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      Drug Design, Development and Therapy (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the design and development of drugs, as well as the clinical outcomes, patient safety, and programs targeted at the effective and safe use of medicines. Sign up for email alerts here.

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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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          Abstract

          Purpose

          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).

          Conclusion

          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).

          Most cited references28

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

          Douglas A Dennis, 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.
          Article 0 comments Cited 69 times – based on 0 reviews     Review now
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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, 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.
              Article 0 comments Cited 41 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Drug Des Devel Ther
                Journal ID (iso-abbrev): Drug Des Devel Ther
                Journal ID (publisher-id): dddt
                Journal ID (pmc): dddt
                Title: Drug Design, Development and Therapy
                Publisher: Dove
                ISSN (Electronic): 1177-8881
                Publication date (Electronic): 18 August 2020
                Publication date Collection: 2020
                Volume: 14
                Pages: 3373-3384
                Affiliations
                [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

                Author information
                http://orcid.org/0000-0003-2382-3379
                http://orcid.org/0000-0002-4103-312X
                Article
                Publisher ID: 252546
                DOI: 10.2147/DDDT.S252546
                PMC ID: 7443440
                SO-VID: 836b4780-dfbd-4ec0-9730-00b652faa6b8
                Copyright © © 2020 Chen et al.
                License:

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                Date received : 08 March 2020
                Date accepted : 26 July 2020
                Page count
                Figures: 4, Tables: 20, References: 29, Pages: 12
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: ischemia-reperfusion injury,rocuronium,dystrophin,tka
                Data availability:
                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: ischemia-reperfusion injury, rocuronium, dystrophin, tka

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