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KNEE EXTENSOR STRENGTH, FUNCTION AND GENE EXPRESSION FOLLOWING PRE-OPERATIVE NEUROMUSCULAR ELECTRICAL STIMULATION IN TOTAL KNEE ARTHROPLASTY



Abstract

Introduction: Quadriceps femoris muscle (QFM) weakness has been associated with the development and progression of knee osteoarthritis, primarily due to arthrogenic muscle inhibition. Neuromuscular electrical stimulation (NMES) devices cause muscle contraction by circumventing these neural inhibitory feedback pathways. While it has been proposed this occurs in a reversed pattern of muscle fibre recruitment, the molecular mechanisms have not been clearly elucidated.

Methods: This randomised control efficacy study applied NMES to the affected QFM for 20 min, 5 days a week, for 8 weeks. Strength was assessed dynometrically and function determined using validated measures (timed stair climb, chair rise and 25 metre walk tests). A quantitative polymerase chain reaction (PCR) method measured quantities of types I, IIa, and IIx myosin heavy chain (MHC) mRNA of muscle specimens taken from vastus lateralis of the affected QFM. Expression of genetic markers associated with muscle wasting (MAFbx and MURF-1; E3 muscle specific ligases of the ubiquitin proteasome pathway) and muscle anabolic states (IGF-1) were also determined. Statistical analysis was performed using ANOVA’s and independent t-test’s where appropriate.

Results: Sixteen patients (10 women and 6 men) with radiologically severe knee OA were recruited and randomised into a control (n=6) or intervention (n=10) group. Groups were similar in terms of age (64.8 ± 11.0 vs. 64.6 ± 7.6; mean ± SD) and BMI (31.8 ± 6.1 vs.30.7 ± 2.9). There were significant improvements in function (stair climb [p< 0.01]; chair rise [p< 0.01]) and QFM strength (isokinetic [p< 0.01]; isometric [p< 0.01]) in the NMES group at week 8 compared to week 0. At the genetic level, IGF1 expression significantly increased two-fold in the NMES group (p< 0.05); Despite a 17% decrease in MAFbx expression, neither it nor MURF-1 changed significantly. MHC-I and MHC-IIa mRNA expression did not change in either group; MHC-IIx decreased by 42% in the NMES group only but was not statistically significant.

Conclusions: The use of an 8 week NMES program produces significant quadriceps strength gain with associated functional improvements in subjects with severe knee OA. Expression of muscle atrophy markers did not change significantly; however increased IGF-1 expression could potentially inhibit further muscle atrophy. Of the 3 MHC mRNA isoforms, only MHC-IIx demonstrated a change in response to NMES. These results would indicate NMES induces early quadriceps strength gain by a predominantly neurological adaptation.

Correspondence should be addressed to Mr Richard Wallace at Musgrave Park Hospital, 20 Stockman’s Lane, Belfast BT9 7JB, Northern Ireland.