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

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 (V (max⁡)), complexes II, III, and IV activity (V (succ)), and complex IV activity (V (TMPD)) were analyzed on isolated mitochondria. Lower limb IR decreased significantly lung V (max⁡) (29.4 ± 3.3 versus 24 ± 3.7 μmol O(2)/min/g dry weight, resp.; P = 0.042) and tended to reduce V (succ) and V (TMPD). IR did not modify liver but increased kidneys mitochondrial respiration (79.5 ± 19.9 versus 108.6 ± 21.4, P = 0.035, and 126 ± 13.4 versus 142.4 ± 10.4 μmol O(2)/min/g dry weight for V (max⁡) and V (succ), resp.). Kidneys mitochondrial coupling was increased after IR (6.5 ± 1.3 versus 8.8 ± 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.