Molecular Indicators of Isometric Exercises Efficacy in Early Rehabilitation of Older Adults after Total Hip Arthroplasty

Developing molecular methods for assessing the effectiveness of physical rehabilitation remains a pressing task. Our study aimed to assess the utility of transcriptome analysis of muscle biopsies in evaluating the efficacy of the isometric exercises (IE) added to the standard protocol in early rehabilitation of older patients during the initial two weeks post total hip arthroplasty (THA). Blood concentrations of total leukocytes, neutrophils, IL6, IL8, IL1ß, myoglobin, etc. were measured, and transcriptome analysis of rectus femoris biopsies from the operated leg was performed before and after (1 and 12 days) THA in women aged 73–77 years. The additional IE in the experimental rehabilitation group led to a significant acceleration in the recovery of IL6, IL8 and IL1ß blood levels to the normal ranges compared to the control group, as confirmed by Fisher's exact test for this cytokine combination. The results of Gene Set Enrichment Analysis and Differen-tially Expressed Gene Analyses for the muscle biopsies point to accelerated resolution of inflammation, along with enhanced activation of genes associated with angiogenesis, lymphangiogenesis, vasodilation, and vasoconstriction in the experimental rehabilita-tion group compared to the control group. Thus, IL6, IL8 and IL1ß blood levels can serve being in combination as molecular indicators of the efficacy of early rehabilitation after THA, and transcriptome analysis of the rectus femoris biopsies of the operated leg allows revealing molecular indicators of regenerative processes in muscle tissue near the surgery area after THA. Overall design: Eight female patients aged 73–77 years underwent THA. Exclusion criteria included the presence of acute or decompensated somatic conditions, as well as those with any severe comorbidities that, in the physician's judgement, could hinder study participation, were excluded. Patient exclusion criteria due to failure to comply with protocol requirements were anticipated but not implemented, and all patients fully completed the rehabilitation programs. Patients were allocated to two groups sequentially (without formal randomization) as they were enrolled according to the dates of their hospitalization. Control group (n=4) followed standard IE protocols in accordance with the Russian Ministry of Health's national clinical guidelines “Coxarthrosis”. Patients of the experimental group (n=4) performed a novel rehabilitation regimen incorporating additional IE, as described in our patent. Rehabilitation was initiated on the first postoperative day following THA and continued for 12 consecutive days. Each patient underwent two daily sessions, with session duration ranging from 15 minutes to 1 hour depending on the assigned rehabilitation protocol. The clinical parameters of blood, ESR, CRP, and the concentrations of some pro-inflammatory interleukins (IL6, IL8, IL1ß) in the blood were evaluated before the THR, as well as 1 day and 12 days after the THR for each patient. At these times, rectus femoris biopsies of the operated leg were performed from each patient for transcriptomic analysis.