Blood flow restricted training leads to myocellular macrophage infiltration and upregulation of heat shock proteins, but no apparent muscle damage.

KEY POINTS: Muscular contractions performed using a combination of low external loads and partial restriction of limb blood flow appear to induce substantial gains in muscle strength and muscle mass. This exercise regime may initially induce muscular stress and damage; however, the effects of a period of blood flow restricted training on these parameters remain largely unknown. The present study shows that short-term, high-frequency, low-load muscle training performed with partial blood flow restriction does not induce significant muscular damage. However, signs of myocellular stress and inflammation that were observed in the early phase of training and after the training intervention, respectively, may be facilitating the previously reported gains in myogenic satellite cell content and muscle hypertrophy. The present results improve our current knowledge about the physiological effects of low-load muscular contractions performed under blood flow restriction and may provide important information of relevance for future therapeutic treatment of muscular atrophy. ABSTRACT: Previous studies indicate that low-load muscle contractions performed under local blood flow restriction (BFR) may initially induce muscle damage and stress. However, whether these factors are evoked with longitudinal BFR training remains unexplored at the myocellular level. Two distinct study protocols were conducted, covering 3 weeks (3 wk) or one week (1 wk). Subjects performed BFR exercise (100 mmHg, 20% 1RM) to concentric failure (BFRE) (3 wk/1 wk), while controls performed work-matched (LLE) (3 wk) or high-load (HLE; 70% 1RM) (1 wk) free-flow exercise. Muscle biopsies (3 wk) were obtained at baseline (Pre), 8 days into the intervention (Mid8), and 3 and 10 days after training cessation (Post3, Post10) to examine macrophage (M1/M2) content as well as heat shock protein (HSP27/70) and tenascin-C expression. Blood samples (1 wk) were collected before and after (0.1-24 h) the first and last training session to examine markers of muscle damage (creatine kinase), oxidative stress (total antibody capacity, glutathione) and inflammation (monocyte chemotactic protein-1, interleukin-6, tumour necrosis factor α). M1-macrophage content increased 108-165% with BFRE and LLE at Post3 (P < 0.05), while M2-macrophages increased (163%) with BFRE only (P < 0.01). Membrane and intracellular HSP27 expression increased 60-132% at Mid8 with BFRE (P < 0.05-0.01). No or only minor changes were observed in circulating markers of muscle damage, oxidative stress and inflammation. The amplitude, timing and localization of the above changes indicate that only limited muscle damage was evoked with BFRE. This study is the first to show that a period of high-frequency, low-load BFR training does not appear to induce general myocellular damage. However, signs of tissue inflammation and focal myocellular membrane stress and/or reorganization were observed that may be involved in the adaptation processes evoked by BFR muscle exercise.

Local anesthetic wound infiltration for pain management after periacetabular osteotomy. A randomized, placebo-controlled, double-blind clinical trial with 53 patients.

BACKGROUND AND PURPOSE: To our knowledge, there is no evidence to support the use of local infiltration analgesia (LIA) for postoperative pain relief after periacetabular osteotomy (PAO). We investigated the effect of wound infiltration with a long-acting local anesthetic (ropivacaine) for postoperative analgesia after PAO. PATIENTS AND METHODS: We performed a randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov: NCT00815503) in 53 patients undergoing PAO to evaluate the effect of local anesthetic infiltration on postoperative pain and on postoperative opioid consumption. All subjects received intraoperative infiltration followed by 5 postoperative injections in 10-hour intervals through a multi-holed catheter placed at the surgical site. 26 patients received ropivacaine and 27 received saline. The intervention period was 2 days and the observational period was 4 days. All subjects received patient-controlled opioid analgesia without any restrictions on the total daily dose. Pain was assessed at specific postoperative time points and the daily opioid usage was registered. RESULTS: Infiltration with 75 mL (150 mg) of ropivacaine did not reduce postoperative pain or opioid requirements during the first 4 days. INTERPRETATION: The clinical importance of ropivacaine as single component in postoperative treatment of pain is questionable, and we are planning further studies to explore the potential of LIA in larger volume-and also a multimodal regimen-to treat pain in this category of patients.

Stand-alone ALIF versus TLIF in patients with low back pain - A propensity-matched cohort study with two-year follow-up.

Introduction: Instrumented lumbar fusion by either the anterior or transforaminal approach has different advantages and disadvantages. Few studies have compared PatientReported Outcomes Measures (PROMs) between stand-alone anterior lumbar interbody fusion (SA-ALIF) and transforaminal lumbar interbody fusion (TLIF). Research question: This is a register-based dual-center study on patients with severe disc degeneration (DD) and low back pain (LBP) undergoing single-level SA-ALIF or TLIF. Comparing PROMs, including disability, quality of life, back- and leg-pain and patient satisfaction two years after SA-ALIF or TLIF, respectively. Material and methods: Data were collected preoperatively and at one and two-year follow-up. The primary outcome was Oswestry Disability Index (ODI). The secondary outcomes were patient satisfaction, walking ability, visual analog scale (VAS) scores for back and leg pain, and quality of life (QoL) measured by the European Quality of Life-5 Dimensions (EQ-5D) index score. To reduce baseline differences between groups, propensity-score matching was employed in a 1:1 fashion. Results: 92 patients were matched, 46 S A-ALIF and 46 TLIF. They were comparable preoperatively, with no significant difference in demographic data or PROMs (P > 0.10). Both groups obtained statistically significant improvement in the ODI, QoL and VAS-score (P < 0.01), but no significant difference was observed (P = 0.14). No statistically significant differences in EQ-5D index scores (P = 0.25), VAS score for leg pain (P = 0.88) and back pain (P = 0.37) at two years follow-up. Conclusion: Significant improvements in ODI, VAS-scores for back and leg pain, and EQ-5D index score were registered after two-year follow-up with both SA-ALIF and TLIF. No significant differences in improvement.

Skeletal Muscle Microvascular Changes in Response to Short-Term Blood Flow Restricted Training-Exercise-Induced Adaptations and Signs of Perivascular Stress.

Aim: Previous reports suggest that low-load muscle exercise performed under blood flow restriction (BFR) may lead to endurance adaptations. However, only few and conflicting results exist on the magnitude and timing of microvascular adaptations, overall indicating a lack of angiogenesis with BFR training. The present study, therefore, aimed to examine the effect of short-term high-frequency BFR training on human skeletal muscle vascularization. Methods: Participants completed 3 weeks of high-frequency (one to two daily sessions) training consisting of either BFR exercise [(BFRE) n = 10, 22.8 ± 2.3 years; 20% one-repetition maximum (1RM), 100 mmHg] performed to concentric failure or work-matched free-flow exercise [(CON) n = 8, 21.9 ± 3.0 years; 20% 1RM]. Muscle biopsies [vastus lateralis (VL)] were obtained at baseline, 8 days into the intervention, and 3 and 10 days after cessation of the intervention to examine capillary and perivascular adaptations, as well as angiogenesis-related protein signaling and gene expression. Results: Capillary per myofiber and capillary area (CA) increased 21-24 and 25-34%, respectively, in response to BFRE (P < 0.05-0.01), while capillary density (CD) remained unchanged. Overall, these adaptations led to a consistent elevation (15-16%) in the capillary-to-muscle area ratio following BFRE (P < 0.05-0.01). In addition, evaluation of perivascular properties indicated thickening of the perivascular basal membrane following BFRE. No or only minor changes were observed in CON. Conclusion: This study is the first to show that short-term high-frequency, low-load BFRE can lead to microvascular adaptations (i.e., capillary neoformation and changes in morphology), which may contribute to the endurance effects previously documented with BFR training. The observation of perivascular membrane thickening suggests that high-frequency BFRE may be associated with significant vascular stress.

Local Anesthetic Wound Infiltration after Osteosynthesis of Extracapsular Hip Fracture Does Not Reduce Pain or Opioid Requirements: A Randomized, Placebo-Controlled, Double-Blind Clinical Trial in 49 Patients.

Background and purpose: Local infiltration analgesia (LIA) supports early mobilization after hip and knee arthroplasty. Inspired by this, we studied the effectiveness of wound infiltration with the long acting local anesthetic ropivacaine in an effort to decrease the need for postoperative opioids after osteosynthesis of extracapsular hip fracture. Methods: Forty-nine patients undergoing osteosynthesis with a sliding hip screw were randomized into two groups in a double-blind study (ClinicalTrials.gov:NCT01119209). The patients received intraoperative infiltration followed by 6 postoperative injections through a wound catheter in eight-hour intervals. 23 patients received ropivacaine and 26 received saline. The intervention period was 2 days, and the observation period was 5 days. In both groups, there were no restrictions on the total daily dose of opioids. Pain was assessed at specific postoperative time points, and the daily opioid usage was registered. Results: Intraoperative infiltration with 200 mg ropivacaine and postoperative repeated infiltration with 100 mg ropivacaine did not result in statistically significant difference between the groups regarding postoperative opioid consumption or pain. Interpretation: Ropivacaine as single component in postoperative treatment of pain after hip fracture is not effective. In our setup, wound infiltration with ropivacaine is not statistically significantly better than placebo.

High Reliability of a Scoring System for Implant Position in Undisplaced Femoral Neck Fractures.

OBJECTIVES: The aim of this study was to evaluate the intrarater and interrater reliability of a scoring system for internal fixation (SIFA) in undisplaced femoral neck fractures (FNF). DESIGN: A reproducibility study with a historical consecutive cohort. SETTING: The patients were all treated at a level one trauma hospital. PATIENTS/PARTICIPANTS: A cohort of patients with FNF, treated with 2 parallel implants, was retrieved using a local county register, and the cohort was assessed for undisplaced FNF until the desired sample size was reached. One hundred two patients had their x-ray images reviewed 2 times with a minimum 14 days interval, by 3 raters, all blinded for each other's results, and an independent person analyzed the data with unweighted kappa statistics. MAIN OUTCOME MEASUREMENTS: Implant positions on the first postoperative anterior-posterior and axial radiographs were first visually assessed, then objectively measured according to SIFA, which consists of 5 individual measurements; screw tip distance, screw femoral shaft angle, inferior screw calcar distance, and screw position in the femoral head in the anterior-posterior and axial radiographs. RESULTS: Visually assessed implant position gave intrarater kappa results for the individual components of SIFA at 0.40-0.75 (rater 1), 0.75-0.98 (rater 2), and 0.69-0.83 (rater 3), with interrater kappa results at 0.18-0.80 (combined range). Objectively measured implant position for the individual components of SIFA gave intrarater kappa results at 0.56-1.0 (rater 1), 0.74-0.89 (rater 2), and 0.81-0.94 (rater 3), with interrater kappa results at 0.56-0.85 (combined range). The overall SIFA score has similar higher intrarater and interrater results for the measured (0.51-0.78) compared with the visual assessment (0.13-0.78). The assessment in the axial view of the screw position in femoral head had the largest difference of acceptable positioning, when comparing visual assessment with the measured. CONCLUSIONS: The SIFA demonstrates substantial intrarater and interrater reliability (kappa 0.51-0.78), when raters make measurements of radiographs, but lower reliability (kappa 0.13-0.78) when raters visually assess the radiographs without measuring. The SIFA should be assessed on a large cohort, for correlation with clinical evaluation.

Carbohydrate restricted recovery from long term endurance exercise does not affect gene responses involved in mitochondrial biogenesis in highly trained athletes.

The aim was to determine if the metabolic adaptations, particularly PGC-1α and downstream metabolic genes were affected by restricting CHO following an endurance exercise bout in trained endurance athletes. A second aim was to compare baseline expression level of these genes to untrained. Elite endurance athletes (VO2max 66 ± 2 mL·kg(-1)·min(-1), n = 15) completed 4 h cycling at ~56% VO2max. During the first 4 h recovery subjects were provided with either CHO or only H2O and thereafter both groups received CHO. Muscle biopsies were collected before, after, and 4 and 24 h after exercise. Also, resting biopsies were collected from untrained subjects (n = 8). Exercise decreased glycogen by 67.7 ± 4.0% (from 699 ± 26.1 to 239 ± 29.5 mmol·kg(-1)·dw(-1)) with no difference between groups. Whereas 4 h of recovery with CHO partly replenished glycogen, the H2O group remained at post exercise level; nevertheless, the gene expression was not different between groups. Glycogen and most gene expression levels returned to baseline by 24 h in both CHO and H2O. Baseline mRNA expression of NRF-1, COX-IV, GLUT4 and PPAR-α gene targets were higher in trained compared to untrained. Additionally, the proportion of type I muscle fibers positively correlated with baseline mRNA for PGC-1α, TFAM, NRF-1, COX-IV, PPAR-α, and GLUT4 for both trained and untrained. CHO restriction during recovery from glycogen depleting exercise does not improve the mRNA response of markers of mitochondrial biogenesis. Further, baseline gene expression of key metabolic pathways is higher in trained than untrained.

Local anaesthetic wound infiltration after internal fixation of femoral neck fractures: a randomized, double-blind clinical trial in 33 patients.

Pain control may assist early mobilisation after internal fixation of femoral neck fractures. Systemic opioids have significant side effects in elderly patients. We present an evaluation of the effect of local anaesthetic infiltration in such cases , the objective being to decrease the need for postoperative opioids and to improve pain control for patients after surgery. 33 patients undergoing internal fixation with 2 parallel hook pins were randomized into 2 groups in a double blind study (ClinicalTrials.gov: NCT00529425). 33 patients received intraoperative infiltration followed by 6 postoperative injections through an intraarticular catheter in eight-hour intervals. 19 patients received ropivacaine and 14 received saline. The intervention period was 48 hours and the observation period was 5 days. In both groups there were no restrictions on the total daily dose of rescue analgesics. Pain was assessed at specific postoperative time-points and the daily consumption of opioid drugs needed for analgesia was registered. There was no significantly reduced consumption of standardized opioid rescue analgesics or pain in the study group receiving ropivacaine injections. Apart from a reduction in nausea in the study group on the second postoperative day, there were no significant differences in the occurrence of side effects between the groups. On day 2 the placebo group had less pain than the study group. Local anaesthetic infiltration after fixation of femoral neck fractures does not reduce opioid consumption or pain'.