Acid-base balance at high altitude in lowlanders and indigenous highlanders

High-altitude exposure results in a hyperventilatory-induced respiratory alkalosis followed by renal compensation (bicarbonaturia) to return arterial blood pH(a) toward sea-level values. However, acid-base balance has not been comprehensively examined in both lowlanders and indigenous populations - where the latter are thought to be fully adapted to high-altitude. The purpose of this investigation was to compare acid-base balance between acclimatizing lowlanders, and Andean and Sherpa highlanders at various altitudes (~3,800, ~4,300, and ~5,000 m). We compiled data collected across five independent high-altitude expeditions and report the following novel findings: 1) at 3,800 m, Andeans (n=7) had elevated pHa compared to Sherpas (n=12; P<0.01), but not to lowlanders (n=16; nine days acclimatized; P=0.09); 2) at 4,300 m, lowlanders (n=16; 21 days acclimatized) had elevated pHa compared to Andeans (n=32) and Sherpas (n=11; both P<0.01), and Andeans had elevated pHa compared to Sherpas (P=0.01); and 3) at 5,000 m, lowlanders (n=16; 14 days acclimatized) had higher pHa compared to both Andeans (n=66) and Sherpas (n=18; P<0.01, and P=0.03, respectively), and Andean and Sherpa highlanders had similar blood pHa (P=0.65). These novel data characterize acid-base balance acclimatization and adaptation to various altitudes in lowlanders and indigenous highlanders.

Modeling the Metabolic Reductions of a Passive Back-Support Exoskeleton

Despite several attempts to quantify the metabolic savings resulting from the use of passive back-support exoskeletons (BSEs), no study has modeled the metabolic change while wearing an exoskeleton during lifting. The objectives of this study were to: 1) quantify the metabolic reductions due to the VT-Lowe's exoskeleton during lifting; and 2) provide a comprehensive model to estimate the metabolic reductions from using a passive BSE. In this study, 15 healthy adults (13M, 2F) of ages 20 to 34 years (mean=25.33, SD=4.43) performed repeated freestyle lifting and lowering of an empty box and a box with 20% of their bodyweight. Oxygen consumption and metabolic expenditure data were collected. A model for metabolic expenditure was developed and fitted with the experimental data of two prior studies and the without-exoskeleton experimental results. The metabolic cost model was then modified to reflect the effect of the exoskeleton. The experimental results revealed that VT-Lowe's exoskeleton significantly lowered the oxygen consumption by ~9% for an empty box and 8% for a 20% bodyweight box, which corresponds to a net metabolic cost reduction of ~12% and ~9%, respectively. The mean metabolic difference (i.e., without-exo minus with-exo) and the 95% confidence interval were 0.36 and (0.2-0.52) [Watts/kg] for 0% bodyweight, and 0.43 and (0.18-0.69) [Watts/kg] for 20% bodyweight. Our modeling predictions for with-exoskeleton conditions were precise, with absolute freestyle prediction errors of <2.1%. The model developed in this study can be modified based on different study designs, and can assist researchers in enhancing designs of future lifting exoskeletons.

Power attenuation from restricting range of motion is minimized in subjects with fast RTD and following isometric training

Time-dependent measures consisting of rate of torque development (RTD), rate of velocity development (RVD), and rate of neuromuscular activation can be used to evaluate explosive muscular performance, which becomes critical when performing movements throughout limited ranges of motion (ROM). Using a HUMAC NORM dynamometer, seven males (27 ± 7 years) and six females (22 ± 3 years) underwent 8 weeks of maximal isometric dorsiflexion training 3 days/week. One leg was trained at 0° (short-muscle tendon unit (MTU) length) and the other at 40° of plantar flexion (long-MTU length). RTD and rate of neuromuscular activation were evaluated during 'fast' maximal isometric contractions. Power, RVD, and rate of neuromuscular activation were assessed during maximal isotonic contractions in four conditions (small (40° to 30° of plantar flexion) ROM at 10 and 50% MVC; large (40° to 0° of plantar flexion) ROM at 10 and 50% MVC) for both legs, pre- and post-training. Despite no change in rate of neuromuscular activation following training, peak power, RTD, and RVD increased at both MTU lengths (p < 0.05). Strong relationships (R2=0.73) were observed between RTD and peak power in the small ROM, indicating that fast time-dependent measures are critical for optimal performance when ROM is constrained. Meanwhile, strong relationships (R2=0.90) between RVD and power were observed at the 50% load, indicating that RVD is critical when limited by load and ROM is not confined. Maximal isometric dorsiflexion training can be used to improve time-dependent measures (RTD, RVD) to minimize power attenuation when ROM is restricted.

Methylglyoxal reduces molecular responsiveness to 4 weeks of endurance exercise in mouse plantaris muscle

Endurance exercise triggers skeletal muscle adaptations, including enhanced insulin signaling, glucose metabolism, and mitochondrial biogenesis. However, exercise-induced skeletal muscle adaptations may not occur in some cases, a condition known as exercise-resistance. Methylglyoxal (MG) is a highly reactive dicarbonyl metabolite and has detrimental effects on the body such as causing diabetic complications, mitochondrial dysfunction, and inflammation. This study aimed to clarify the effect of methylglyoxal on skeletal muscle molecular adaptations following endurance exercise. Mice were randomly divided into 4 groups (n = 12 per group): sedentary control group, voluntary exercise group, MG-treated group, and MG-treated with voluntary exercise group. Mice in the voluntary exercise group were housed in a cage with a running wheel, while mice in the MG-treated groups received drinking water containing 1% MG. Four weeks of voluntary exercise induced several molecular adaptations in the plantaris muscle, including increased expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α), mitochondria complex proteins, toll-like receptor 4 (TLR4), 72-kDa heat shock protein (HSP72), hexokinase II, and glyoxalase 1; this also enhanced insulin-stimulated Akt Ser473 phosphorylation and citrate synthase activity. However, these adaptations were suppressed with MG treatment. In the soleus muscle, the exercise-induced increases in the expression of TLR4, HSP72, and advanced glycation end products receptor 1 were inhibited with MG treatment. These findings suggest that MG is a factor that inhibits endurance exercise-induced molecular responses including mitochondrial adaptations, insulin signaling activation, and the upregulation of several proteins related to mitochondrial biogenesis, glucose handling, and glycation in primarily fast-twitch skeletal muscle.

Biometrics from a Wearable Device Reveals Temporary Effects of COVID-19 Vaccines on Cardiovascular, Respiratory, and Sleep Physiology

Although vaccines against SARS-CoV-2 have been proven safe and effective, transient side-effects lasting 24-48 hours post-vaccination have been reported. To better understand the subjective and objective response to COVID-19 vaccination, we conducted a retrospective analysis on 69619 subscribers to a wrist-worn biometric device (WHOOP Inc, Boston, MA, USA) who received either the AstraZeneca, Janssen/Johnson & Johnson, Moderna, or Pfizer/BioNTech vaccine. The WHOOP device measures resting heart rate (RHR), heart rate variability (HRV), respiratory rate (RR), and sleep architecture, and these physiological measures were normalized to the same day of the week, one week prior to vaccination. Averaging across vaccines, RHR, RR, and percent sleep derived from light sleep were elevated on the first night following vaccination and returned to baseline within four nights post-vaccination. When statistical differences were observed between doses on the first night post-vaccination, larger deviations in physiological measures were observed following the first dose of AstraZeneca and the second dose of Moderna and Pfizer/BioNTech. When statistical differences were observed between age groups or gender on the first night post-vaccination, larger deviations in physiological measures were observed in younger populations and in females (compared to males). When combining self-reported symptoms (fatigue, muscle aches, headache, chills, or fever) with the objectively measured physiological parameters, we found that self-reporting fever or chills had the strongest association with deviations in physiological measures following vaccination. In summary, these results suggest that COVID-19 vaccines temporarily affect cardiovascular, respiratory, and sleep physiology, and that dose, gender, and age affect the physiological response to vaccination.

From heart to muscle: Pathophysiological mechanisms underlying long-term physical sequelae from SARS-CoV-2 infection

The long-term sequelae of the coronavirus disease 2019 (COVID-19) are multifaceted and, besides the lungs, impact other organs and tissues, even in cases of mild infection. Along with commonly reported symptoms such as fatigue and dyspnea, a significant proportion of those with prior COVID-19 infection also exhibit signs of cardiac damage, muscle weakness, and ultimately, poor exercise tolerance. This review provides an overview of evidence indicating cardiac impairments and persistent endothelial dysfunction in the peripheral vasculature of those previously infected with COVID-19, irrespective of the severity of the acute phase of illness. Additionally, VO2peak appears to be lower in convalescent patients, which may stem, in part, from alterations in O2 transport such as impaired diffusional O2conductance. Together, the persistent multi-organ dysfunction induced by COVID-19 may set previously healthy individuals on a trajectory towards frailty and disease. Given the large proportion of individuals recovering from COVID-19, it is critically important to better understand the physical sequelae of COVID-19, the underlying biological mechanisms contributing to these outcomes, and the long-term effects on future disease risk. This review highlights relevant literature on the pathophysiology post-COVID-19 infection, gaps in the literature, and emphasizes the need for the development of evidence-based rehabilitation guidelines.

Task-dependent neural control of regions within human genioglossus

Anatomical and imaging evidence suggests neural control of oblique and horizontal compartments of the genioglossus differs. However, neurophysiological evidence for differential control remains elusive. This study aimed to determine whether there are differences in neural drive to the oblique and horizontal regions of the genioglossus during swallowing and tongue protrusion. Adult participants (N=63; 48M) were recruited from a sleep clinic; 41 had Obstructive Sleep Apnoea (OSA: 34M, 8F). Electromyographic (EMG) was recorded at rest (awake, supine) using 4 intramuscular fine-wire electrodes inserted percutaneously into the anterior oblique, posterior oblique, anterior horizontal and posterior horizontal genioglossus. Epiglottic pressure and nasal airflow were also measured. During swallowing, two distinct EMG patterns were observed- a monophasic response (single EMG peak) and a biphasic response (two bursts of EMG). Peak EMG and timing of the peak relative to epiglottic pressure were significantly different between patterns (linear mixed models, p<0.001). Monophasic activation was more likely in the horizontal than oblique region during swallowing (OR=6.83, CI=3.46-13.53, p<0.001). In contrast, during tongue protrusion, activation patterns and EMG magnitude were not different between regions. There were no systematic differences in EMG patterns during swallowing or tongue protrusion between OSA and non-OSA groups. These findings provide evidence for functional differences in the motoneuronal output to the oblique and horizontal compartments, enabling differential task-specific drive. Given this, it is important to identify the compartment from which EMG is acquired. We propose that the EMG patterns during swallowing may be used to identify the compartment where a recording electrode is located.

Circulating Long-Chain Acylcarnitine Concentrations are Not Affected by Exercise Training in Pregnant Women with Obesity

The purpose of this study was to determine the effect of exercise during pregnancy in sedentary women with obesity on longitudinal changes in long-chain acylcarnitine (LC-AC) concentrations. We hypothesized that exercise training would significantly decrease circulating LC-ACs throughout gestation compared to a non-exercise control group. Pregnant women with obesity considered otherwise healthy [n=80, mean ± SD; body mass index (BMI): 36.9±5.7 kg/m2] were randomized into an exercise (n=40, aerobic/resistance 3x/week, ~13th gestation week until birth) or a non-exercise control (n=40) group. At gestation week 12.2 ± 0.5 and 36.0 ± 0.4, a submaximal exercise test was conducted, and indirect calorimetry was used to measure relative resting energy expenditure (REE), as well as respiratory exchange ratio (RER) at rest. Fasting blood samples were collected and analyzed for LC-AC concentrations. Fitness improved with prenatal exercise training; however, exercise training did not affect circulating LC-AC. When groups were collapsed, LC-ACs decreased during gestation (combined groups, P < 0.001), whereas REE (kcal·kg-1·d-1, P = 0.008) increased. However, average REE relative to FFM (kcal·kgFFM-1·d-1) and RER did not change. There was an inverse relationship between the change in RER and all LC-ACs (except C18:2) throughout gestation (C14: r = -0.26, P = 0.04; C16: r = -0.27, P = 0.03; C18:1: r = -0.28, P = 0.02). In summary, a moderate intensity exercise intervention during pregnancy in women with obesity did not alter LC-ACs concentrations versus control, indicating that the balance between LCFA availability and oxidation neither improved nor worsened with an exercise intervention.

Administration of Particulate Oxygen Generators Improves Skeletal Muscle Contractile Function Following Ischemia-Reperfusion Injury in the Rat Hind Limb

Extended tourniquet application, often associated with battlefield extremity trauma, can lead to severe ischemia-reperfusion (I/R) injury in skeletal muscle. Particulate oxygen generators (POGs) can be directly injected into tissue to supply oxygen to attenuate the effects of I/R injury in muscle. The goal of this study was to investigate the efficacy of a sodium percarbonate (SPO)-based POG formulation in reducing ischemic damage in a rat hind limb during tourniquet application. Male Lewis rats were anesthetized and underwent tourniquet application for 3 hours, at a pressure of 300 mmHg. Shortly after tourniquet inflation animals received intramuscular injections of either 0.2 mg/mL SPO with catalase (n=6) or 2.0 mg/mL SPO with catalase (n=6) directly into the tibialis anterior (TA) muscle. An additional Tourniquet-Only group (n=12) received no intervention. Functional recovery was monitored using in vivo contractile testing of the hind limb at 1-, 2-, and 4-weeks post-injury. By the 4 week time point, the Low Dose POGs group continued to show improved functional recovery (85% of baseline) compared to the Tourniquet-Only (48%) and High Dose POG (56%) groups. In short, the Low Dose POGs formulation appeared, at least in part, to mitigate the impact of ischemic tissue injury, thus improving contractile function following tourniquet application. Functional improvement correlated with maintenance of larger muscle fiber cross sectional area, and the presence of fewer fibers containing centrally located nuclei. As such, POGs represent a potentially attractive therapeutic solution for addressing I/R injuries associated with extremity trauma.

Effects of time-controlled adaptive ventilation on cardiorespiratory parameters and inflammatory response in experimental emphysema

The time-controlled adaptive ventilation (TCAV) method attenuates lung damage in acute respiratory distress syndrome. However, so far, no study has evaluated the impact of the TCAV method on ventilator-induced lung injury (VILI) and cardiac function in emphysema. We hypothesized that the use of the TCAV method to achieve an expiratory flow termination/expiratory peak flow (EFT/EPF) of 25% could reduce VILI and improve right ventricular function in elastase-induced lung emphysema in rats. Five weeks after the last intratracheal instillation of elastase, animals were anesthetized and mechanically ventilated for 1 h using TCAV adjusted to either EFT/EPF 25% or EFT/EPF 75%, the latter often applied in ARDS. Pressure-controlled ventilation (PCV) groups with positive end-expiratory pressure levels similar to positive end-release pressure in TCAV with EFT/EPF 25% and EFT/EPF 75% were also analyzed. Echocardiography and lung ultrasonography were monitored. Lung morphometry, alveolar heterogeneity, and biological markers related to inflammation (interleukin [IL]-6, CINC-1), alveolar pulmonary stretch (amphiregulin), lung matrix damage (metalloproteinase [MMP]-9) were assessed. EFT/EPF 25% reduced respiratory system peak pressure, mean linear intercept, B lines at lung ultrasonography, and increased pulmonary acceleration time/pulmonary ejection time ratio compared with EFT/EPF 75%. The volume fraction of mononuclear cells, neutrophils, and expression of IL-6, CINC-1, amphiregulin, and MMP-9 were lower with EFT/EPF 25% than with EFT/EPF 75%. In conclusion, TCAV with EFT/EPF 25%, compared with EFT/EPF 75%, led to less lung inflammation, hyperinflation, and pulmonary arterial hypertension, which may be a promising strategy for patients with emphysema.