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      Protective Effects of Rocuronium Bromide on Ischemia-Reperfusion Injury in Skeletal Muscle Induced by Tourniquet in Patients Undergoing Elective Unilateral Total Knee Arthroplasty: A Prospective, Double Blind, Randomized, Controlled Study

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          To investigate the effects of different doses of rocuronium on ischemia-reperfusion injury in skeletal muscle induced by tourniquet in patients undergoing elective unilateral total knee arthroplasty.

          Patients and Methods

          A total of 90 patients undergoing elective unilateral knee arthroplasty under general anesthesia combined with femoral nerve block were randomly divided into 3 groups: normal saline group (group S), rocuronium 0.6 mg/kg group (group L), and rocuronium 1.2 mg/kg group (group H). The primary outcome was the expression of dystrophin in skeletal muscle at 60 min after ischemia. Secondary outcomes included the concentration of malondialdehyde (MDA) and neuronal nitric oxide synthase (nNOS) in blood at 5 min and 30 min after reperfusion. In addition, thigh girth at 24 h and 48 h after operation, the leaving bed time, the incidence of tourniquet-related hypertension and short-term (3 days after operation) complications (nausea and vomiting, swelling, blister, wound infection) and long-term (3 months after operation) complications (joint instability, stiffness, nerve paralysis, pain) were recorded.

          Main Results

          The expression of dystrophin in the rocuronium group was higher than that in group S after ischemia ( P <0.05). The concentration of MDA in the rocuronium 1.2 mg/kg group was lower at 30 min after reperfusion ( P < 0.05). There was no significant difference in nNOS among groups at each time point ( P > 0.05). The change of thigh girth was the smallest in the rocuronium 1.2 mg/kg group after operation ( P<0.05). The leaving bed time was significantly earlier after operation in the rocuronium group than that in group S ( P <0.05).


          Rocuronium can protect skeletal muscle from ischemia-reperfusion injury induced by tourniquet. The mechanism may be related to the fact that rocuronium can reduce the loss of dystrophin in skeletal muscle and have the effects of anti-oxidation and anti-stress.

          Trial Registration

          The study was registered at http://www.chictr.org.cn (ChiCTR1800019221, registered on 2018–10-31).

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          Most cited references 28

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          Does Tourniquet Use in TKA Affect Recovery of Lower Extremity Strength and Function? A Randomized Trial.

           Douglas A Dennis (corresponding) ,  Andrew Kittelson,  Charlie C Yang (2016)
          Tourniquet use during total knee arthroplasty (TKA) improves visibility and reduces intraoperative blood loss. However, tourniquet use may also have a negative impact on early recovery of muscle strength and lower extremity function after TKA.
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            Dystrophin-glycoprotein complex is highly enriched in isolated skeletal muscle sarcolemma

             K Ohlendieck (1991)
            mAbs specific for protein components of the surface membrane of rabbit skeletal muscle have been used as markers in the isolation and characterization of skeletal muscle sarcolemma membranes. Highly purified sarcolemma membranes from rabbit skeletal muscle were isolated from a crude surface membrane preparation by wheat germ agglutination. Immunoblot analysis of subcellular fractions from skeletal muscle revealed that dystrophin and its associated glycoproteins of 156 and 50 kD are greatly enriched in purified sarcolemma vesicles. The purified sarcolemma was also enriched in novel sarcolemma markers (SL45, SL/TS230) and Na+/K(+)-ATPase, whereas t-tubule markers (alpha 1 and alpha 2 subunits of dihydropyridine receptor, TS28) and sarcoplasmic reticulum markers (Ca2(+)-ATPase, ryanodine receptor) were greatly diminished in this preparation. Analysis of isolated sarcolemma by SDS- PAGE and densitometric scanning demonstrated that dystrophin made up 2% of the total protein in the rabbit sarcolemma preparation. Therefore, our results demonstrate that although dystrophin is a minor muscle protein it is a major constituent of the sarcolemma membrane in skeletal muscle. Thus the absence of dystrophin in Duchenne muscular dystrophy may result in a major disruption of the cytoskeletal network underlying the sarcolemma in dystrophic muscle.
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              Chronology of mitochondrial and cellular events during skeletal muscle ischemia-reperfusion.

               Stéphanie Paradis (corresponding) ,  Anne-Laure Charles,  Alain Meyer (2016)
              Peripheral artery disease (PAD) is a common circulatory disorder of the lower limb arteries that reduces functional capacity and quality of life of patients. Despite relatively effective available treatments, PAD is a serious public health issue associated with significant morbidity and mortality. Ischemia-reperfusion (I/R) cycles during PAD are responsible for insufficient oxygen supply, mitochondriopathy, free radical production, and inflammation and lead to events that contribute to myocyte death and remote organ failure. However, the chronology of mitochondrial and cellular events during the ischemic period and at the moment of reperfusion in skeletal muscle fibers has been poorly reviewed. Thus, after a review of the basal myocyte state and normal mitochondrial biology, we discuss the physiopathology of ischemia and reperfusion at the mitochondrial and cellular levels. First we describe the chronology of the deleterious biochemical and mitochondrial mechanisms activated by I/R. Then we discuss skeletal muscle I/R injury in the muscle environment, mitochondrial dynamics, and inflammation. A better understanding of the chronology of the events underlying I/R will allow us to identify key factors in the development of this pathology and point to suitable new therapies. Emerging data on mitochondrial dynamics should help identify new molecular and therapeutic targets and develop protective strategies against PAD.

                Author and article information

                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                18 August 2020
                : 14
                : 3373-3384
                [1 ]Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University , Xuzhou, Jiangsu 221004, People’s Republic of China
                Author notes
                Correspondence: Yue-Ying Zhang Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University , Huaihai Western Road, Quanshan District, Xuzhou, Jiangsu221004, People’s Republic of China Tel +86 138 1531 0789 Email zyy0218@126.com

                These authors contributed equally to this work

                © 2020 Chen et al.

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                Page count
                Figures: 4, Tables: 20, References: 29, Pages: 12
                Original Research

                Pharmacology & Pharmaceutical medicine

                tka, ischemia-reperfusion injury, dystrophin, rocuronium


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