Remote and local ischemic preconditioning equivalently protects rat skeletal muscle mitochondrial function during experimental aortic cross-clamping

• Published in: Journal of vascular surgery 2012-02, Vol.55 (2), p.497-505.e1
• Main Authors: Mansour, Ziad, MD, MS, Bouitbir, Jamal, PhD, Charles, Anne Laure, PhD, Talha, Samy, MD, Kindo, Michel, MD, Pottecher, Julien, MD, Zoll, Joffrey, PhD, Geny, Bernard, MD, PhD
• Format: Article
• Language: English
• Subjects: Anesthesia; Anesthesia depending on type of surgery; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Aorta, Abdominal - surgery; bcl-2-Associated X Protein - genetics; Biological and medical sciences; Cell Respiration; Constriction; Cytoprotection; Disease Models, Animal; Electron Transport Chain Complex Proteins - metabolism; Energy Metabolism; Glutathione - metabolism; Glutathione Peroxidase - genetics; Hindlimb; Ischemic Preconditioning - methods; Male; Medical sciences; Mitochondria, Muscle - metabolism; Mitochondria, Muscle - pathology; Muscle, Skeletal - blood supply; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Proto-Oncogene Proteins c-bcl-2 - genetics; Rats; Rats, Wistar; Real-Time Polymerase Chain Reaction; Reperfusion Injury - metabolism; Reperfusion Injury - pathology; Reperfusion Injury - prevention & control; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Superoxide Dismutase - genetics; Superoxide Dismutase - metabolism; Superoxide Dismutase-1; Surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Thoracic and cardiovascular surgery. Cardiopulmonary bypass; Time Factors; Vascular surgery: aorta, extremities, vena cava. Surgery of the lymphatic vessels; Vascular Surgical Procedures - adverse effects
• ISSN: 0741-5214; 1097-6809
• DOI: 10.1016/j.jvs.2011.07.084

Objective This study investigated whether remote (rIPC) and local ischemic preconditioning (IPC) similarly limit skeletal muscle dysfunction induced by aortic cross-clamping. Methods Rats were divided in three groups: the sham-operated control group (C) underwent surgery without clamping. The ischemia-reperfusion group (IR) had 3 hours of ischemia induced by aortic clamping and collateral vessels ligation, followed by 2 hours of reperfusion. The IPC group had, before prolonged ischemia, three bouts of 10 minutes of ischemia and 10 minutes of reperfusion on the right hind limb. Thus, right hind limbs had local IPC and left hind limbs had rIPC. Complexes I, II, III, and IV activities of the mitochondrial respiratory chain of the gastrocnemius muscle were measured using glutamate-malate (Vmax ), succinate (Vsucc ), and N,N,N′,N′-tetramethyl-p-phenylenediamine dihydrochloride (TMPD)-ascorbate (VTMPD ). Expressions of genes involved in apoptosis ( Bax , Bcl-2 ) and antioxidant defense (superoxide dismutase 1 [ SOD 1 ], SOD2 , glutathione peroxidase [ GPx ]) were determined by quantitative real-time polymerase chain reaction. Glutathione was also measured. Results Right and left hind limb mitochondrial functions were similar in controls and after IR. IR reduced Vmax (–21.2%, 6.6 ± 1 vs 5.2 ± 1 μmol O2 /min/g dry weight, P = .001), Vsucc (–22.2%, P = .032), and VTMPD (–22.4%, P = .033), and increased Bax (63.4%, P = .020) and Bax / Bcl-2 ratio (+84.6%, P = .029). SODs and GPx messenger RNA were not modified, but glutathione tended to be decreased after IR. Local IPC and rIPC counteracted similarly these deleterious effects, restoring mitochondrial maximal oxidative capacities and normalizing Bax , the Bax / Bcl-2 ratio, and glutathione. Conclusions Remote ischemic preconditioning protection against IR injury is equivalent to that achieved by local IPC. It might deserve a broader use in clinical practice.