Strategies to mitigate acute kidney injury risk during physical work in hot environments.

Prolonged physical work in the heat can reduce renal function and increase the risk of acute kidney injury (AKI). This is concerning given that the latest climate change projections forecast a rise in global temperature as well as the frequency, intensity, and duration of heatwaves. This means that outdoor and indoor workers in the agriculture or construction industries will be exposed to higher heat stress in the years ahead. Several studies indicate a higher incidence of chronic kidney disease from nontraditional origins (CKDnt) in individuals exposed to high temperatures, intense physical work, and/or recurrent dehydration. It has been proposed that prolonged physical work in the heat accompanied by dehydration results in recurrent episodes of AKI that ultimately lead to permanent kidney damage and the development of CKDnt. Thus, there is a need to identify and test strategies that can alleviate AKI risk during physical work in the heat. The purpose of this review is to present strategies that might prevent and mitigate the risk of AKI induced by physical work in the heat.

Plasma epinephrine and norepinephrine responses to extreme heat exposures in young and older adults.

Hyperthermia is known as a hyperadrenergic state, yet there is a lack of data on the sympathetic responses to ambient heat stress in humans. Therefore, we investigated the plasma epinephrine and norepinephrine concentrations of healthy young and older adults exposed to 3-hours of very-hot and dry and hot-humid heat, both with accompanying activities of daily living. We hypothesized that older adults, compared to young adults, would have augmented increases in epinephrine and norepinephrine concentrations secondary to increased thermal strain. Young (n=20) and older (n=18) participants underwent two 3-hour heat exposures on different days: very hot and dry (47°C and 15% RH) and hot and humid (41°C and 40% RH). To mimic heat generation comparable to activities of daily living, participants performed seven 5-minute bouts of light cycling (~3 METS) dispersed throughout the heat exposure. We measured plasma concentrations of epinephrine and norepinephrine at baseline, end, and 2hrs post-heat exposure. There was a group-wide increase in epinephrine from baseline to the end of the heat exposure (Δ19±27 pg/mL; p<0.001) in the hot and humid but not the very hot and dry condition (Δ6±19 pg/mL; p=0. 10 ). There were group-wide decreases in norepinephrine concentrations from baseline to the end of the heat exposure in both the very hot and dry (Δ-131±169 pg/mL; p<0.001) and the hot and humid (Δ-138±157 pg/mL; p<0.001) conditions, with both returning to near baseline at 2hrs post-exposure. These data suggest that ambient heating with accompanying bouts of light intermittent exercise may lead to decreases in circulating concentrations of norepinephrine.

Stimulated myotube contractions regulate membrane-bound and soluble TLR4 to prevent LPS-induced signaling and myotube atrophy in skeletal muscle cells.

Toll-like receptor 4 (TLR4) activation by lipopolysaccharides (LPS) increases proinflammatory cytokine production and upregulation of muscle atrophy signaling pathways. Muscle contractions can suppress LPS/TLR4 axis activation by reducing the protein expression of TLR4 on immune cells. However, the mechanism by which muscle contractions decrease TLR4 remains undefined. Moreover, it is not clear whether muscle contractions affect TLR4 expressed on skeletal muscle cells. The purpose of this study was to uncover the nature and mechanisms by which stimulated myotube contractions using electrical pulse stimulation (EPS) as an in vitro model of skeletal muscle contractions affect TLR4 expression and intracellular signaling to combat LPS-induced muscle atrophy. C2C12 myotubes were stimulated to contract via EPS with and without subsequent LPS exposure. We then examined the isolated effects of conditioned media (CM) collected following EPS and soluble TLR4 (sTLR4) alone on LPS-induced myotube atrophy. Exposure to LPS decreased membrane-bound and sTLR4, increased TLR4 signaling (decreased inhibitor of κBα), and induced myotube atrophy. However, EPS decreased membrane-bound TLR4, increased sTLR4, and prevented LPS-induced signaling and myotube atrophy. CM, which contained elevated levels of sTLR4, prevented LPS-induced upregulation of atrophy-related gene transcripts muscle ring finger 1 (MuRF1) and atrogin-1 and reduced myotube atrophy. Recombinant sTLR4 added to media prevented LPS-induced myotube atrophy. In summary, our study provides the first evidence that sTLR4 has anticatabolic effects by reducing TLR4-mediated signaling and atrophy. In addition, the study reveals a novel finding, by demonstrating that stimulated myotube contractions decrease membrane-bound TLR4 and increase the secretion of sTLR4 by myotubes.NEW & NOTEWORTHY Excessive Toll-like receptor 4 (TLR4) activation causes muscle atrophy. Muscle contractions can limit TLR4 activation on immune cells, but its impact on TLR4 expressed on skeletal muscle cells remains unclear. Here, we demonstrate in C2C12 myotubes for the first time that stimulated myotube contractions reduce membrane-bound TLR4 and increase soluble TLR4, preventing TLR4-mediated signaling and myotube atrophy. Further analyses revealed soluble TLR4 independently prevents myotube atrophy, supporting a potential therapeutic role in combating TLR4-mediated atrophy.

Effect of heat stress on heat shock protein expression and hypertrophy-related signaling in the skeletal muscle of trained individuals.

Muscle mass is balanced between hypertrophy and atrophy by cellular processes, including activation of the protein kinase B-mechanistic target of rapamycin (Akt-mTOR) signaling cascade. Stressors apart from exercise and nutrition, such as heat stress, can stimulate the heat shock protein A (HSPA) and C (HSPC) families alongside hypertrophic signaling factors and muscle growth. The effects of heat stress on HSP expression and Akt-mTOR activation in human skeletal muscle and their magnitude of activation compared with known hypertrophic stimuli are unclear. Here, we show a single session of whole body heat stress following resistance exercise increases the expression of HSPA and activation of the Akt-mTOR cascade in skeletal muscle compared with resistance exercise in a healthy, resistance-trained population. Heat stress alone may also exert similar effects, though the responses are notably variable and require further investigation. In addition, acute heat stress in C2C12 muscle cells enhanced myotube growth and myogenic fusion, albeit to a lesser degree than growth factor-mediated hypertrophy. Though the mechanisms by which heat stress stimulates hypertrophy-related signaling and the potential mechanistic role of HSPs remain unclear, these findings provide additional evidence implicating heat stress as a novel growth stimulus when combined with resistance exercise in human skeletal muscle and alone in isolated murine muscle cells. We believe these findings will help drive further applied and mechanistic investigation into how heat stress influences muscular hypertrophy and atrophy.NEW & NOTEWORTHY We show that acute resistance exercise followed by whole body heat stress increases the expression of HSPA and increases activation of the Akt-mTOR cascade in a physically active and resistance-trained population.

Exercise mitigates the Toll of muscle atrophy: a narrative review of the effects of exercise on Toll-like receptor-4 in leukocytes and skeletal muscle.

Conditions characterized by muscle wasting such as cachexia and sarcopenia are devastating at the individual level, and they place a profound burden on public health. Evidence suggests that inflammation is likely a mechanistic contributor to the pathogenesis of these conditions. One specific molecule, lipopolysaccharide, has gained attention due to its role in initiating inflammation. Toll-like receptor-4 is the primary receptor for lipopolysaccharide and has been shown to be implicit in the downstream proinflammatory response associated with lipopolysaccharide. Importantly, Toll-like receptor-4 is expressed in various cell types throughout the human body such as leukocytes and skeletal muscle fibers and may have site-specific effects that contribute to muscle wasting conditions based on the location in which activation occurs. Accordingly, reducing proinflammatory signaling at these locations may be an effective strategy at mitigating muscle wasting. Regular exercise training is believed to elicit anti-inflammatory adaptations, but the mechanisms by which this occurs are yet to be fully understood. Understanding the mechanisms by which Toll-like receptor-4 activation contributes to muscle wasting and how exercise affects this may allow for the development of a nonpharmacological therapeutic intervention. Therefore, in this review, we summarize the current understanding of the lipopolysaccharide/Toll-like receptor-4 axis in leukocytes and skeletal muscle fibers on the pathogenesis of muscle wasting conditions and we critically examine the current evidence regarding the effects of exercise on this axis.

High-altitude exposures and intestinal barrier dysfunction.

Gastrointestinal complaints are often reported during ascents to high altitude (>2,500 m), though their etiology is not known. One potential explanation is injury to the intestinal barrier which has been implicated in the pathophysiology of several diseases. High-altitude exposures can reduce splanchnic perfusion and blood oxygen levels causing hypoxic and oxidative stress. These stressors might injure the intestinal barrier leading to consequences such as bacterial translocation and local/systemic inflammatory responses. The purpose of this mini-review is to 1) discuss the impact of high-altitude exposures on intestinal barrier dysfunction and 2) present medications and dietary supplements which may have relevant impacts on the intestinal barrier during high-altitude exposures. There is a small but growing body of evidence which shows that acute exposures to high altitudes can damage the intestinal barrier. Initial data also suggest that prolonged hypoxic exposures can compromise the intestinal barrier through alterations in immunological function, microbiota, or mucosal layers. Exertion may worsen high-altitude-related intestinal injury via additional reductions in splanchnic circulation and greater hypoxemia. Collectively these responses can result in increased intestinal permeability and bacterial translocation causing local and systemic inflammation. More research is needed to determine the impact of various medications and dietary supplements on the intestinal barrier during high-altitude exposures.

Exercise in hypobaric hypoxia increases markers of intestinal injury and symptoms of gastrointestinal distress.

NEW FINDINGS: What is the central question of this study? What is the effect of hypobaric hypoxia on markers of exercise-induced intestinal injury and symptoms of gastrointestinal (GI) distress? What is the main finding and its importance? Exercise performed at 4300 m of simulated altitude increased intestinal fatty acid binding protein (I-FABP), claudin-3 (CLDN-3) and lipopolysaccharide binding protein (LBP), which together suggest that exercise-induced intestinal injury may be aggravated by concurrent hypoxic exposure. Increases in I-FABP, LBP and CLDN-3 were correlated to exercise-induced GI symptoms, providing some evidence of a link between intestinal barrier injury and symptoms of GI distress. ABSTRACT: We sought to determine the effect of exercise in hypobaric hypoxia on markers of intestinal injury and gastrointestinal (GI) symptoms. Using a randomized and counterbalanced design, nine males completed two experimental trials: one at local altitude of 1585 m (NORM) and one at 4300 m of simulated hypobaric hypoxia (HYP). Participants performed 60 min of cycling at a workload that elicited 65% of their NORM V̇O2max${\dot V_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$ . GI symptoms were assessed before and every 15 min during exercise. Pre- and post-exercise blood samples were assessed for intestinal fatty acid binding protein (I-FABP), claudin-3 (CLDN-3) and lipopolysaccharide binding protein (LBP). All participants reported at least one GI symptom in HYP compared to just one participant in NORM. I-FABP significantly increased from pre- to post-exercise in HYP (708 ± 191 to 1215 ± 518 pg ml-1 ; P = 0.011, d = 1.10) but not NORM (759 ± 224 to 828 ± 288 pg ml-1 ; P > 0.99, d = 0.27). CLDN-3 significantly increased from pre- to post-exercise in HYP (13.8 ± 0.9 to 15.3 ± 1.2 ng ml-1 ; P = 0.003, d = 1.19) but not NORM (13.7 ± 1.8 to 14.2 ± 1.6 ng ml-1 ; P = 0.435, d = 0.45). LBP significantly increased from pre- to post-exercise in HYP (10.8 ± 1.2 to 13.9 ± 2.8 µg ml-1 ; P = 0.006, d = 1.12) but not NORM (11.3 ± 1.1 to 11.7 ± 0.9 µg ml-1 ; P > 0.99, d = 0.32). I-FABP (d = 0.85), CLDN-3 (d = 0.95) and LBP (d = 0.69) were all significantly higher post-exercise in HYP compared to NORM (P ≤ 0.05). Overall GI discomfort was significantly correlated to ΔI-FABP (r = 0.71), ΔCLDN-3 (r = 0.70) and ΔLBP (r = 0.86). These data indicate that cycling exercise performed in hypobaric hypoxia can cause intestinal injury, which might cause some commonly reported GI symptoms.

Can linear regression confirm VO2max was attained in middle-aged and older adults?

PURPOSE: Evaluate the efficacy of a regression method for identifying a VO2 plateau to confirm the attainment of VO2max compared to a verification trial in middle-aged and older adults. METHODS: Eleven men and ten women (age 61.0 ± 8.1, VO2max 21.8-50.3 ml/kg/min, n = 21) completed an individualized ramp graded exercise test (GXT) on the cycle ergometer, and one hour later, a verification trial at 105% of their maximal work rate (WR) achieved during the GXT. A plateau in VO2 was used to confirm VO2max was attained. VO2 plateau was identified using the difference between the highest VO2 between the two trials and a linear regression analysis of the VO2-WR relationship during the GXT. McNemar's test of marginal homogeneity was used to detect differences in the proportion of paired data of individuals' attainment of VO2max criteria. RESULTS: Of the 21 participants, 15 (71.4%) met the verification criterion while 6 (28.6%) did not, compared to the regression method where 16 (76.2%) achieved the regression criterion while 5 (23.8%) did not. McNemar's test revealed no significant difference between participants' ability to achieve the regression and verification criteria (p = 0.999). CONCLUSION: The regression method is an effective strategy for confirming VO2max was attained with middle-aged and older adults on a cycle ergometer. This time-efficient regression method is comparable with the verification criterion but does not require a second maximal test, which may be advantageous for those where the verification trial may not be practical.

Kidney Function Biomarkers During Extreme Heat Exposure in Young and Older Adults.

This study investigates the effects of extreme heat exposure on kidney function using plasma-based biomarkers in young and older adults.

Effects of Exercise Induced Dehydration and Glycerol Rehydration on Anaerobic Power in Male Collegiate Wrestlers.

McKenna, ZJ and Gillum, TL. Effects of exercise induced dehydration and glycerol rehydration on anaerobic power in male collegiate wrestlers. J Strength Cond Res 31(11): 2965-2968, 2017-Wrestlers attempting to reach a specific weight class often use rapid weight loss (RWL). Rapid weight loss is associated with high levels of dehydration, which may hinder athletic performance. Thus, there is a need for wrestlers to optimize rehydration after achieving a specific weight. We sought to observe the effects of RWL on anaerobic power and the impact of glycerol on rehydration and power in male collegiate wrestlers (n = 7, 19.75 ± 1.67 years, 76.8 ± 4.32 kg, 11.6 ± 4.32% body fat, 59.9 ± 6.42 ml·kg·min). Subjects were assessed for body mass (BM), hydration, and mean power output (Wmean) before exercise (pre), immediately after exercise (3% dehydrated), and 60 minutes after exercise (rehydrated). Participants ran at 70% of V[Combining Dot Above]O2max in a heated room (30° C) until 3% BM loss (BML). Subjects rehydrated drinking either 26 ml·kg of water (control) or a 3% glycerol (treatment) solution containing 26 ml·kg of water and 1 g·kg of glycerol. Participants lost 3.00 ± 0.31% (control) and 2.89 ± 0.26% (treatment) of their BM from the pre- to dehydrated conditions. Wmean (control: 659.29 ± 79.12, 651.43 ± 70.71, 659.71 ± 82.78; treatment: 647.71 ± 110.64, 644.57 ± 118.15, 638.14 ± 100.71) did not differ across time (p = 0.87) nor condition (p = 0.80). In addition, glycerol had no significant impact on acute hydration (control: urine-specific gravity [SG] = 1.019 ± 0.010; treatment: SG = 1.017 ± 0.017). These data show that 3% BML did not impair anaerobic performance, and furthermore that glycerol proved ineffective for rehydration in a match like scenario for the competing wrestler.

Sports drinks do not increase acute kidney injury risk in males during industrial work in the heat when euhydration is maintained, a randomized crossover trial.

Industrial workers regularly perform physical labor under high heat stress, which may place them at risk for dehydration and acute kidney injury. Current guidelines recommend that workers should consume sports drinks to maintain euhydration during work shifts. However, the impact of fructose sweetened sports drinks on acute kidney injury risk is unknown. The purpose of this study was to investigate the effects of sports drink consumption on markers of acute kidney injury following simulated industrial work in the heat. Twenty males completed two matched 2 h simulated industrial work trial visits in a warm and humid environment (30 °C and 55% relative humidity). During and following the bout of simulated work, participants consumed either a commercially available sports drink or a noncaloric placebo. Urine and blood samples, collected pre-, post-, and 16 h post-work were assayed for markers of hydration (plasma/urine osmolality, and urine specific gravity) and acute kidney injury (KIM-1 and NGAL). There were no differences in physiological or perceptual responses to the bout of work (interaction p > 0.05 for all indices), and markers of hydration were similar between trials (interaction p > 0.05 for all indices). KIM-1 (Placebo: Δ Ln 1.18 ± 1.64; Sports drink: Δ Ln 1.49 ± 1.10 pg/mL; groupwide d = 0.89, p < 0.001) and NGAL (Placebo: Δ Ln 0.44 ± 1.11; Sports drink: Δ Ln 0.67 ± 1.22 pg/mL; groupwide d = 0.39, p = 0.03) were elevated pre- to post-work, but there were no differences between trials (interaction p > 0.05). These data provide no evidence that consumption of fructose sweetened sports drinks increases the risk of acute kidney injury during physical work in the heat.

Divergent mechanisms regulate TLR4 expression on peripheral blood mononuclear cells following workload-matched exercise in normoxic and hypoxic environments.

Exercise in hypoxia increases immune responses compared with normoxic exercise, and while Toll-like receptor 4 (TLR4) is implicated in these responses, its regulation remains undefined. The purpose of this study was to 1) investigate TLR4 regulation during workload-matched endurance exercise in normoxic and hypoxic conditions in vivo and 2) determine the independent effects of hypoxia and muscle contractions on TLR4 expression in vitro. Eight recreationally active men cycled for 1 h at 65% of their V̇o2max in normoxia (630 mmHg) and in hypobaric hypoxia (440 mmHg). Exercise in normoxia decreased TLR4 expressed on peripheral blood mononuclear cells (PBMCs), had no effect on the expression of inhibitor of κBα (IκBα), and increased the concentration of soluble TLR4 (sTLR4) in circulation. In contrast, exercise in hypoxia decreased the expression of TLR4 and IκBα in PBMCs, and sTLR4 in circulation. Markers of physiological stress were higher during exercise in hypoxia, correlating with markers of intestinal barrier damage, circulating lipopolysaccharides (LPS), and a concurrent decrease in circulating sTLR4, suggesting heightened TLR4 activation, internalization, and degradation in response to escalating physiological strain. In vitro, both hypoxia and myotube contractions independently, and in combination, reduced TLR4 expressed on C2C12 myotubes, and these effects were dependent on hypoxia-inducible factor 1 (HIF-1). In summary, the regulation of TLR4 varies depending on the physiological stress during exercise. To our knowledge, our study provides the first evidence of exercise-induced effects on sTLR4 in vivo and highlights the essential role of HIF-1 in the reduction of TLR4 during contraction and hypoxia in vitro.NEW & NOTEWORTHY We provide the first evidence of exercise affecting soluble Toll-like receptor 4 (sTLR4), a TLR4 ligand decoy receptor. We found that the degree of exercise-induced physiological stress influences TLR4 regulation on peripheral blood mononuclear cells (PBMCs). Moderate-intensity exercise reduces PBMC TLR4 and increases circulating sTLR4. Conversely, workload-matched exercise in hypoxia induces greater physiological stress, intestinal barrier damage, circulating lipopolysaccharides, and reduces both TLR4 and sTLR4, suggesting heightened TLR4 activation, internalization, and degradation under increased strain.

Sex Differences in Sympathetic Responses to Lower-Body Negative Pressure.

INTRODUCTION: Trauma-induced hemorrhage is a leading cause of death in prehospital settings. Experimental data demonstrate that females have a lower tolerance to simulated hemorrhage (i.e., central hypovolemia). However, the mechanism(s) underpinning these responses are unknown. Therefore, this study aimed to compare autonomic cardiovascular responses during central hypovolemia between the sexes. We hypothesized that females would have a lower tolerance and smaller increase in muscle sympathetic nerve activity (MSNA) to simulated hemorrhage. METHODS: Data from 17 females and 19 males, aged 19-45 yr, were retrospectively analyzed. Participants completed a progressive lower-body negative pressure (LBNP) protocol to presyncope to simulate hemorrhagic tolerance with continuous measures of MSNA and beat-to-beat hemodynamic variables. We compared responses at baseline, at two LBNP stages (-40 and -50 mmHg), and at immediately before presyncope. In addition, we compared responses at relative percentages (33%, 66%, and 100%) of hemorrhagic tolerance, calculated via the cumulative stress index (i.e., the sum of the product of time and pressure at each LBNP stage). RESULTS: Females had lower tolerance to central hypovolemia (female: 561 ± 309 vs male: 894 ± 304 min·mmHg [time·LBNP]; P = 0.003). At LBNP -40 and -50 mmHg, females had lower diastolic blood pressures (main effect of sex: P = 0.010). For the relative LBNP analysis, females exhibited lower MSNA burst frequency (main effect of sex: P = 0.016) accompanied by a lower total vascular conductance (sex: P = 0.028; main effect of sex). CONCLUSIONS: Females have a lower tolerance to central hypovolemia, which was accompanied by lower diastolic blood pressure at -40 and -50 mmHg LBNP. Notably, females had attenuated MSNA responses when assessed as relative LBNP tolerance time.

Impact of Maternal Exercise on Mice Offspring Development, Pulmonary Hypertension, and Vascular Remodeling in Chronic Hypoxia.

PURPOSE: Chronic, high-altitude hypoxic exposure increases the risk of high-altitude pulmonary hypertension (PH). Emerging evidence shows maternal exercise may improve offspring resistance to disease throughout life. The purpose of this study is to determine if maternal exercise mitigates chronic hypoxic-induced changes in the offspring indicative of high-altitude pulmonary hypertension development. METHODS: Female adult C57BL/6 J mice were randomly allocated to nonexercise or exercise conditions. Exercise consisted of voluntary running wheel exercise for four weeks during the perinatal period. Three days after birth, the pups remained at low altitude (normoxia) or were exposed to hypobaric hypoxia of 450 mmHg to simulate ~4500 m altitude exposure until 8 weeks of age. The study consisted of 4 groups: Hypoxia + Nonexercise pregnancy, Hypoxia + Exercise, or the respective, normoxia conditions (Normoxia + Nonexercise or Normoxia + Exercise). Offspring body size, motor function, right ventricular systolic pressure (RVSP), and cardiopulmonary morphology were assessed after 8 weeks in normoxia or hypoxia. RESULTS: Both hypoxic groups had smaller body sizes, reduced motor function, increased hematocrit, RVSP, muscularization in medium-sized pulmonary arteries, as well as right ventricular hypertrophy and contractility compared to the normoxic groups ( p < 0.05). CONCLUSIONS: Chronic hypoxia simulating 4500 m attenuated growth, lowered motor function, and elicited PH development. Voluntary maternal exercise did not significantly decrease RVSP in the offspring, which aligned with a lack of effect to attenuate abnormal body size and cardiopulmonary development due to chronic hypoxia. These findings are preliminary in nature and more powered studies through larger group sizes are required to generalize the results to the population.

Aging Increases Enterocyte Damage during a 3-Hour Exposure to Very Hot and Dry Heat: A Preliminary Study.

Profound heat stress can damage the gastrointestinal barrier, leading to microbial translocation from the gut and subsequent systemic inflammation. Despite the greater vulnerability of older people to heat wave-related morbidity and mortality, it is unknown if age modulates gastrointestinal barrier damage and inflammation during heat stress. Therefore, the aim of this study was to determine if aging impacted enterocyte damage and systemic inflammatory responses to a 3-h exposure to very hot and dry (47 °C, 15% humidity) heat with accompanying activities of daily living (intermittent activity at 3 METS). Data from 16 young (age 21 to 39 years) and 16 older (age 65 to 76 years) humans were used to address this aim. In each group, log-transformed plasma concentrations of intestinal fatty acid binding protein (I-FABPlog), interleukin-8 (IL-8log), and tissue factor (TFlog) were assessed as indices of enterocyte damage, systemic inflammation, and blood coagulation, respectively, before and after the 3-h heat exposure. In the younger cohort, I-FABPlog concentration did not increase from pre to post heat exposure (p = 0.264, d = 0.20), although it was elevated in the older group (p = 0.014, d = 0.67). The magnitude of the increase in I-FABPlog was greater in the older participants (p = 0.084, d = 0.55). Across all participants, there was no correlation between the change in core temperature and the change in IFABPlog. There was no change in IL-8log in the younger group (p = 0.193, d = 0.23) following heat exposure, but we observed a decrease in IL-8log in the older group (p = 0.047, d = 0.48). TFlog decreased in the younger group (p = 0.071, d = 0.41), but did not change in the older group (p = 0.193, d = 0.15). Our data indicate that I-FABPlog concentration (an index of enterocyte damage) is increased in older humans during a 3-h extreme heat exposure. Future studies should determine whether this marker reflects increased gastrointestinal barrier permeability in older individuals during heat exposure.

Autophagy in peripheral blood mononuclear cells is associated with body fat percentage.

CONTEXT: Numerous chronic conditions including obesity exhibit autophagic dysfunction. Association of immune cell autophagic marker regulation by body fat percentage (%BF) is unknown. OBJECTIVE: Investigate autophagy activity in peripheral blood mononuclear cells (PBMCs) of adults with distinct %BFs and obesity-related circulating inflammatory markers. MATERIALS AND METHODS: Sixteen individuals (eight males) with %BF above (n = 8, 36.9 ± 3.6 years, 27.1 ± 8.1%BF) and below (n = 8, 37.1 ± 3.7 years, 13.3 ± 3.7%BF) their age- and sex-specific 50th percentile value based on the American College Sports Medicine guidelines participated. Body fat percentage was calculated from hydrostatic weighing. PBMCs were isolated from venous blood, and PBMC autophagic flux markers (LC3-I, LC3-II, and p62) were measured via Western blot. CRP, resistin, leptin, and adiponectin were measured via ELISA. RESULTS: LC3-II/LC3-I ratio correlated with %BF (r=-0.56, p=.023). Insulin (p=.05) and CRP (p=.018) were higher in high %BF participants. DISCUSSION AND CONCLUSIONS: Autophagic activity markers in PBMCs correlate with %BF, but are not different between %BF groups.

Age alters the thermoregulatory responses to extreme heat exposure with accompanying activities of daily living.

Older adults are at greater risk for heat-related morbidity and mortality, due in part to age-related reductions in heat dissipating capabilities. Previous studies investigating the impact of age on responses to heat stress used approaches that lack activities of daily living and therefore may not accurately depict the thermal/physiological strain that would occur during actual heatwaves. We sought to compare the responses of young (18-39 yr) and older (≥65 yr) adults exposed to two extreme heat simulations. Healthy young (n = 20) and older (n = 20) participants underwent two 3-h extreme heat exposures on different days: 1) DRY (47°C and 15% humidity) and 2) HUMID (41°C and 40% humidity). To mimic heat generation comparable with activities of daily living, participants performed 5-min bouts of light physical activity dispersed throughout the heat exposure. Measurements included core and skin temperatures, heart rate, blood pressure, local and whole body sweat rate, forearm blood flow, and perceptual responses. Δ core temperature (Young: 0.68 ± 0.27°C vs. Older: 1.37 ± 0.42°C; P < 0.001) and ending core temperature (Young: 37.81 ± 0.26°C vs. Older: 38.15 ± 0.43°C; P = 0.005) were greater in the older cohort during the DRY condition. Δ core temperature (Young: 0.58 ± 0.25°C vs. Older: 1.02 ± 0.32°C; P < 0.001), but not ending core temperature (Young: 37.67 ± 0.34°C vs. Older: 37.83 ± 0.35°C; P = 0.151), was higher in the older cohort during the HUMID condition. We demonstrated that older adults have diminished thermoregulatory responses to heat stress with accompanying activities of daily living. These findings corroborate previous reports and confirm epidemiological data showing that older adults are at a greater risk for hyperthermia.NEW & NOTEWORTHY Using an experimental model of extreme heat exposure that incorporates brief periods of light physical activity to simulate activities of daily living, the extent of thermal strain reported herein more accurately represents what would occur during actual heatwave conditions. Despite matching metabolic heat generation and environmental conditions, we show that older adults have augmented core temperature responses, likely due to age-related reductions in heat dissipating mechanisms.

Attrition of Well-Healed Burn Survivors to a 6-Month Community-Based Exercise Program: A Retrospective Evaluation.

The purpose of this study was to evaluate whether burn survivors have lower adherence compared to non-burned control individuals during a 6-month community-based exercise program. In burn survivors, we sought to answer if there was a relation between the size of the burn injury and dropout frequency. Fifty-two burn survivors and 15 non-burned controls (n = 67) were recruited for a 6-month community-based (ie, non-supervised), progressive, exercise training program. During the exercise program, 27% (ie, 4 of the 15 enrolled) of the non-burned individuals dropped out of the study, while 37% (ie, 19 of the 52) of the burn survivors dropped out from the study. There was no difference in the percentage of individuals who dropped out between groups (P = .552). There was no difference in size of the burn injury, expressed as percent body surface area burned (%BSA) between the burn survivors that dropped out versus those who completed the exercise regimen (P = .951). We did not observe a relation between %BSA burned and dropouts (log odds = -0.15-0.01(%BSA), B = -0.01, SE = 0.015, P = .541). There was no effect of %BSA burned on the probability of dropout [Exp (B) = 0.991, 95% CI (0.961, 1.020)] and there were no differences in the percentage of individuals who dropped out of the study based on %BSA burned (χ2(1) = 0.44, P = .51). These data demonstrate that burn survivors have similar exercise adherence relative to a non-burned group and the extent of a burn injury does not affect exercise program adherence.

Cardiac remodeling in well-healed burn survivors after 6 months of unsupervised progressive exercise training.

Aerobic exercise is important in the rehabilitation of individuals with prior burn injuries, but no studies have examined whether adult burn survivors demonstrate cardiac remodeling to long-term aerobic exercise training. In this study, we tested the hypothesis that 6 months of progressive exercise training improves cardiac magnetic resonance imaging-based measures of cardiac structure and function in well-healed burn survivors. Secondary analyses explored relations between burn surface area and changes in cardiac structure in the cohort of burn survivors. V̇o2peak assessments and cardiac magnetic resonance imaging were performed at baseline and following 6 months of progressive exercise training from 19 well-healed burn survivors and 10 nonburned control participants. V̇o2peak increased following 6 months of training in both groups (Control: Δ5.5 ± 5.8 mL/kg/min; Burn Survivors: Δ3.2 ± 3.6 mL/kg/min, main effect of training, P < 0.001). Left ventricle (LV) mass (Control: Δ1.7 ± 3.1 g/m2; Burn survivors: Δ1.8 ± 2.7 g/m2), stroke volume (Control: Δ5.8 ± 5.2 mL/m2; Burn Survivors: Δ2.8 ± 4.2 mL/m2), and ejection fraction (Control: Δ2.4 ± 4.0%; Burn Survivors: Δ2.2 ± 4.3%) similarly increased following 6 months of exercise training in both cohorts (main effect of training P < 0.05 for all indexes). LV end-diastolic volume increased in the control group (Δ6.5 ± 4.5 mL/m2) but not in the cohort of burn survivors (Δ1.9 ± 2.7 mL/m2, interaction, P = 0.040). Multiple linear regression analyses revealed that burn surface area had little to no effect on changes in ventricular mass or end-diastolic volumes in response to exercise training. Our findings provide initial evidence of physiological cardiac remodeling, which is not impacted by burn size, in response to exercise training in individuals with well-healed burn injuries.NEW & NOTEWORTHY Aerobic exercise is important in the rehabilitation of individuals with prior burn injuries, but no studies have examined whether adult burn survivors demonstrate cardiac remodeling to long-term aerobic exercise training. In this study, we tested the hypothesis that 6 months of progressive exercise training would improve cardiac magnetic resonance imaging-based measures of cardiac structure and function in well-healed burn survivors. Our findings highlight the ability of exercise training to modify cardiac structure and function in well-healed burn survivors and nonburned sedentary controls alike.

Ibuprofen Increases Markers of Intestinal Barrier Injury But Suppresses Inflammation at Rest and After Exercise in Hypoxia.

PURPOSE: The purpose of this study was to evaluate the effects of acute ibuprofen consumption (2 × 600-mg doses) on markers of enterocyte injury, intestinal barrier dysfunction, inflammation, and symptoms of gastrointestinal (GI) distress at rest and after exercise in hypobaric hypoxia. METHODS: Using a randomized double-blind placebo-controlled crossover design, nine men (age, 28 ± 3 yr; weight, 75.4 ± 10.5 kg; height, 175 ± 7 cm; body fat, 12.9% ± 5%; V̇O 2 peak at 440 torr, 3.11 ± 0.65 L·min -1 ) completed a total of three visits including baseline testing and two experimental trials (placebo and ibuprofen) in a hypobaric chamber simulating an altitude of 4300 m. Preexercise and postexercise blood samples were assayed for intestinal fatty acid binding protein (I-FABP), ileal bile acid binding protein, soluble cluster of differentiation 14, lipopolysaccharide binding protein, monocyte chemoattractant protein-1, tumor necrosis factor α (TNF-α), interleukin-1ß, and interleukin-10. Intestinal permeability was assessed using a dual sugar absorption test (urine lactulose-to-rhamnose ratio). RESULTS: Resting I-FABP (906 ± 395 vs 1168 ± 581 pg·mL -1 ; P = 0.008) and soluble cluster of differentiation 14 (1512 ± 297 vs 1642 ± 313 ng·mL -1 ; P = 0.014) were elevated in the ibuprofen trial. Likewise, the urine lactulose-to-rhamnose ratio (0.217 vs 0.295; P = 0.047) and the preexercise to postexercise change in I-FABP (277 ± 308 vs 498 ± 479 pg·mL -1 ; P = 0.021) were greater in the ibuprofen trial. Participants also reported greater upper GI symptoms in the ibuprofen trial ( P = 0.031). However, monocyte chemoattractant protein-1 ( P = 0.007) and TNF-α ( P = 0.047) were lower throughout the ibuprofen trial compared with placebo (main effect of condition). CONCLUSIONS: These data demonstrate that acute ibuprofen ingestion aggravates markers of enterocyte injury and intestinal barrier dysfunction at rest and after exercise in hypoxia. However, ibuprofen seems to suppress circulating markers of inflammation.