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

Abstract EN

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.