%0 Journal Article
%T Ischemic preconditioning upregulates Mitofusin2 and preserves muscle strength in tourniquet-induced ischemia/reperfusion.
%A Leurcharusmee P
%A Sawaddiruk P
%A Punjasawadwong Y
%A Sugandhavesa N
%A Klunklin K
%A Tongprasert S
%A Sitilertpisan P
%A Apaijai N
%A Chattipakorn N
%A Chattipakorn SC
%A Leurcharusmee P
%A Sawaddiruk P
%A Punjasawadwong Y
%A Sugandhavesa N
%A Klunklin K
%A Tongprasert S
%A Sitilertpisan P
%A Apaijai N
%A Chattipakorn N
%A Chattipakorn SC
%J J Orthop Translat
%V 35
%N 0
%D Jul 2022
%M 36312592
%F 4.889
%R 10.1016/j.jot.2022.09.012
%X <B>UNASSIGNED: </B>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).<BR><B>UNASSIGNED: </B>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 tourniquet (TQ) inflation and the onset of reperfusion. Western blot analysis was performed in muscle protein for 4-HNE, SOD2, TNF-ɑ, IL-6, p-Drp1ser616, Drp1, Mfn1, Mfn2, Opa1, PGC-1ɑ, 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.<BR><B>UNASSIGNED: </B>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-ɑ, IL-6, p-Drp1ser616/Drp1, Mfn1, PGC-1ɑ, 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 ​= ​0.020), while that in the IPC group was preserved (-4.7 [-25.3, 16.0] N.m, p ​= ​0.617).<BR><B>UNASSIGNED: </B>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.<BR><B>UNASSIGNED: </B>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.