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

Abstract

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 (V(max)), succinate (V(succ)), and N,N,N',N'-tetramethyl-p-phenylenediamine dihydrochloride (TMPD)-ascorbate (V(TMPD)). 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 V(max) (-21.2%, 6.6 ± 1 vs 5.2 ± 1 μmol O(2)/min/g dry weight, P = .001), V(succ) (-22.2%, P = .032), and V(TMPD) (-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.

Clinical relevance: Acute and chronic ischemia induce mitochondrial dysfunction in human skeletal muscles, and improving muscle mitochondrial function improves subjects’ status. Compared with local ischemic preconditioning (IPC), remote IPC (rIPC) appears easier to perform and is safer for the vessel and territory involved in ischemic injury. This study demonstrates that the muscle protection afforded by rIPC is equivalent to that achieved by IPC. Acknowledging that IPC procedures should be specifically adapted to patient characteristics to be successful, our results support a broader use of rIPC in the setting of vascular surgery.