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 (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 O2/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 O2/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.
Highlights
Peripheral arterial disease is a frequent pathology and corresponds to a major public health problem
Reducing oxidative stress and skeletal muscle mitochondrial dysfunction becomes a major goal in the setting of lower limb ischemia-reperfusion (IR) [2, 3]
The main results of this study are to demonstrate for the first time that tourniquet-induced bilateral hindlimb ischemiareperfusion (1) impairs lung maximal oxidative capacity, (2) does not modify liver mitochondrial function, and (3) unexpectedly stimulates kidney mitochondrial respiratory chain complexes activities and coupling in experimental mice
Summary
Peripheral arterial disease is a frequent pathology and corresponds to a major public health problem. A better knowledge on ischemia and reperfusion-specific deleterious effects results in new therapies able to reduce skeletal muscle mitochondrial dysfunctions such as ischemic and/or pharmacologic pre- or postconditioning. Reducing oxidative stress and skeletal muscle mitochondrial dysfunction becomes a major goal in the setting of lower limb ischemia-reperfusion (IR) [2, 3]. Even subtle muscle damage can lead to significant remote organ injuries, and, improving our knowledge on the mechanisms involved in such lesions appears mandatory. Lower limb ischemia-reperfusion is well known to result in remote organ injuries, key factors increasing perioperative and long-term morbidities [4,5,6,7,8]
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