Effect of postconditioning on mitochondrial dysfunction in experimental aortic cross-clamping.
BACKGROUND
Cross-clamping of the aorta during abdominal aortic aneurysm surgery induces muscle ischaemia with resultant morbidity. This study tested whether ischaemic postconditioning would decrease mitochondrial dysfunction in skeletal muscle by reducing oxidative stress.


METHODS
Three groups (9 rats each) underwent surgery, including a control group without ischaemia and an ischaemia-reperfusion group that had 3 h ischaemia induced by aortic clamping and collateral vessel ligation, followed by 2 h of reperfusion. The third group had ischaemia for 3 h then underwent postconditioning comprising three short intervals of ischaemia-reperfusion at the onset of reperfusion. Activity of complexes I, II, III and IV of the mitochondrial respiratory chain was monitored in gastrocnemius muscle, along with oxidative stress measured by dihydroethidium (DHE) staining and antioxidant defence determined by measurement of glutathione levels.


RESULTS
Ischaemia-reperfusion alone caused a significant reduction in maximal oxidative capacity (-31.8 per cent; P = 0.002), activity of complexes II, III and IV (-34.5 per cent; P = 0.007) and complex IV activity (-30.6 per cent; P = 0.039). It also increased reactive oxygen species (DHE staining increased to 223.1 per cent of control value; P = 0.027) and reduced antioxidant defence (glutathione level -28.6 per cent; P = 0.039). Postconditioning counteracted these deleterious effects by increasing mitochondrial complex I, II, III and IV activities, restoring muscle DHE staining and preserving glutathione content.


CONCLUSIONS
Ischaemic postconditioning protects skeletal muscle mitochondria against ischaemia-reperfusion injury by reducing oxidative stress and preserving antioxidant defence in an experimental model. Mitochondrial protection to reduce reperfusion injury in clinical vascular surgery may be warranted.
Service de Physiologie et d'Explorations Fonctionnelles, Pôle de Pathologie Thoracique, Hôpitaux Universitaires, Centre Hospitalier Régional Universitaire Strasbourg, Strasbourg, France.
A-L
AL
Charles
A-S
AS
Guilbert
J
J
Bouitbir
P
P
Goette-Di Marco
I
I
Enache
J
J
Zoll
F
F
Piquard
B
B
Geny
D000704:Analysis of Variance; D000818:Animals; D001011:Aorta; D003250:Constriction; D005979:Glutathione Peroxidase / Q000378:metabolism; D057775:Ischemic Postconditioning; D008297:Male; D028361:Mitochondrial Diseases / Q000517:prevention & control*; D018482:Muscle, Skeletal / Q000098:blood supply*; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000517:prevention & control*
D017382:Reactive Oxygen Species; D005979:Glutathione Peroxidase