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 (Vmax⁡), complexes II, III, and IV activity (Vsucc), and complex IV activity (VTMPD) were analyzed on isolated mitochondria. Lower limb IR decreased significantly lung Vmax⁡ (29.4±3.3 versus 24±3.7 μmol O2/min/g dry weight, resp.; P=0.042) and tended to reduce Vsucc and VTMPD. 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 O2/min/g dry weight for Vmax⁡ and Vsucc, 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.