FR167653 improves renal recovery and decreases inflammation and fibrosis after renal ischemia reperfusion injury

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

Méthodologie de conception d'un simulateur vidéo laparoscopique. De l'analyse des connaissances á la création des parcours d'apprentissage : Le cas de la chirurgie aortique

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Toward Optimal Learning of the Gesture in Laparoscopic Surgery: Methodology and Performance

International audienceClassical surgical education has to face both a forensic reality and a technical issue: to train a learner in more complex techniques in an increasingly short time. Moreover, surgical training is still based on an empirical hierarchical relationship in which learners must reproduce a sequence of actions in a situation of strong emotional pressure. However, the effectiveness of learning and its quality are linked to the emotional states in which learners find themselves. Among these emotions, epistemic confusion can be found that arises in complex learning situations where there is a cognitive imbalance related to the comprehension of the task, and which results from a rupture between the pre-established patterns of the learner and the new learning task. Although one knows that confusion can have a beneficial or a negative impact on learning, depending on whether it is well regulated or not, the factors that can influence it positively are still poorly understood. Thus, the objective of this experiment is to assess the impact of confusion on the learning of a surgical procedure in an augmented reality context and to determine if this impact varies according to the feedback given to the learners and according to the occurrence of disruptive events. Medical externs were recruited (N = 15) who were required to perform a suturing task on a simulator and whose performance was measured using a Motion Capture (MoCap) system. Even though the statistical analyzes did not allow a conclusion to be reached, the protocol already established makes it possible to consider a longer-term study that will allow (by increasing the number of sessions and the number of participants) more significant results to be obtained in order to develop new surgical learning protocols. This preliminary study opens a new field of research on the influence of epistemic emotions, and more particularly of confusion, which is likely to upset traditional surgical teaching, and is based on negative conditioning and strong emotions with negative valence as well as stress and coercio

Méthodologie de conception d'un simulateur vidéo laparoscopique. De l'analyse des connaissances á la création des parcours d'apprentissage : Le cas de la chirurgie aortique

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Evaluation of different isotypes of vegf in vascular repair during preservation: analysis in a preclinical model

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High-fat diet promotes early vascular remodeling in a renal porcine auto-transplantation model

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