Ischemic preconditioning specifically restores complexes I and II activities of the mitochondrial respiratory chain in ischemic skeletal muscle.
OBJECTIVE
Defective mitochondrial function has been reported in patients presenting with peripheral arterial disease, suggesting it might be an important underlying mechanism responsible for increased morbidity and mortality. We therefore determined the effects of prolonged ischemia on energetic skeletal muscle and investigated whether ischemic preconditioning might improve impaired electron transport chain and oxidative phosphorylation in ischemic skeletal muscle.


METHODS
Thirty rats were divided in three groups: the control group (sham, n = 9) underwent 5 hours of general anesthesia without any ischemia, the ischemia-reperfusion (IR) group (n = 11) underwent 5 hours ischemia induced by a rubber band tourniquet applied on the left root of the hind limb, and in the third group, preconditioning (PC group, n = 10) was performed just before IR and consisted of three cycles of 10 minutes of ischemia, followed by 10 minutes reperfusion. Maximal oxidative capacities (V(max)) of the gastrocnemius muscle and complexes I, II, and IV of the mitochondrial respiratory chain were determined using glutamate-malate (V(max)), succinate (V(s)), and N, N, N,'N'-tetramethyl-p-phenylenediamine dihydrochloride ascorbate as substrates.


RESULTS
Physiologic characteristics were similar in the three groups. Ischemia reduced V(max) by 43% (4.5 +/- 0.4 vs 7.9 +/- 0.5 micromol O(2)/(min x g dry weight), P < .01) and V(s) by 55% (2.9 +/- 0.3 vs 6.3 +/- 0.4 micromol O(2)/min/g dry weight; P < .01) in the IR and sham groups, respectively, and impairments of mitochondrial complexes I and II activities were evident. Of interest was that preconditioning prevented ischemia-induced mitochondrial dysfunction. Both V(max) and V(s) were significantly higher in the PC rats than in IR rats (+32% and +41%, respectively; P < .05), and were not different from sham values.


CONCLUSIONS
Ischemic preconditioning counteracted ischemia-induced impairments of mitochondrial complexes I and II. These data support that ischemic preconditioning might be an interesting approach to reduce muscular injuries in the setting of ischemic vascular diseases.
Thaveau
Fabien
F
Department of Vascular Surgery, Hôpital Civil, Strasbourg, France. fabien.thaveau@chru-strasbourg.fr
Zoll
Joffrey
J
Rouyer
Olivier
O
Chafke
Nabil
N
Kretz
Jean Georges
JG
Piquard
Francois
F
Geny
Bernard
B
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D042967:Electron Transport Complex I / Q000378:metabolism*; D042963:Electron Transport Complex II / Q000378:metabolism*; D007511:Ischemia / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D008931:Mitochondria, Muscle / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000378:metabolism; D018384:Oxidative Stress; D011379:Prognosis; D051381:Rats; D017208:Rats, Wistar