Ischemic preconditioning upregulates Mitofusin2 and preserves muscle strength in tourniquet-induced ischemia/reperfusion

Background: Tourniquet-induced ischemia and reperfusion (I/R) has been related to postoperative muscle atrophy through mechanisms involving protein synthesis/breakdown, cellular metabolism, mitochondrial dysfunction, and apoptosis. Ischemic preconditioning (IPC) could protect skeletal muscle against I/R injury. This study aims to determine the underlying mechanisms of IPC and its effect on muscle strength after total knee arthroplasty (TKA). Methods: Twenty-four TKA patients were randomized to receive either sham IPC or IPC (3 cycles of 5-min ischemia followed by 5-min reperfusion). Vastus medialis muscle biopsies were collected at 30 min after tour-niquet (TQ) inflation and the onset of reperfusion. Western blot analysis was performed in muscle protein for 4-HNE, SOD2, TNF-a, IL-6, p-Drp1ser616, Drp1, Mfn1, Mfn2, Opa1, PGC-1a, ETC complex I-V, cytochrome c, cleaved caspase-3, and caspase-3. Clinical outcomes including isokinetic muscle strength and quality of life were evalu-ated pre-and postoperatively. Results: IPC significantly increased Mfn2 (2.0 +/- 0.2 vs 1.2 +/- 0.1, p = 0.001) and Opa1 (2.9 +/- 0.3 vs 1.9 +/- 0.2, p = 0.005) proteins expression at the onset of reperfusion, compared to the ischemic phase. There were no differences in 4-HNE, SOD2, TNF-a, IL-6, p-Drp1ser616/Drp1, Mfn1, PGC-1a, ETC complex I & ndash;V, cytochrome c, and cleaved caspase-3/caspase-3 expression between the ischemic and reperfusion periods, or between the groups. Clinically, postoperative peak torque for knee extension significantly reduced in the sham IPC group (-16.6 [-29.5,-3.6] N.m, p = 0.020), while that in the IPC group was preserved (-4.7 [-25.3, 16.0] N.m, p = 0.617). Conclusion: In TKA with TQ application, IPC preserved postoperative quadriceps strength and prevented TQ-induced I/R injury partly by enhancing mitochondrial fusion proteins in the skeletal muscle. The translational potential of this article: Mitochondrial fusion is a potential underlying mechanism of IPC in pre -venting skeletal muscle I/R injury. IPC applied before TQ-induced I/R preserved postoperative quadriceps muscle strength after TKA.

Automated summary

The study found that ischemic preconditioning (IPC) can protect muscle strength after total knee arthroplasty (TKA) by enhancing mitochondrial fusion proteins and preventing I/R injury. Additionally, IPC significantly increased the expression of Mfn2 and Opa1 proteins, positively impacting postoperative muscle recovery.