Isoflurane Anesthesia Preserves Liver and Lung Mitochondrial Oxidative Capacity After Gut Ischemia-Reperfusion
Pôle Anesthésie Réanimation Chirurgicale, SAMU, Hôpitaux Universitaires de Strasbourg, Avenue Molière, 67098 Strasbourg, France. Anesthesia and analgesia
(Impact Factor: 3.47).
11/2011; 113(6):1438-41. DOI: 10.1213/ANE.0b013e3182367a10
Lung and liver dysfunction is involved in gut ischemia-reperfusion (IR)-induced multiple organ failure. We compared the effects of ketamine and isoflurane on liver and lung mitochondrial oxidative capacity after gut IR.
Adult male Wistar rats were randomized into 4 groups (controls and gut IR receiving either intraperitoneal ketamine or inhaled isoflurane). Maximal oxygen consumption and the activity of respiratory chain complexes were measured on isolated liver and lung mitochondria.
Gut IR significantly impaired liver and lung mitochondrial oxidative capacity when using ketamine but not isoflurane.
Isoflurane preserved liver and lung mitochondrial oxidative capacity after gut IR.
Available from: Jamal Bouitbir
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ABSTRACT: OBJECTIVES: Mesenteric ischaemia/reperfusion (IR) may lead to liver mitochondrial dysfunction and multiple organ failure. We determined whether gut IR induces early impairment of liver mitochondrial oxidative activity and whether methylene blue (MB) might afford protection. DESIGN: Controlled animal study. MATERIALS AND METHODS: Rats were randomised into three groups: controls (n = 18), gut IR group (mesenteric ischaemia (60 min)/reperfusion (60 min)) (n = 18) and gut IR + MB group (15 mg kg(-1) MB intra-peritoneally) (n = 16). Study parameters were: serum liver function markers, blood lactate, standard histology and DNA fragmentation (apoptosis) on intestinal and liver tissue, maximal oxidative capacity of liver mitochondria (state 3) and activity of complexes II, III and IV of the respiratory chain measured using a Clark oxygen electrode. RESULTS: Gut IR increased lactate deshydrogenase (+982%), aspartate and alanine aminotransferases (+43% and +74%, respectively) and lactate levels (+271%). It induced segmental loss of intestinal villi and cryptic apoptosis. It reduced liver state 3 respiration by 30% from 50.1 ± 3 to 35.2 ± 3.5 μM O(2) min(-1) g(-1) (P < 0.01) and the activity of complexes II, III and IV of the mitochondrial respiratory chain. Early impairment of liver mitochondrial respiration was related to blood lactate levels (r(2) = 0.45). MB restored liver mitochondrial function. CONCLUSIONS: MB protected against gut IR-induced liver mitochondria dysfunction.
European journal of vascular and endovascular surgery: the official journal of the European Society for Vascular Surgery 12/2012; 45(2). DOI:10.1016/j.ejvs.2012.11.011 · 2.49 Impact Factor
Available from: Izzie Jacques Namer
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ABSTRACT: The aim of this study was to assess the functional preservation of the lung graft with anterograde lung perfusion in a model of donation after cardiac death. Thirty minutes after cardiac arrest, in situ anterograde selective pulmonary cold perfusion was started in six swine. The alveolo-capillary membrane was challenged at 3, 6, and 8 h with measurements of the mean pulmonary arterial pressure (mPAP), the pulmonary vascular resistance (PVR), the PaO2 /FiO2 ratio, the transpulmonary oxygen output (tpVO2 ), and the transpulmonary CO2 clearance (tpCO2 ). Mitochondrial homeostasis was investigated by measuring maximal oxidative capacity (Vmax ) and the coupling of phosphorylation to oxidation (ACR, acceptor control ratio) in lung biopsies. Inflammation and induction of primary immune response were assessed by measurement of tumor necrosis factor alpha (TNFα), interleukine-6 (IL-6) and receptor for advanced glycation endproducts (RAGE) in bronchoalveolar lavage fluid. Data were compared using repeated measures Anova. Pulmonary hemodynamics (mPAP: P = 0.69; PVR: P = 0.46), oxygenation (PaO2 /FiO2 : P = 0.56; tpVO2 : P = 0.46), CO2 diffusion (tpCO2 : P = 0.24), mitochondrial homeostasis (Vmax : P = 0.42; ACR: P = 0.8), and RAGE concentrations (P = 0.24) did not significantly change up to 8 h after cardiac arrest. TNFα and IL-6 were undetectable. Unaffected pulmonary hemodynamics, sustained oxygen and carbon dioxide diffusion, preserved mitochondrial homeostasis, and lack of inflammation suggest a long-lasting functional preservation of the graft with selective anterograde in situ pulmonary perfusion.
Transplant International 07/2013; 26(10). DOI:10.1111/tri.12157 · 2.60 Impact Factor
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ABSTRACT: Gut ischemia reperfusion (IR) is thought to trigger systemic inflammation, multiple organ failure, and death. The aim of this study was to investigate inflammatory responses in blood and in two target organs after gut IR.
This was a controlled animal study. Adult male Wistar rats were randomized into two groups of eight rats: control group and gut IR group (60 minutes of superior mesenteric artery occlusion followed by 60 minutes of reperfusion). Lactate and four cytokines (tumor necrosis factor-α, interleukin [IL]-1β, IL-6, and IL-10) were measured in mesenteric and systemic blood. The relative gene expression of these cytokines was determined by real time polymerase chain reaction in the gut, liver, and lung.
Gut IR significantly increased lactate levels in mesenteric (0.9 ± 0.4 vs. 3.7 ± 1.8 mmol/L; p < .001) and in systemic blood (1.3 ± 0.2 vs. 4.0 ± 0.3 mmol/L; p < .001). Gut IR also increased the levels of four cytokines in mesenteric and systemic blood. IL-6 and IL-10 were the main circulating cytokines; there were no significant differences between mesenteric and systemic cytokine levels. IL-10 was upregulated mainly in the lung, suggesting that this organ could play a major role during gut reperfusion.
The predominance of IL-10 over other cytokines in plasma and the dissimilar organ responses, especially of the lung, might be a basis for the design of therapies, for example lung protective ventilation strategies, to limit the deleterious effects of the inflammatory cascade. A multi-organ protective approach might involve gut directed therapies, protective ventilation, hemodynamic optimization, and hydric balance.
Copyright © 2014 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.
European Journal of Vascular and Endovascular Surgery 12/2014; 49(1). DOI:10.1016/j.ejvs.2014.10.022 · 2.49 Impact Factor
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