rac1-GTP after IR. Pharmacologic inhibition of MR also prevented AKI induced by IR in the Large White pig. Altogether, we show that MR antagonism, or deletion of the MR gene in SMCs, limited the renal injury induced by IR through effects on Rac1-mediated MR signaling. The benefits of MR antagonism in the pig provide a rational basis for future clinical trials assessing the benefits of this approach in patients with IR-mediated AKI.

To compare the post-operative and mid-term outcomes of laparoscopic aortic surgery with those of conventional aortic surgery performed by a surgical team trained in laparoscopic aortic surgery.A prospective study was conducted between January 2006 and December 2011 with 228 consecutive patients having undergone aortic bypass surgery for either an abdominal aortic aneurysm (n = 139) or occlusive aorto-iliac disease (n = 89). Conventional open aortic surgery was carried out in 145 patients, and total laparoscopic repair in 83 patients. The composite primary end point measure grouped together the following adverse events (AEs): (1) any deaths 30 days or later deaths related to the operation; (2) post-operative hemorrhage necessitating reoperation; (3) myocardial infarction ≤ 30 days; (4) stroke ≤ 30 days; (5) post-operative respiratory failure necessitating re-intubation or assisted ventilation ≥ 4 days; (6) aortic prosthesis infection; (7) aortic prosthesis occlusion; (8) any re-operation related to aortic surgery. In order to diminish bias attributable to the absence of randomization, the two surgical groups were matched by a propensity score enabling analysis of 50 pairs of patients having presented with identical pre-operative characteristics. Univariate analysis of the AE occurring during the first 30 post-operative days was followed by multivariate analysis through logistic regression. The rate of AE during follow up was calculated using the Kaplan-Meier method and the roles of the different co-variables were analyzed using the Cox model.Univariate analysis of the groups adjusted for propensity score showed that laparoscopic repair was associated with a significantly higher risk of AE over the first 30 post-operative days (p = .03). Logistic regression analysis showed that laparoscopic aortic technique (odds ratio [OR] 4.50; p = .01) and coronary artery disease (OR 4.67; p = .02) were independently related to the occurrence of an AE during the post-operative period. The occurrence of AEs during follow up was analyzed using the Cox model. Only two variables, laparoscopic aortic surgery (hazard ratio [HR] 4.40; p = .002) and coronary artery disease (HR 2.70, p = .02), were independently associated with the occurrence of an AE during follow up. The small number of patients included prevented a separate analysis with regard to aneurysmal and occlusive aortic disease.This study suggests that even with a well trained surgical team, the laparoscopic approach increases the risk for AEs observed in the course of aortic surgery. ClinicalTrials.gov Identifier: NCT02325700.

Objective The purpose of this article was to report our experience of the repair of renal artery restenosis after percutaneous transluminal renal angioplasty (PTRA) using a total laparoscopic technique without robotic assistance. Methods Between February 2005 and October 2009, we performed six total laparoscopic aortorenal artery bypasses for restenosis after failed PTRA. All these patients had recurrent hypertension with renal insufficiency. Results The mean operative time was 246 minutes (range, 200-310 minutes). The mean warm renal ischemic time was 28 minutes (range, 22-35 minutes). All patients received a prosthetic graft interposition. The estimated surgical blood loss was 980 mL (range, 500-1400 mL). No conversion was observed and no in-hospital deaths occurred. There was no severe postoperative morbidity. Postoperative serum creatinine levels raised in all patients but all returned to baseline before discharge. Median length of postoperative hospital stay was 6 days (range, 4-8 days). Median follow-up was 13 months (range, 7-19 months). Color Doppler ultrasound scan examination and computed tomography (CT) with injection of contrast media showed patency of all bypasses. Hypertension was improved in all patients but renal insufficiency remained unchanged. Conclusion Total laparoscopic renal artery bypass is feasible and safe in patients after failed PTRA. This approach may reduce the morbidity of open repair but is technically demanding and necessitates a large previous experience in total laparoscopic aortic surgery.

Objectives Carotid endarterectomy (CEA) is the standard treatment for atherosclerotic lesions involving the carotid bifurcation. However, CEA can be challenging under some conditions. The goal of this study was to determine the outcome and durability of prosthetic carotid bypass grafting (PCB) with polytetrafluoroethylene (PTFE) grafts as an alternative to CEA. Methods This is a prospective series of 198 consecutive patients with PCB, representing 12.4% of 1595 patients with a carotid reconstruction procedure performed in our department between September 1986 and December 2006. Qualifying event was stroke in 67 patients (34%) and transient ischaemic attack (TIA) in 45 (23%), and 86 patients (43%) were asymptomatic. Primary indications for PCB were extensive atherosclerotic lesions ( n = 71; 36%), carotid stenosis associated with kinking ( n = 49; 25%), recurrent stenosis ( n = 47; 23%), stenosis after radiation therapy ( n = 18; 9%) and technical failure of CEA ( n = 13; 7%), with excessive arterial wall thinning and perforation after endarterectomy ( n = 10) or intimal flap on completion digital angiography ( n = 3). Results The combined stroke and death rate at 30 days were 0.5% (one stroke). Median follow-up was 9.5 years (interquartile range (IQR): 6.2–18.3 years). At 10 years, primary patency was 97.9 ± 3.4%. Six PCBs (3.0%) became occluded during follow-up; one patient had a restenosis greater than 50% and 18 patients (9.1%) had a restenosis of less than 50%. Five patients had an ipsilateral stroke (one postoperative stroke, one at 103 days with a patent PCB and three related to occlusion of the PCB at 4, 13 and 15 years after the procedure). At 10 years, cumulative stroke-free survival was 98.4 ± 3.2%, and cumulative survival was 78.8 ± 7.0%. Conclusions PCB is a safe surgical alternative and is durable, with a low incidence of graft restenosis, when CEA seems hazardous.

Background It was demonstrated that postischemic kidney expresses different factors in a pattern that recapitulates expression of these factors in the developing kidney. We investigated whether peripheral-type benzodiazepine receptor (PBR), which belongs to the mitochondrial permeability transition pore and is essential during development, could be influenced by the ischemia-reperfusion injury process when compared with leukemia inhibitor factor (LIF). Study design PBR, LIF, and LIF receptor messengers and proteins were analyzed in adult normal and ischemic kidney under conditions mimicking cardiac arrest: 18 pigs were studied after 60 minutes of warm ischemia and reperfusion for 7 days and compared with sham-operated (Sham, n=12) and control (CONT, n=12) groups. The same messengers and proteins were assessed in fetal kidneys. Results In normal kidney, PBR was expressed in descending and ascending limbs of Henle and in distal tubules. After ischemia-reperfusion injury, PBR mRNA significantly increased between days 1 and 7 in cortex and outer medulla. PBR protein increased between days 1 and 7, and was transiently expressed in proximal tubules at days 1 and 3 and returned to basal level at day 7. LIF messenger and protein increased rapidly at day 1 in proximal tubules. In turn, LIF receptor messenger and protein were not changed during reperfusion. Conclusions These results suggest that PBR may be implicated in ischemia-reperfusion injury and, particularly, in the regenerative process within proximal tubules with LIF. These new insights open the possibility of novel targets for organ protection and repair.

This retrospective study aims to clarify the mechanisms, frequency, symptoms, treatment, and outcome of post-traumatic thoracic outlet syndromes. A total of 13 patients (7 men and 6 women) with a mean age of 41 +/- 16 years were studied. Underlying injuries resulted from sports, road, and household accidents. Bone lesions were pseudarthrosis, hypertrophic callus, and luxations. Congenital anomalies were observed in five patients (38%). Vascular lesions included aneurysm of the subclavian artery or vein, acute ischemia, and subclavian vein thrombosis. Operative treatment involving orthopedic and/or vascular surgery was indicated in all patients. Post-traumatic thoracic outlet syndrome occurs in young subjects after violent trauma. Vascular complications are frequent and severe. Treatment achieves good results but benefits may be diminished by bone or nerve involvement.

Objectives The study aims to assess the feasibility and midterm outcome of trans-peritoneal laparoscopy for coeliac artery compression syndrome (CACS). Design Retrospective chart review involving four European vascular surgery departments and two surgical teams. Materials and methods charts for patients who underwent laparoscopy for symptomatic CACS between December 2003 and November 2009 were reviewed. Preoperative computed tomography (CT) angiography and postoperative duplex scan and/or CT angiography were performed. Results Eleven consecutive patients (nine women) with a median age of 52 years (interquartile range: 42.5–59 years) underwent trans-peritoneal laparoscopy for CACS. All patients had a history of postprandial abdominal pain; weight loss exceeded 10% of the body mass in eight cases. Preoperative CT angiography revealed coeliac trunk stenosis >70% in all cases. One patient had additional aortitis and inferior mesenteric artery occlusion, while another patient presented with an occluded superior mesenteric artery. Two conversions occurred (one difficult dissection and one aorto-hepatic bypass needed for incomplete release of CACS). The median blood loss was 195 ml (range: 50–900 ml) and median operative time was 80 min (interquartile range: 65–162.5 years). Symptoms improved immediately in 10/11 patients (no residual stenosis) while one remained unchanged despite a residual stenosis treated by a percutaneous angioplasty. Symptoms reappeared in one patient due to coeliac axis occlusion. The mean follow-up period was 35 ± 23 months (range: 12–78 months). Conclusion Our study demonstrates that trans-peritoneal laparoscopy for treating median arcuate ligament syndrome is safe and feasible. Additional patients and a longer follow-up are needed for long-term assessment of this laparoscopic technique.

International audience; Ischemia reperfusion injury (IRI) is pivotal for renal fibrosis development via peritubular capillaries injury. Coagulation represents a key mechanism involved in this process. Melagatran (R) (M), a thrombin inhibitor, was evaluated in an autotransplanted kidney model, using Large White pigs. To mimic deceased after cardiac death donor conditions, kidneys underwent warm ischemia (WI) for 60 min before cold preservation for 24 h in University of Wisconsin solution. Treatment with M before WI and/or in the preservation solution drastically improved survival at 3 months, reduced renal dysfunction related to a critical reduction in interstitial fibrosis, measured by Sirius Red staining. Tissue analysis revealed reduced expression of transforming growth factor-beta (TGF-beta) and activation level of its effectors phospho-Smad3, Smad4 and connective tissue growth factor (CTGF) after M treatment. Fibrinolysis activation was also observed, evidenced by downregulation of PAI-1 protein and gene expression. In addition, M reduced S100A4 expression and vimentin staining, which are markers for epithelial mesenchymal transition, a major pathway to chronic kidney fibrosis. Finally, expression of oxidative stress markers Nox2 and iNOS was reduced. We conclude that inhibition of thrombin is an effective therapy against IRI that reduces chronic graft fibrosis, with a significantly positive effect on survival.

The peripheral benzodiazepine receptor (PBR) is located mainly in the outer mitochondrial membrane and many functions are associated directly or indirectly with the PBR. We have studied the influence of different durations of warm ischemia (WI) on renal function, tissue damage and PBR expression in a Large Whitepig model. After a midline incision, the renal pedicle was clamped for 10 (WI10), 30 (WI30), 45 (WI45), 60 (WI60) or 90 min (WI90), and blood and renal tissue samples were collected between 1 day and 2 weeks after reperfusion for assessment of renal function. Metabolite excretion associated with renal ischemia reperfusion injury such as trimethylamine-N-oxide (TMAO) was quantified in blood by magnetic resonance spectroscopy. PBR mRNA and protein expression were determined in renal tissue. TMAO levels rose progressively and significantly with increasing duration of WI. PBR mRNA expression was upregulated between 3 h and 1 day after reperfusion in WI30, WI45 and WI60. Its upregulation was noted 3 days after reperfusion in WI90. At day 14, PBR transcript expression was not different from basal level in any group. PBR protein followed the same pattern. These findings suggest a new role for PBR which could be a major target in the regeneration process during ischemia reperfusion.

Objectives To analyze the outcome of our preliminary experience with total laparoscopic aortic repair in patients with occlusive or aneurysmal disease. Material and methods From September 2002 to April 2005, we performed 95 consecutive total laparoscopic aortic repair procedures including 72 for aortic occlusive disease (group A) and 23 for abdominal aortic aneurysm (group B). Results In group A, mean operating time was 216±50 min with a mean clamp time of 57±21 min and surgical conversion was required in two cases (2.7%). No postoperative death occurred but there were three postoperative complications necessitating re-intervention (retroperitoneal hematoma, embolic ischemia, and early prosthetic infection). Mean duration of hospitalization was 8 days (range, 5–42 days). All grafts were patent at 2 months. In group B, mean operating time was 251±57 min with a mean clamp time of 101±15 min and surgical conversion was required in seven cases (30%). There was one postoperative death (4.3%) due to pulmonary embolism and one non-fatal complication (retroperitoneal hematoma). Mean duration of hospitalization was 6.4 days (range, 4–12 days). All grafts were patent at 2 months. Conclusion Total laparoscopic repair is feasible and safe for occlusive and aneurysmal aortic disease. Operators must acquire technical skills using simulators.

ObjectiveAcute tubular necrosis (ATN) secondary to induced warm ischemia (WI) results in inflammatory and delayed fibrotic processes and remains a common clinical problem with serious consequences. Because tumor necrosis factor-α (TNF-α) is a prominent proinflammatory factor implicated in the pathophysiology of acute renal ischemia reperfusion injury (IRI), we hypothesized that FR167653 (FR), a potent inhibitor of TNF-α and interleukin-1β production, may reduce IRI.MethodsIRI was induced in male pigs by bilateral clamping of the renal pedicle for 90 minutes (WI90), or unilateral renal clamping (90 minutes) after contralateral nephrectomy (1/2N×90), or unilateral renal clamping without contralateral nephrectomy (WIuni90). FR was administered intravenously 60 minutes before WI (1 mg/kg/h), during WI, and continuously for 3 hours (1 mg/kg/h) during reperfusion in treated groups (FRWI90, FR1/2N×90, or FRWIuni90). Blood and urine samples were collected between day 1 and 3 months after reperfusion for assessment of renal function. Kidneys were excised and renal tissues were collected at 3 months for morphologic and inflammation evaluation and protein analysis. Experimental groups were compared with sham operated (control) and heminephrectomized (Unif) groups without renal ischemia.ResultsThree WI90 animals (43%) and five 1/2N×90 (70%) were euthanized and necropsied at day 7 because of no urine production or poor conditions. Mortality was significantly improved after FR treatment. Survival was 100% in the control, Unif, WIuni90, and FR groups. In Unif groups, FR significantly reduced renal failure and bilateral renal ischemia (P < .05). At 3 months, proteinuria was significantly reduced in FR-treated groups (P < .01). Inflammatory cells count was also dramatically diminished in FR-treated pigs (P < .01 for CD3-positive cells). The second aspect of transient ischemia is the fibrotic process determined at 3 months. FR treatment was characterized by a reduction of renal fibrosis, particularly in Unif groups. TNF-α protein expression was diminished in FR-treated groups.ConclusionThis is the first evidence that FR reduced the early and long-term effect of WI in the severe ischemia model. This effect was particularly marked against fibrosis and inflammation, which would contribute to deterioration of a patient's renal function.Clinical RelevanceAcute ischemia of the kidney is common in the setting of renal artery or aortic surgery. Deterioration in renal function is a common cause of morbidity in patients treated surgically for juxtarenal and suprarenal abdominal aortic aneurysms. FR167653 represents a useful therapeutic approach to prevent renal damage in a planned period of warm ischemia and during suprarenal aortic surgery.

Background The purpose of this study was to assess the overall short-term outcome of stent-graft repair for thoracic aortic disease in France between June 1999 and May 2001. Methods This retrospective study was designed by the French National Health Insurance Fund for Salaried Workers. To ensure objectivity, data were retrieved at each center and checked by a team of medical advisors. Results Between June 1999 and May 2001, a total of 166 stent-graft repairs for thoracic aortic disease were performed in 166 patients, mainly by surgeons in the operating room (88%). Patients were classified according to the American Society of Anesthesiologists as status I or II in 24% of cases, status III in 56%, and status IV or V in 20%. The diameter of the thoracic aneurysm was less than 50 mm in 17% of cases. Seventeen patients (10%) died during the first 3 months, including 8 within the first 30 days after the procedure. A total of 49 complications were noted in 34 patients (20.5%). Endoleaks occurred in 27 patients (16.3%), including 8 that necessitated further treatment. Other stent-related complications included rupture (n = 3), aortoesophageal or tracheal fistula (n = 3), paraplegia (n = 6), stent migration (n = 2), visceral embolism (n = 5), and cerebral embolism (n = 2). There were 14 delivery-related complications (8%) at the catheterization site. Non–stent-related complications occurred in 14 (8%). Conclusions This nationwide study demonstrates that stent-graft repair for thoracic aortic disease can be performed with acceptable postoperative morbidity. However, it is not a risk-free procedure and should continue to be used in an investigative setting.