Ischemic preconditioning upregulates Mitofusin2 and preserves muscle strength in tourniquet-induced ischemia/reperfusion.
J Orthop Translat
; 35: 113-121, 2022 Jul.
Article
in En
| MEDLINE
| ID: mdl-36312592
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 âmin after tourniquet (TQ) inflation and the onset of reperfusion. Western blot analysis was performed in muscle protein for 4-HNE, SOD2, TNF-É, IL-6, p-Drp1ser616, Drp1, Mfn1, Mfn2, Opa1, PGC-1É, ETC complex I-V, cytochrome c, cleaved caspase-3, and caspase-3. Clinical outcomes including isokinetic muscle strength and quality of life were evaluated pre- and postoperatively. Results: IPC significantly increased Mfn2 (2.0 â± â0.2 vs 1.2 â± â0.1, p â= â0.001) and Opa1 (2.9 â± â0.3 vs 1.9 â± â0.2, p â= â0.005) proteins expression at the onset of reperfusion, compared to the ischemic phase. There were no differences in 4-HNE, SOD2, TNF-É, IL-6, p-Drp1ser616/Drp1, Mfn1, PGC-1É, ETC complex I-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 â= â0.020), while that in the IPC group was preserved (-4.7 [-25.3, 16.0] N.m, p â= â0.617). 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 preventing skeletal muscle I/R injury. IPC applied before TQ-induced I/R preserved postoperative quadriceps muscle strength after TKA.
4-HNE, 4-hydroxy-2-nonenal; ADP, Adenosine diphosphate; ASA, American Society of Anesthesiologists; ATP, Adenosine triphosphate; BSA, Bovine serum albumin; CAT, Catalase; CHOP, C/EBP homologous protein; Drp1, Dynamin-related protein-1; ER, Endoplasmic reticulum; ETC, Electron transport chain; FGF21, Fibroblast growth factor 21; Fis1, Fission protein-1; GPx, Glutathione peroxidase; I/R, Ischemia and reperfusion; IL-6, Interleukin-6; IPACK, Interspace between the popliteal artery and capsule of the posterior knee; IPC, Ischemic preconditioning; Ischemia reperfusion injury; Ischemic preconditioning; Knee arthroplasty; MDA, Malondialdehyde; Mfn, Mitofusin; Mitochondrial dynamics; MnSOD, Manganese superoxide dismutase; NF-κB, Nuclear factor kappa B; OXPHOS, Oxidative phosphorylation; PGC-1É, Peroxisome proliferator-activated receptor-gamma coactivator-1É; RIPC, Remote ischemic preconditioning; ROS, Reactive oxygen species; SBP, Systolic blood pressure; SOD, Superoxide dismutase; TKA, Total knee arthroplasty; TNF, Tumor necrosis factor; TQ, Tourniquet; Tourniquet; UPR, Unfolded protein response; mPTP, Mitochondrial permeability transition pore
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Type of study:
Clinical_trials
Aspects:
Patient_preference
Language:
En
Journal:
J Orthop Translat
Year:
2022
Document type:
Article
Affiliation country:
Tailandia
Country of publication:
Singapur