Remote Effects of Lower Limb Ischemia-Reperfusion: Impaired Lung, Unchanged Liver, and Stimulated Kidney Oxidative Capacities

Author:

Mansour Z.12,Charles A. L.13,Kindo M.12,Pottecher J.1,Chamaraux-Tran T. N.1,Lejay A.1,Zoll J.13,Mazzucotelli J. P.12,Geny B.13

Affiliation:

1. Equipe d’Accueil 3072 “Mitochondries, Stress Oxydant et Protection Musculaire”, Fédération de Médecine Translationnelle, Institut de Physiologie, Universite de Strasbourg, 67000 Strasbourg, France

2. Service de Chirurgie Cardiovasculaire, Pole de Cardiologie, Hopitaux Universitaires, CHRU de Strasbourg, 67000 Strasbourg, France

3. Service de Physiologie et d’Explorations Fonctionnelles, Pole de Pathologie Thoracique, Hopitaux Universitaires, CHRU de Strasbourg, 67000 Strasbourg, France

Abstract

Remote organ impairments are frequent and increase patient morbidity and mortality after lower limb ischemia-reperfusion (IR). We challenged the hypothesis that lower limb IR might also impair lung, renal, and liver mitochondrial respiration. Two-hour tourniquet-induced ischemia was performed on both hindlimbs, followed by a two-hour reperfusion period in C57BL6 mice. Lungs, liver and kidneys maximal mitochondrial respiration (Vmax), complexes II, III, and IV activity (Vsucc), and complex IV activity (VTMPD) were analyzed on isolated mitochondria. Lower limb IR decreased significantly lungVmax(29.4±3.3versus24±3.7μmol O2/min/g dry weight, resp.;P=0.042) and tended to reduceVsuccandVTMPD. IR did not modify liver but increased kidneys mitochondrial respiration (79.5±19.9versus108.6±21.4,P=0.035, and126±13.4versus142.4±10.4μmol O2/min/g dry weight forVmaxandVsucc, resp.). Kidneys mitochondrial coupling was increased after IR (6.5±1.3versus8.8±1.1,P=0.008). There were no histological changes in liver and kidneys. Thus, lung mitochondrial dysfunction appears as a new early marker of hindlimb IR injuries in mice. Further studies will be useful to determine whether enhanced kidneys mitochondrial function allows postponing kidney impairment in lower limb IR setting.

Publisher

Hindawi Limited

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine

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