Theory-based and evidence-based nursing interventions for the prevention of ICU-acquired weakness in the intensive care unit: A systematic review.

OBJECTIVES: To synthesise and map the evidence of a theory- and evidence-based nursing intervention for the prevention of ICU-acquired weakness and evaluate its effectiveness in terms of the incidence of ICU-acquired weakness, incidence of delirium, and length of hospital stay. METHODS: We searched PubMed, CINAHL, MEDLINE, Academic Search Complete, Embase, Scopus, Web of Science and the Cochrane Library from database inception to November 2023. The eligible studies focused on critically ill patients in the intensive care unit, used a theory- and evidence-based nursing intervention, and reported the incidence of ICU-acquired weakness and/or used the Medical Research Council Scale. The methodological quality of the included studies was critically appraised by two authors using the appropriate Joanna Briggs Institute appraisal tool for randomised controlled trials, quasi-experimental studies, and cohort studies. Additionally, the weighted kappa coefficient was used to assess inter-rater agreement of the quality assessment. Data were reported using a narrative synthesis. This systematic review was registered by the International Prospective Register of Systematic Review (PROSPERO; CRD42023477011). RESULTS: A total of 5162 studies were initially retrieved, and 9 studies were eventually included after screening. This systematic review revealed that preventive nursing interventions for ICU-acquired weakness mainly include (a) physiotherapy, including neuromuscular electrical stimulation and early rehabilitation, and (b) nutritional support. In addition, (c) airway management, (d) sedation and analgesia management, (e) complication prevention (delirium, stress injury and deep vein thrombosis prevention), and (f) psychological care were also provided. The theories are dominated by goal-oriented theories, and the evidence is mainly the ABCDE bundle in the included studies. The results show that theory- or evidence-based nursing interventions are effective in reducing the incidence of ICU-acquired weakness (or improving the Medical Research Council Scale scores), decreasing the incidence of delirium, shortening the length of hospital stay, and improving patients' self-care and quality of life. CONCLUSION: Theory- and evidence-based nursing interventions have good results in preventing ICU-acquired weakness in critically ill patients. Current nursing interventions favour a combination of multiple interventions rather than just a single intervention. Therefore, preventive measures for ICU-acquired weakness should be viewed as complex interventions and should be based on theory or evidence. This systematic review is based on a small number of trials. Thus, more high-quality randomised controlled trials are needed to draw definitive conclusions about the impact of theory- and evidence-based nursing interventions on the prevention of ICU-acquired weakness.

Effectiveness of physical exercise and neuromuscular electrical stimulation interventions for preventing and treating intensive care unit-acquired weakness: A systematic review of randomized controlled trials.

OBJECTIVE: Intensive care unit-acquired weakness is a frequent problem that develops as a secondary disorder while patients are suffering from life-threatening conditions. This study aimed to evaluate the effectiveness of physical exercise or neuromuscular electrical stimulation interventions on (i) preventing loss of muscle mass and weakness in critically ill patients admitted to intensive care units; (ii) recovering patients discharged from the intensive care unit with acquired weakness. METHODS: A systematic review of randomized controlled trials was carried out, with studies identified in PubMed, Scopus, and Web of Science. The studies included assessed muscle mass and muscle strength, and performed a time × group analysis of effects. The risk of bias assessment was performed using the Revised Cochrane risk-of-bias tool for randomized trials. RESULTS: Six trials with low risk of bias examined muscle mass, muscle strength, and functionality in 182 adult patients. In critically ill patients admitted to intensive care units, both neuromuscular electrical stimulation and bed/chair cycling for five to ten days prevented significant muscle loss. neuromuscular electrical stimulation in lower and upper limbs resulted in a significant reduction in the length of the hospitalization. In addition, cycle ergometer increased muscle strength and functionality. In patients discharged from the intensive care unit with acquired weakness, both neuromuscular electrical stimulation and physical exercise interventions increased muscle strength, but only physical exercise increased functionality. CONCLUSIONS: Physical exercise and neuromuscular electrical stimulation interventions prevent excessive muscle mass loss in critically ill patients admitted to the intensive care unit and increase muscle strength in patients discharged from the intensive care unit with acquired weakness. Physical exercise seems more adequate for improving functionality.

Influence of Early Multidisciplinary Collaboration on Prevention of ICU-Acquired Weakness in Critically Ill Patients.

Objective: This study focused on elucidating the influence of early multidisciplinary collaboration on preventing intensive care unit- (ICU-) acquired weakness (AW) in critically ill patients (CIPs). Methods: Ninety-five CIPs admitted between December 2018 and December 2021 were selected and assigned to the following two groups according to the intervention pattern: the control group (the Con; n = 40) treated with routine early rehabilitation intervention, and the research group (the Res; n = 55) intervened by early multidisciplinary collaborative intervention. The incidence of complications (ICU-AW, deep vein thrombosis (DVT), and pressure ulcers (PSs)) and recovery indices (days of ventilator use, ICU treatment time, and length of hospital stay (LOS)) were recorded. Besides, patients' activity function and quality of life (QoL) were evaluated and compared, among which the former was evaluated by the Barthel Index (BI), ICU Mobility Scale (IMS), and Medical Research Council (MRC) Scale, and the latter was assessed by the World Health Organization Quality of Life Assessment (100-item version) (WHOQOL-100). Results: The data identified statistically a lower incidence of complications (ICU-AW, DVT, and PSs) and shorter time of ventilator use, ICU residence, and LOS in the Res compared with the Con. In addition, BI, IMS, MRC, and WHOQOL-100 scores in the Res elevated statistically after treatment and were higher than those of the Con. Conclusions: Early multidisciplinary collaboration can validly prevent ICU-AW in CIPs, reduce the incidence of DVT and PSs, and promote patients' rehabilitation, mobility, and QoL.

A Global Survey on Diagnostic, Therapeutic and Preventive Strategies in Intensive Care Unit-Acquired Weakness.

Background and Objectives: Intensive care unit-acquired weakness (ICU-AW) is one of the most frequent neuromuscular complications in critically ill patients. We conducted a global survey to evaluate the current practices of diagnostics, treatment and prevention in patients with ICU-AW. Materials and Methods: A pre-survey was created with international experts. After revision, the final survey was endorsed by the European Society of Intensive Care Medicine (ESICM) using the online platform SurveyMonkey®. In 27 items, we addressed strategies of diagnostics, therapy and prevention. An invitation link was sent by email to all ESICM members. Furthermore, the survey was available on the ESICM homepage. Results: A total of 154 healthcare professionals from 39 countries participated in the survey. An ICU-AW screening protocol was used by 20% (28/140) of participants. Forty-four percent (62/141) of all participants reported performing routine screening for ICU-AW, using clinical examination as the method of choice (124/141, 87.9%). Almost 63% (84/134) of the participants reported using current treatment strategies for patients with ICU-AW. The use of treatment and prevention strategies differed between intensivists and non-intensivists regarding the reduction in sedatives (80.0% vs. 52.6%, p = 0.002), neuromuscular blocking agents (76.4% vs. 50%, p = 0.004), corticosteroids (69.1% vs. 37.2%, p < 0.001) and glycemic control regimes (50.9% vs. 23.1%, p = 0.002). Mobilization and physical activity are the most frequently reported treatment strategies for ICU-AW (111/134, 82.9%). The availability of physiotherapists (92/134, 68.7%) and the lack of knowledge about ICU-AW within the medical team (83/134, 61.9%) were the main obstacles to the implementation of the strategies. The necessity to develop guidelines for the screening, diagnosing, treatment and prevention of ICU-AW was recognized by 95% (127/133) of participants. Conclusions: A great heterogeneity regarding diagnostics, treatment and prevention of ICU-AW was reported internationally. Comprehensive guidelines with evidence-based recommendations for ICU-AW management are needed.

Efficacy and safety of ketone ester infusion to prevent muscle weakness in a mouse model of sepsis-induced critical illness.

In septic mice, 3-hydroxybutyrate-sodium-salt has shown to partially prevent sepsis-induced muscle weakness. Although effective, the excessive sodium load was toxic. We here investigated whether ketone ester 3-hydroxybutyl-3-hydroxybutanoate (3HHB) was a safer alternative. In a mouse model of abdominal sepsis, the effects of increasing bolus doses of 3HHB enantiomers on mortality, morbidity and muscle force were investigated (n = 376). Next, plasma 3HB- clearance after bolus D-3HHB was investigated (n = 27). Subsequently, in septic mice, the effect on mortality and muscle force of a continuous D,L-3HHB infusion was investigated (n = 72). In septic mice, as compared with placebo, muscle force was increased at 20 mmol/kg/day L-3HHB and at 40 mmol/kg/day D- and D,L-3HHB. However, severity of illness and mortality was increased by doubling the effective bolus doses. Bolus 3HHB caused a higher 3HB- plasma peak and slower clearance with sepsis. Unlike bolus injections, continuous infusion of D,L-3HHB did not increase severity of illness or mortality, while remaining effective in improving muscle force. Treatment of septic mice with the ketone ester 3HHB partly prevented muscle weakness. Toxicity of 3HHB administered as bolus was completely avoided by continuous infusion of the same dose. Whether continuous infusion of ketone esters represents a promising intervention to also prevent ICU-acquired weakness in human patients should be investigated.

Balanced modulation of neuromuscular synaptic transmission via M1 and M2 muscarinic receptors during inhibition of cholinesterases.

Organophosphorus (OP) compounds that inhibit acetylcholinesterase are a common cause of poisoning worldwide, resulting in several hundred thousand deaths each year. The pathways activated during OP compound poisoning via overstimulation of muscarinic acetylcholine receptors (mAChRs) play a decisive role in toxidrome. The antidotal therapy includes atropine, which is a nonspecific blocker of all mAChR subtypes. Atropine is efficient for mitigating depression in respiratory control centers but does not benefit patients with OP-induced skeletal muscle weakness. By using an ex vivo model of OP-induced muscle weakness, we studied the effects of the M1/M4 mAChR antagonist pirenzepine and the M2/M4 mAChR antagonist methoctramine on the force of mouse diaphragm muscle contraction. It was shown that weakness caused by the application of paraoxon can be significantly prevented by methoctramine (1 µM). However, neither pirenzepine (0.1 µM) nor atropine (1 µM) was able to prevent muscle weakness. Moreover, the application of pirenzepine significantly reduced the positive effect of methoctramine. Thus, balanced modulation of neuromuscular synaptic transmission via M1 and M2 mAChRs contributes to paraoxon-induced muscle weakness. It was shown that methoctramine (10 µmol/kg, i.p.) and atropine (50 µmol/kg, i.p.) were equieffective toward increasing the survival of mice poisoned with a 2xLD50 dose of paraoxon.

Effects of ß-hydroxy-ß-methylbutyrate supplementation on muscle mass and strength in onabotulinumtoxin type-A-injected and contralateral quadriceps femoris in rabbits.

OBJECTIVE: To determine the effects of the leucine metabolite ß-hydroxy-ß-methylbutyrate (HMB) on strength, muscle mass, and contractile material in muscle wasting induced by onabotulinumtoxin type-A (BoNT-A) injection into the quadriceps femoris muscles of New Zealand white rabbits. METHODS: A total of 21, female rabbits were divided into 3 groups (n=7, each). Group 1 (Control) received intramuscular injection of saline. Groups 2 and 3 received intramuscular injection of BoNT-A (3.5 units/kg), with group 3 receiving supplementation with HMB (120 mg/kg-BW/day). Muscle morphology, mass, and strength were assessed 8 weeks later in both injected and non-injected contralateral limbs. RESULTS: Injected muscle strength of group 2 (BoNT-A) and group 3 (BoNT-A+HMB) was reduced by 63% and 60%, respectively, compared with Controls (p<0.0001). Strength in contralateral muscles of group 2 was reduced by 23% vs Controls (p<0.002), while in group 3, strength was similar to Controls. Muscle mass in the injected muscles of the BoNT-A and BoNT-A+HMB groups was significantly reduced, by 46% and 48%, respectively. CONCLUSION: While HMB did not prevent loss of muscle strength and mass in the BoNT-A-injected musculature, it prevented significant loss of contractile material in the injected musculature and strength loss in the contralateral non-injected musculature.

Angiotensin 1-7 protects against ventilator-induced diaphragm dysfunction.

Mechanical ventilation (MV) is a life-saving instrument used to provide ventilatory support for critically ill patients and patients undergoing surgery. Unfortunately, an unintended consequence of prolonged MV is the development of inspiratory weakness due to both diaphragmatic atrophy and contractile dysfunction; this syndrome is labeled ventilator-induced diaphragm dysfunction (VIDD). VIDD is clinically important because diaphragmatic weakness is an important contributor to problems in weaning patients from MV. Investigations into the pathogenesis of VIDD reveal that oxidative stress is essential for the rapid development of VIDD as redox disturbances in diaphragm fibers promote accelerated proteolysis. Currently, no standard treatment exists to prevent VIDD and, therefore, developing a strategy to avert VIDD is vital. Guided by evidence indicating that activation of the classical axis of the renin-angiotensin system (RAS) in diaphragm fibers promotes oxidative stress and VIDD, we hypothesized that activation of the nonclassical RAS signaling pathway via angiotensin 1-7 (Ang1-7) will protect against VIDD. Using an established animal model of prolonged MV, our results disclose that infusion of Ang1-7 protects the diaphragm against MV-induced contractile dysfunction and fiber atrophy in both fast and slow muscle fibers. Further, Ang1-7 shielded diaphragm fibers against MV-induced mitochondrial damage, oxidative stress, and protease activation. Collectively, these results reveal that treatment with Ang1-7 protects against VIDD, in part, due to diminishing oxidative stress and protease activation. These important findings provide robust evidence that Ang1-7 has the therapeutic potential to protect against VIDD by preventing MV-induced contractile dysfunction and atrophy of both slow and fast muscle fibers.

Prolonging the duration of cooling does not enhance recovery following a marathon.

Runners commonly utilize cryotherapy as part of their recovery strategy. Cryotherapy has been ineffective in mitigating signs and symptoms of muscle damage following marathon running and is limited by its duration of application. Phase change material (PCM) packs can prolong the duration of cooling. This study aimed to test the efficacy of prolonging the duration of cooling using PCM on perceptual recovery, neuromuscular function, and blood markers following a marathon run. Thirty participants completed a marathon run and were randomized to receive three hours of 15°C PCM treatment covering the quadriceps or recover without an intervention (control). Quadriceps soreness, strength, countermovement jump (CMJ) height, creatine kinase (CK), and high sensitivity C-reactive protein (hsCRP) were recorded at baseline, 24, 48, and 72 hours after the marathon. Following the marathon, strength decreased in both groups (P < .0001), with no difference between groups. Compared to baseline, strength was reduced 24 (P = .004) and 48 hours after the marathon (P = .008) in the control group, but only 24 hours (P = .028) in the PCM group. Soreness increased (P < .0001) and CMJ height decreased (P < .0001) in both groups, with no difference between groups. Compared to baseline, CMJ height was not reduced on any days in the PCM group but was reduced in the control group 24 (P < .0001) and 48 hours (P = .003) after the marathon. CK and hsCRP increased in both groups (P < .0001). Although the marathon run induced significant muscle damage, prolonging the duration of cooling using PCM did not accelerate the resolution of any dependent variables.

Characteristics of effective home-based resistance training in patients with noncommunicable chronic diseases: a systematic scoping review of randomised controlled trials.

Skeletal muscle atrophy, dysfunction, and weakness are consequences of noncommunicable diseases which result in exercise and functional limitations which contribute to poor quality of life and increased mortality. Home-based resistance training may promote skeletal muscle health. Electronic-based systematic searches were performed identifying randomised controlled trials utilising home-based resistance training in patients with noncommunicable diseases defined as cancer, cardiovascular disease, diabetes mellitus (type 1 and 2), chronic kidney disease (including dialysis), and chronic respiratory disease (asthma, chronic obstructive pulmonary disease, pulmonary hypertension). A comparator group was defined as one containing "non-exercise" or "usual care". Of the 239 studies identified (published between 1996 and 2020), 22 met the inclusion criteria. Sixteen studies contained an adjunct aerobic training component. Study designs and outcome measures showed large variation. Reporting of the principles of training applied within interventions was poor. Heterogeneity in study characteristics, and poor reporting of training characteristics, prevents formal recommendations for optimising home-based resistance training. However, home-based interventions are less resource-intensive than supervised programmes and appear to have the ability to improve or preserve pertinent outcomes such as strength, functional ability, and quality of life; potentially reducing the risk of mortality in patients with chronic disease.

Intraoperative Lumbar Muscle Motor Evoked Potential Monitoring With Transcortical Stimulation.

BACKGROUND: Stimulating electrodes for lower extremity motor-evoked potential (LE-MEP) monitoring with transcortical stimulation are usually placed on the medial side of motor cortex convexity, which is not lower extremity but lumbar motor area. Lumbar MEP may be elicited with lower stimulation intensity than LE-MEP through this location, and it is useful to monitor lower extremity motor function intraoperatively. METHODS: Intraoperative lumbar and LE-MEP monitoring with transcortical stimulation during surgery of 12 patients with lesions involving the motor cortex from January 2012 to February 2019 at Shinshu University Hospital were reviewed retrospectively. Stimulations were delivered by a train of 5 pulses of anodal constant current stimulation. Stimulating electrode position was determined by motor cortex mapping. Recording needle electrodes were placed on bilateral lumbar muscles and contralateral leg muscles. The threshold-level stimulation method was used for MEP monitoring. The thresholds, monitoring result, and postoperative motor function of lumbar and lower extremities were compared. RESULTS: The mean baseline thresholds were 19.9 ± 8.9 mA for lumbar MEP and 26.5 ± 11.5 mA for LE-MEP (P = 0.02). Patterns of intraoperative monitoring changes were the same between lumbar and LE-MEP monitoring. CONCLUSIONS: Lumbar MEP was stimulated with lower stimulation intensity than the LE-MEP with the same intraoperative pattern of waveform changes in 12 patients. Lumbar MEP monitoring may be useful for preserving the corticospinal tract of lower extremities intraoperatively.

Restoration of Sarcoplasmic Reticulum Ca2+ ATPase (SERCA) Activity Prevents Age-Related Muscle Atrophy and Weakness in Mice.

Sarcopenia has a significant negative impact on healthspan in the elderly and effective pharmacologic interventions remain elusive. We have previously demonstrated that sarcopenia is associated with reduced activity of the sarcoplasmic reticulum Ca2+ ATPase (SERCA) pump. We asked whether restoring SERCA activity using pharmacologic activation in aging mice could mitigate the sarcopenia phenotype. We treated 16-month male C57BL/6J mice with vehicle or CDN1163, an allosteric SERCA activator, for 10 months. At 26 months, maximal SERCA activity was reduced 41% in gastrocnemius muscle in vehicle-treated mice but maintained in old CDN1163 treated mice. Reductions in gastrocnemius mass (9%) and in vitro specific force generation in extensor digitorum longus muscle (11%) in 26 versus 16-month-old wild-type mice were also reversed by CDN1163. CDN1163 administered by intra-peritoneal injection also prevented the increase in mitochondrial ROS production in gastrocnemius muscles of aged mice. Transcriptomic analysis revealed that these effects are at least in part mediated by enhanced cellular energetics by activation of PGC1-α, UCP1, HSF1, and APMK and increased regenerative capacity by suppression of MEF2C and p38 MAPK signaling. Together, these exciting findings are the first to support that pharmacological targeting of SERCA can be an effective therapy to counter age-related muscle dysfunction.

Intensive Care Unit-Acquired Weakness: Not just Another Muscle Atrophying Condition.

Intensive care unit-acquired weakness (ICUAW) occurs in critically ill patients stemming from the critical illness itself, and results in sustained disability long after the ICU stay. Weakness can be attributed to muscle wasting, impaired contractility, neuropathy, and major pathways associated with muscle protein degradation such as the ubiquitin proteasome system and dysregulated autophagy. Furthermore, it is characterized by the preferential loss of myosin, a distinct feature of the condition. While many risk factors for ICUAW have been identified, effective interventions to offset these changes remain elusive. In addition, our understanding of the mechanisms underlying the long-term, sustained weakness observed in a subset of patients after discharge is minimal. Herein, we discuss the various proposed pathways involved in the pathophysiology of ICUAW, with a focus on the mechanisms underpinning skeletal muscle wasting and impaired contractility, and the animal models used to study them. Furthermore, we will explore the contributions of inflammation, steroid use, and paralysis to the development of ICUAW and how it pertains to those with the corona virus disease of 2019 (COVID-19). We then elaborate on interventions tested as a means to offset these decrements in muscle function that occur as a result of critical illness, and we propose new strategies to explore the molecular mechanisms of ICUAW, including serum-related biomarkers and 3D human skeletal muscle culture models.

Intensive care unit acquired weakness: A protocol for an overview of systematic reviews and meta-analysis.

BACKGROUND: Intensive care unit-acquired weakness (ICU-AW) is an acquired neuromuscular lesion and a common occurrence in patients who are critically ill. There are already systematic reviews on ICU-AW. Therefore, we provide a protocol for an overview of systematic reviews to improve the effectiveness of the construction of an evidence-based practice for prevention of ICU-AW. METHODS: We will search the PubMed, CINAHL, EMBASE, and the Cochrane Library for the relevant systematic review or meta-analyses about ICU-AW. Study selection, data extraction, and the quality assessment of the included studies will be performed independently by 2 reviewers. And the methodological quality, report quality and evidence quality will be evaluated by Assessment of Multiple Systematic Reviews-2 tool, Preferred Reporting Items for Systematic Reviews and Meta Analyses Statement checklist and Grading of Recommendations Assessment, Development and Evaluation system, respectively. RESULTS: This overview of systematic reviews and meta-analysis will collect the evidence published about the ICU-AW. CONCLUSION: We hope that our research will contribute to clinicians and public decision making about the ICU-AW. REGISTRATION NUMBER: INPLASY202070067.

Effect of early activity combined with early nutrition on acquired weakness in ICU patients.

INTRODUCTION: Intensive care unit-acquired weakness (ICU-AW) occurs in 25% to 100% of critically ill patients, and is associated with prolonged mechanical ventilation, extended ICU stay, and total hospital stay, increased hospital costs, higher risk of death, impaired physical function, and decreased quality of life. However, there are not any current guidelines that mention management of ICU-AW. The present study will evaluate the effects of a combination of early nutrition and early exercise compared to those of either early exercise alone or the standard care for patients in ICUs. METHODS: This is a 3-arm, parallel, randomized controlled trial including an estimated 147 critically ill patients aged ≥18 years recruited from the ICUs of 2 hospitals in Heilongjiang, China. Patients will be prospectively randomized 1:1:1 to receive early mobilization, early nutrition combined with early mobilization, or standard care (minimal exercises, experience-based initiation and enrollment of nutrition support). Outcomes are assessed at ICU discharge after baseline. The primary outcome is occurrence of ICU-AW according to the Medical Research Council scale at the end of treatment. Muscle strength, organ failure, functional independence, self-care ability, time of ICU stay, duration of mechanical ventilation, and ICU mortality are secondary outcome measures. DISCUSSION: This trial has the potential to identify a novel strategy for preventing or managing ICU-AW. The findings may increase the clinical knowledge about nutrition and mobilization interventions for people with ICU-AW, and contribute to the formation of practice guidelines for managing this condition. TRIAL REGISTRATION NUMBER: ChiCTR2000033482.

The Use of Recombinant Human Growth Hormone to Protect Against Muscle Weakness in Patients Undergoing Anterior Cruciate Ligament Reconstruction: A Pilot, Randomized Placebo-Controlled Trial.

BACKGROUND: Anterior cruciate ligament (ACL) tears are common knee injuries. Despite undergoing extensive rehabilitation after ACL reconstruction (ACLR), many patients have persistent quadriceps muscle weakness that limits their successful return to play and are also at an increased risk of developing knee osteoarthritis (OA). Human growth hormone (HGH) has been shown to prevent muscle atrophy and weakness in various models of disuse and disease but has not been evaluated in patients undergoing ACLR. HYPOTHESIS: Compared with placebo treatment, a 6-week perioperative treatment course of HGH would protect against muscle atrophy and weakness in patients undergoing ACLR. STUDY DESIGN: Randomized controlled trial; Level of evidence, 2. METHODS: A total of 19 male patients (aged 18-35 years) scheduled to undergo ACLR were randomly assigned to the placebo (n = 9) or HGH (n = 10) group. Patients began placebo or HGH treatment twice daily 1 week before surgery and continued through 5 weeks after surgery. Knee muscle strength and volume, patient-reported outcome scores, and circulating biomarkers were measured at several time points through 6 months after surgery. Mixed-effects models were used to evaluate differences between treatment groups and time points, and as this was a pilot study, significance was set at P < .10. The Cohen d was calculated to determine the effect size. RESULTS: HGH was well-tolerated, and no differences in adverse events between the groups were observed. The HGH group had a 2.1-fold increase in circulating insulin-like growth factor 1 over the course of the treatment period (P < .05; d = 2.93). The primary outcome measure was knee extension strength, and HGH treatment increased normalized peak isokinetic knee extension torque by 29% compared with the placebo group (P = .05; d = 0.80). Matrix metalloproteinase-3 (MMP3), which was used as an indirect biomarker of cartilage degradation, was 36% lower in the HGH group (P = .05; d = -1.34). HGH did not appear to be associated with changes in muscle volume or patient-reported outcome scores. CONCLUSION: HGH improved quadriceps strength and reduced MMP3 levels in patients undergoing ACLR. On the basis of this pilot study, further trials to more comprehensively evaluate the ability of HGH to improve muscle function and potentially protect against OA in patients undergoing ACLR are warranted. REGISTRATION: NCT02420353 ( ClinicalTrials.gov identifier).

MitoTEMPOL, a mitochondrial targeted antioxidant, prevents sepsis-induced diaphragm dysfunction.

Clinical studies indicate that sepsis-induced diaphragm dysfunction is a major contributor to respiratory failure in mechanically ventilated patients. Currently there is no drug to treat this form of diaphragm weakness. Sepsis-induced muscle dysfunction is thought to be triggered by excessive mitochondrial free radical generation; we therefore hypothesized that therapies that target mitochondrial free radical production may prevent sepsis-induced diaphragm weakness. The present study determined whether MitoTEMPOL, a mitochondrially targeted free radical scavenger, could reduce sepsis-induced diaphragm dysfunction. Using an animal model of sepsis, we compared four groups of mice: 1) sham-operated controls, 2) animals with sepsis induced by cecal ligation puncture (CLP), 3) sham controls given MitoTEMPOL (10 mg·kg-1·day-1 ip), and 4) CLP animals given MitoTEMPOL. At 48 h after surgery, we measured diaphragm force generation, mitochondrial function, proteolytic enzyme activities, and myosin heavy chain (MHC) content. We also examined the effects of delayed administration of MitoTEMPOL (by 6 h) on CLP-induced diaphragm weakness. The effects of MitoTEMPOL on cytokine-mediated alterations on muscle cell superoxide generation and cell size in vitro were also assessed. Sepsis markedly reduced diaphragm force generation. Both immediate and delayed MitoTEMPOL administration prevented sepsis-induced diaphragm weakness. MitoTEMPOL reversed sepsis-mediated reductions in mitochondrial function, activation of proteolytic pathways, and decreases in MHC content. Cytokines increased muscle cell superoxide generation and decreased cell size, effects that were ablated by MitoTEMPOL. MitoTEMPOL and other compounds that target mitochondrial free radical generation may be useful therapies for sepsis-induced diaphragm weakness.

Effects of 21 days of bed rest and whey protein supplementation on plantar flexor muscle fatigue resistance during repeated shortening contractions.

PURPOSE: Space flight and bed rest (BR) lead to a rapid decline in exercise capacity. Whey protein plus potassium bicarbonate diet-supplementation (NUTR) could attenuate this effect by improving oxidative metabolism. We evaluated the impact of 21-day BR and NUTR on fatigue resistance of plantar flexor muscles (PF) during repeated shortening contractions, and whether any change was related to altered energy metabolism and muscle oxygenation. METHODS: Ten healthy men received a standardized isocaloric diet with (n = 5) or without (n = 5) NUTR. Eight bouts of 24 concentric plantar flexions (30 s each bout) with 20 s rest between bouts were employed. PF muscle size was assessed by means of peripheral quantitative computed tomography. PF muscle volume was assessed with magnetic resonance imaging. PF muscle force, contraction velocity, power and surface electromyogram signals were recorded during each contraction, as well as energy metabolism (31P nuclear magnetic resonance spectroscopy) and oxygenation (near-infrared spectroscopy). Cardiopulmonary parameters were measured during an incremental cycle exercise test. RESULTS: BR caused 10-15% loss of PF volume that was partly recovered 3 days after re-ambulation, as a consequence of fluid redistribution. Unexpectedly, PF fatigue resistance was not affected by BR or NUTR. BR induced a shift in muscle metabolism toward glycolysis and some signs of impaired muscle oxygen extraction. NUTR did not attenuate the BR-induced-shift in energy metabolism. CONCLUSIONS: Twenty-one days' BR did not impair PF fatigue resistance, but the shift to glycolytic metabolism and indications of impaired oxygen extraction may be early signs of developing reduced muscle fatigue resistance.