Journal of applied physiology最新文献

{"title":"Two paths to one destination: altered low-frequency oscillations of cerebral perfusion and oxygenation but not oxygen metabolism in mild cognitive impairment.","authors":"Leena N Shoemaker, Farah Kamar, Daniel Milej, Laura Fitzgibbon-Collins, Rasa Eskandari, Jaspreet Bhangu, J Kevin Shoemaker, Keith St Lawrence","doi":"10.1152/japplphysiol.00884.2024","DOIUrl":"10.1152/japplphysiol.00884.2024","url":null,"abstract":"<p><p>Cerebrovascular dysfunction, a risk factor for dementia, is challenging to detect in mild cognitive impairment (MCI). Herein, we used novel, light-based technology to investigate low-frequency hemodynamic oscillations (LFOs; 0.02-0.16 Hz) in cerebral perfusion, oxygenation, and relative metabolic rate of oxygen (rCMRO₂) in MCI (<i>n</i> = 13; 74 ± 6 yr) and cognitively intact controls (<i>n</i> = 10; 69 ± 6 yr). Relative cerebral microvascular perfusion and tissue oxygenation changes were recorded using a depth-enhanced optical monitoring system. Continuous wavelet transforms were used to compare average LFO power between groups (α = 0.025). Compared with controls, MCI had lower LFO power in microvascular perfusion, greater power in oxygenation (<i>P</i> ≤ 0.02), and no statistical difference in oscillatory power for rCMRO₂. Similar rCMRO₂ but opposing changes in oscillatory power for cerebral perfusion and oxygenation associated with MCI suggest an adaptation to maintain energy production.<b>NEW & NOTEWORTHY</b> We used a novel, depth-enhanced optical monitoring system to investigate low-frequency hemodynamic oscillations (0.02-0.16 Hz) in cerebral microvascular perfusion, oxygenation, and relative metabolic rate of oxygen in patients with MCI and cognitively intact controls. Our findings indicate cerebrovascular dysfunction in MCI, wherein the regulation of oxygenation is altered to maintain metabolism in an environment with attenuated vascular control. These findings highlight the potential of using optical technology to assess cerebrovascular function in MCI.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1361-1371"},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144063950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The non-nutritive sweetener erythritol adversely affects brain microvascular endothelial cell function.","authors":"Auburn R Berry, Samuel T Ruzzene, Emily I Ostrander, Kendra N Wegerson, Nathalie C Orozco-Fersiva, Madeleine F Stone, Whitney B Valenti, Joao E Izaias, Joshua P Holzer, Jared J Greiner, Vinicius P Garcia, Christopher A DeSouza","doi":"10.1152/japplphysiol.00276.2025","DOIUrl":"10.1152/japplphysiol.00276.2025","url":null,"abstract":"<p><p>The experimental aim of this study was to determine, in vitro, the effect of the non-nutritive sweetener erythritol on brain microvascular endothelial cell oxidative stress, nitric oxide (NO) and endothelin (ET)-1 production, as well as tissue-type plasminogen activator (t-PA) release. Human cerebral microvascular endothelial cells (hCMECs) were cultured and treated with 6 mM erythritol, equivalent to a typical amount of erythritol (30 g) in an artificially sweetened beverage, for 3 h. Intracellular reactive oxygen species (ROS) production was significantly higher in hCMECs treated with erythritol (204 ± 32% vs. 105 ± 4%) as well as the expression of antioxidant proteins, superoxide dismutase-1 [332.1 ± 16.2 vs. 214.9 ± 4.7 arbitrary units (AU); <i>P</i> = 0.002] and catalase (30.9 ± 0.3 vs. 24.4 ± 0.9 AU; <i>P</i> = 0.002). Although endothelial nitric oxide synthase (eNOS) expression was not significantly altered (102.8 ± 21.4 vs. 99.0 ± 19.9 AU); the expression of p-eNOS (Ser1177) was lower (52.1 ± 2.1 vs. 77.3 ± 9.1 AU; <i>P</i> < 0.001), and p-eNOS (Thr495) was higher (63.4 ± 8.0 vs. 45.6 ± 6.9 AU; <i>P</i> = 0.006) in hCMECs treated with erythritol. Cell expression of Big ET-1 was also higher in erythritol-treated cells (56.4 ± 9.8 vs. 40.9 ± 6.5 AU; <i>P</i> = 0.02). Consequently, the endothelial NO production was significantly lower (5.8 ± 0.8 vs. 7.3 ± 0.7 µmol/L) and ET-1 production was significantly higher (34.6 ± 2.3 vs. 26.9 ± 1.5 pg/mL) in response to erythritol. t-PA release in response to thrombin was significantly blunted in erythritol-treated (from 87.4 ± 6.3 to 87.6 ± 8.3 pg/mL) versus untreated (90.1 ± 5.5 to 110.2 ± 6.4 pg/mL) hCMECs. In summary, erythritol adversely affects oxidative stress, NO production, ET-1 production, and t-PA release in brain microvascular endothelial cells, potentially contributing to the increased risk of ischemic stroke associated with erythritol.<b>NEW & NOTEWORTHY</b> Erythritol, a common non-nutritive sweetener, is associated with increased risk of cardiovascular and cerebrovascular events. This study provides novel data, demonstrating that erythritol (at a concentration typically contained in a standard-size commercially available artificially sweetened beverage) adversely affects brain microvascular endothelial cell oxidative stress, eNOS activation and NO production, ET-1 expression, and t-PA release in vitro.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1571-1577"},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contributions of the peripheral respiratory chemoreceptors to hyperpnea at intensities below the respiratory compensation point.","authors":"Nasimi A Guluzade, Kira Nishidera, Robin Faricier, Brad J Matushewski, Daniel A Keir","doi":"10.1152/japplphysiol.00103.2025","DOIUrl":"10.1152/japplphysiol.00103.2025","url":null,"abstract":"<p><p>We evaluated the contribution of the peripheral chemoreflex to the breathing response during steady-state exercise at intensities below the respiratory compensation point (RCP). Eighteen healthy, young participants (nine females) completed a maximal exercise protocol (<i>visit 1</i>) and three step-incremental protocols (<i>visits 2-4</i>) over 4 days. The step-incremental protocol involved two 8-min stages in the lower and upper regions of the moderate-intensity domain (MOD₁ and MOD₂; below lactate threshold, LT) and two 12-min stages within the heavy-intensity domain (HVY₁ and HVY₂; between LT and RCP). Six-to-10 breaths of 100% oxygen were administered twice at rest and at three time points during steady-state exercise at each intensity (<i>visits 2</i> and <i>3</i>), and arterialized-venous blood samples were obtained for blood gases and metabolites (<i>visit 4</i>). Gas exchange and ventilatory variables were measured breath-by-breath by metabolic cart and pneumotach. Peripheral chemoreflex contribution was determined as the absolute change in minute ventilation (ΔV̇e) between the average of breaths between 10 and ∼20 s after O₂ breathing and those in the 30 s before O₂ breathing. The average ΔV̇e at rest was -0.3 ± 1.0 L·min^-1 and this value decreased to -2.7 ± 1.6 L·min^-1 at MOD₁, -4.2 ± 1.8 L·min^-1 at MOD₂, -5.8 ± 2.5 L·min^-1 at HVY₁, and -7.0 ± 2.7 L·min^-1 at HVY₂ (one-way ANOVA; <i>P</i> < 0.001). However, the intensity-dependent reduction in ΔV̇e was no longer significant when accounting for [H⁺] [one-way analysis of covariance (ANCOVA); <i>P</i> = 0.515]. Therefore, the peripheral chemoreflex drive to breathe (in L·min^-1) increases with exercise intensity below RCP and may stem from a reflexive response to rising [H⁺].<b>NEW & NOTEWORTHY</b> We assessed peripheral chemoreflex (PChR) contributions to steady-state breathing at rest and at four exercise intensities below the respiratory compensation point by quantifying the fall in ventilation in response to surreptitious oxygen breathing. The magnitude by which ventilation fell increased progressively from rest to the highest intensity, indicating a rising PChR drive. Proton concentration from arterialized-venous blood also increased with intensity. Intensity-dependent increases in PChR drive may reflect a reflexive response to rising proton concentration.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1372-1384"},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intraoperative evaluation of right ventricular mechanics in a pressure-overload swine model.","authors":"Francesco Paolo Lo Muzio, Birgit Zirngast, Barbara Karner, Martin Manninger, Mattia Fontana, Paul Steendijk, Heinrich Mächler, Giacomo Rozzi, Alessio Alogna","doi":"10.1152/japplphysiol.00143.2025","DOIUrl":"10.1152/japplphysiol.00143.2025","url":null,"abstract":"<p><p>Assessment of right ventricular (RV) mechanical performance during open chest surgery is typically based on invasive methods and subjective evaluations. This study developed a porcine model of acute progressive RV pressure overload to evaluate hemodynamic changes and validate the three- dimensional (3-D) video kinematic assessment of the videocardiograph (VCG). Seven healthy Landrace pigs were instrumented under fluoroscopic guidance with Swan-Ganz and RV conductance catheters. Following a median sternotomy, pulmonary artery banding (PB) was performed in two stages to induce minimal (PB_min) and maximal (PB_max) pressure overload. In a proof-of-concept experiment, different PB steps were performed to record both videos for the VCG and invasive pressure-volume assessments (PV loop). In addition, these videos were subjectively evaluated by five consultant surgeons, similar to clinical routine. PB_max significantly increased end-systolic pressure from baseline (21.1 ± 3.3 mmHg vs. 39.8 ± 7.8 mmHg, <i>P</i> = 0.001) and led to RV dilation, reduced ejection fraction (52.8 ± 10.3% vs. 33.9 ± 9.8%, <i>P</i> = 0.012), and decreased myocardial efficiency. In the proof-of-concept experiment, visual evaluations were highly variable among the cardiac surgeons, resulting in only a moderate reliability of their assessments (ICC = 0.59 for RV function; ICC = 0.60 for filling status). VCG-derived epicardial <i>z</i>-axis displacements, systolic timing, diastolic velocity, and volume demonstrated excellent relationships with PV loop data. This study established a porcine model of progressive RV pressure overload with robust PV loop assessment. VCG-derived epicardial kinematics reliably quantified RV mechanical activity and correlated with gold-standard hemodynamic measurements. This noninvasive, cost-effective method shows promise for early detection of acute RV dysfunction in the operating room and warrants further clinical investigation.<b>NEW & NOTEWORTHY</b> This study established a porcine model of acute right ventricular pressure overload using pulmonary artery banding to assess intraoperative RV mechanics. Hemodynamic changes were measured using pressure-volume (PV) loops and compared with 3-D video kinematic analysis from the videocardiograph (VCG). VCG-derived kinematic parameters correlated well with invasive PV loop data, whereas surgeons' visual assessments were highly variable. The findings suggest that VCG offers a reliable, noninvasive method for intraoperative RV function monitoring, warranting further clinical evaluation.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1560-1570"},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Skeletal muscle shape influences joint torque exertion through the mechanical advantages.","authors":"Jun Umehara, Masashi Taniguchi, Masahide Yagi, Ganping Li, Mazen Soufi, Yoshito Otake, Yoshinobu Sato, Yoshihiro Fukumoto, Momoko Yamagata, Ryusuke Nakai, Noriaki Ichihashi","doi":"10.1152/japplphysiol.00997.2024","DOIUrl":"10.1152/japplphysiol.00997.2024","url":null,"abstract":"<p><p>Skeletal muscle morphology is linked to its function. Extensive literature demonstrates that muscle volume is crucial for determining joint torque exertion, a primary function of muscle. However, whether muscle shape also influences torque exertion capacity remains unclear. This study illustrates that the three-dimensional shape of muscles independently determines joint torque exertion, irrespective of muscle volume, using a statistical shape model designed to quantify muscle shape features. The statistical shape model was developed from magnetic resonance images of the quadriceps femoris muscles in 33 healthy young adults (26 ± 5 yr; 18 males). We investigated the association between the shape components of each quadriceps femoris head and isometric knee extensor torque. The findings reveal that the mediolateral curvatures of the rectus femoris (<i>R</i>² = 0.60) and the bulging in the distal region of the vastus medialis (<i>R</i>² = 0.65) were associated with increased knee extensor torque despite muscle volumes. Moreover, the rectus femoris and vastus medialis shapes were correlated with the medial-directed line-of-action (<i>r</i> = -0.42 and ρ = -0.36). The vastus medialis shape was correlated with the moment arm of the patellar lateral spin (ρ = 0.45). Therefore, the three-dimensional muscle shape determines the joint torque exertion by forming the mechanical advantages that balance the force/torque output optimally. Our findings demonstrate that muscle shape is crucial in the mechanical output of skeletal muscle and provides a framework for enhancing the understanding of muscle morphology and its functionality.<b>NEW & NOTEWORTHY</b> Here, we developed a statistical shape model, a geometric model that can quantify muscle morphology, particularly the quadriceps femoris muscle, to determine the influence of three-dimensional muscle shape on its force-generating capacity in young adults. The results revealed that curvature of the rectus femoris and bulging of vastus medialis were determinants of isometric knee extension strength, coupled with their muscle volumes. This morphological functionality relies on the critical relationship between muscle shape and mechanical advantage.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1119-1132"},"PeriodicalIF":3.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of sympathetic vasomotor outflow during low-intensity leg cycling is attenuated in healthy older females.","authors":"Keisho Katayama, Kana Shiozawa, Koji Ishida, Ryoichi Banno, Akari Kinoshita, Erika Iwamoto, Shigehiko Ogoh","doi":"10.1152/japplphysiol.01008.2024","DOIUrl":"10.1152/japplphysiol.01008.2024","url":null,"abstract":"<p><p>The purpose of the present study was to elucidate the impact of age on muscle sympathetic nerve activity (MSNA) during dynamic leg exercise in females. Nine older females (71 ± 2 yr, means ± SD) and ten younger females (21 ± 2 yr) completed the study. The participants performed two 4-min leg cycling at 10% of their heart rate reserve using a cycle ergometer in a semirecumbent position [MSNA and estimated central venous pressure (eCVP) trials]. MSNA was recorded via microneurography of the left radial nerve. The CVP was estimated based on peripheral venous pressure, which was monitored using a cannula in the right antecubital vein. The magnitude of the change in mean arterial blood pressure during exercise was larger (<i>P</i> < 0.001) in older females (+11.6 ± 4.7 mmHg) compared with younger females (+4.1 ± 3.2 mmHg). MSNA burst frequency (BF) was decreased during cycling in both groups, but the magnitude of the decrease in MSNA BF was smaller (<i>P</i> = 0.004) in older females (-5.6 ± 1.8 bursts/min) than in younger females (-9.1 ± 2.5 bursts/min). The eCVP increased during exercise in both groups, and there was no difference in the changes in eCVP between the two groups (older, +0.80 ± 0.27 vs. younger, +1.02 ± 0.51 mmHg, <i>P</i> = 0.462). From these results, it is possible that the cardiopulmonary baroreflex-mediated inhibition of sympathetic vasomotor outflow, elicited by the muscle pump, may be attenuated with advancing age in females.<b>NEW & NOTEWORTHY</b> Aging does not affect the sympathoinhibitory effect of the cardiopulmonary baroreflex during low-intensity dynamic exercise in males; however, its impact on females remains unknown. The reduction in muscle sympathetic nerve activity burst frequency during low-intensity leg cycling was smaller in older females than in younger females, even with similar changes in estimated central venous pressure. In females, muscle pump-induced inhibition of sympathetic vasomotor outflow during leg cycling may be attenuated with advancing age.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1133-1142"},"PeriodicalIF":3.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Constitutively active mTORC1 signaling modifies the skeletal muscle metabolome and lipidome response to exercise.","authors":"Hanna Kalenta, Sean P Kilroe, Trevor B Romsdahl, Erik D Marchant, Rosario Maroto, Jennifer J Linares, William K Russell, Blake B Rasmussen","doi":"10.1152/japplphysiol.00987.2024","DOIUrl":"10.1152/japplphysiol.00987.2024","url":null,"abstract":"<p><p>A chronic increase in the Mammalian Target of Rapamycin Complex 1 (mTORC1) signaling is implicated in reduced longevity, altered metabolism, and mitochondrial dysfunction. Abnormal mTORC1 signaling may also be involved in the etiology of sarcopenia. To better understand the role of mTORC1 signaling in the regulation of muscle metabolism, we developed an inducible muscle-specific knockout model of DEP domain-containing 5 protein (DEPDC5 mKO), which results in constitutively active mTORC1 signaling. We hypothesized that constitutively active mTORC1 signaling in skeletal muscle would alter the metabolomic and lipidomic response to an acute bout of exercise. Wild-type (WT) and DEPDC5 muscle-specific knockout (KO) mice were studied at rest and following a 1 h bout of treadmill exercise. Acute exercise induced an increased reliance on glycolytic and pentose phosphate pathway (PPP) metabolites in the muscle of mice with hyperactive mTORC1. Lipidomic analysis showed an increase in triglycerides (TGs) in KO mice. Although exercise had a pronounced effect on muscle metabolism, the genotype effect was larger, indicating that constitutively active mTORC1 signaling exerts a dominant influence on metabolic and lipidomic regulation. We conclude that increased mTORC1 signaling shifts muscle metabolism toward greater reliance on nonoxidative energy sources in response to exercise. Understanding the mechanisms responsible for these effects may lead to the development of strategies for restoring proper mTORC1 signaling in conditions such as aging and sarcopenia.<b>NEW & NOTEWORTHY</b> This study demonstrates that hyperactive mTORC1 alters the muscle metabolomic and lipidomic response to exercise, with genotype having a larger effect than exercise. Knockout mice exhibited an increase in reliance on glycolysis and pentose phosphate pathway and an increase in triglyceride turnover. Wild-type mice primarily showed an increase in utilization of TCA cycle and lipid metabolism intermediates.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":"138 5","pages":"1173-1186"},"PeriodicalIF":3.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12236758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nalfurafine reverses fentanyl-induced muscle rigidity and respiratory depression without affecting sedation in rats: decoupling respiration from sedation.","authors":"Tristan Lewis, Philippe Haouzi","doi":"10.1152/japplphysiol.00952.2024","DOIUrl":"10.1152/japplphysiol.00952.2024","url":null,"abstract":"<p><p>This study examines whether nalfurafine, a κ-opioid receptor (κOR) agonist, reverses fentanyl-induced muscle rigidity and respiratory depression without impacting sedation. Adult, nonsedated Sprague-Dawley rats received intravenous fentanyl bolus injection (150 μg/kg), which induced immediate coma and muscle rigidity along with a transient central apnea, followed by sustained respiratory depression. Five minutes postfentanyl, rats were treated with saline, nalfurafine (0.1 or 1 mg/kg), or the κOR agonist U50488 (1 or 10 mg/kg). Muscle rigidity, sedation, and response to painful stimuli were assessed using blinded clinical scoring. Ventilation and pulmonary gas exchange were measured using open-flow body plethysmography. Nalfurafine at 1 mg/kg quickly and effectively reduced fentanyl-induced muscle rigidity, with a sustained effect throughout the 30-min observation period. Sedation scores remained consistent across all groups. In contrast to saline, nalfurafine (1 mg/kg) sharply increased minute ventilation V̇e, frequency (<i>f</i>), and tidal volume (Vt), which all plateaued at prefentanyl levels despite the animals remaining in a coma. V̇e/V̇o₂ and V̇e/V̇co₂ ratios also increased significantly compared with saline injection. U50488 at 1 mg/kg reversed muscle rigidity. Both nalfurafine (0.1 mg/kg) and U50488 at 1 mg/kg had a significantly weaker effect on ventilation than nalfurafine (1 mg/kg). At higher doses (10 mg/kg), U50488 after fentanyl was fatal. Nalfurafine is a promising therapeutic candidate able to reverse fentanyl-induced muscle rigidity and respiratory depression without affecting sedation or the response to painful stimuli, potentially improving the safety and efficacy of fentanyl in specific clinical settings. We could not, however, confirm that this effect was mediated via κOR.<b>NEW & NOTEWORTHY</b> Nalfurafine, a κ-opioid receptor (κOR) agonist, can reverse fentanyl-induced muscle rigidity and respiratory depression without affecting sedation. In nonanesthetized rats, nalfurafine (1 mg/kg) effectively reversed muscle rigidity and restored ventilation to prefentanyl levels even though the animals remained fully sedated. U50488, another κOR agonist, did not reproduce the results. These findings suggest that nalfurafine is a promising therapeutic to mitigate fentanyl's side effects while maintaining the benefits.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":"138 5","pages":"1161-1172"},"PeriodicalIF":3.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12118345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exercise-induced cardiovascular responses during combined normobaric versus hypobaric and normoxic versus hypoxic acute exposures in military air pilot trainee.","authors":"Nicolas Bourdillon, Mathias Roland Aebi, Denis Bron, Grégoire P Millet","doi":"10.1152/japplphysiol.00984.2024","DOIUrl":"10.1152/japplphysiol.00984.2024","url":null,"abstract":"<p><p>This study aimed to evaluate the putative effects of hypobaria on ventilatory, cardiovascular, and muscle oxygenation during exercise in normoxia and hypoxia. Eighteen healthy air pilot trainees (26 ± 3 yr, 177 ± 10 cm, 70 ± 11 kg) performed a 6-min moderate-intensity cycling exercise (1 W/kg) in four randomized conditions, namely, normobaric normoxia (NN), hypobaric normoxia (HN), normobaric hypoxia (NH), and hypobaric hypoxia (HH) in a hypobaric chamber. Inspired oxygen pressure was matched between normoxic (NN vs. HN, 141.2 ± 0.8 vs. 141.5 ± 1.5 mmHg) and hypoxic (NH vs. HH, 75.7 ± 0.4 vs. 74.3 ± 1.0 mmHg) conditions. Gas exchanges, pulse oxygen saturation ([Formula: see text]), heart rate, middle cerebral artery blood flow velocity, cerebral and muscular oxygenation, and cerebral O₂ delivery (cDO₂) were recorded. [Formula: see text], brain, and muscle oxygenation were significantly lower and ventilation higher in HH than in NN and HN, and NH, during both rest and exercise (exercise [Formula: see text] 99.0 ± 1.5, 80.8 ± 4.2, 97.6 ± 1.9, and 69.2 ± 5.7% and ventilation 12.5 ± 2.3, 13.3 ± 3.1, 12.4 ± 2.6, and 14.6 ± 2.4 L/min in NN, NH, HN, and HH, respectively). cDO₂ was decreased to the same extent in HH and NH compared with NN and HN (exercise 865.5 ± 147.6, 731.8 ± 152.2, 857.8 ± 157.8, and 755.8 ± 163.3 cm·mLO₂/s·dL_bl). Specific effects of hypobaria in normoxia were lesser than in hypoxia since only blood O₂ and CO₂ partial pressures were lower in HN than NN. Respiratory and cardiovascular responses and brain/muscle oxygenation were more altered in HH than in NH, which confirms the additive effects of hypobaria on exercise in severe hypoxia. However, the effects of hypobaria are likely of negligible clinical relevance in normoxia.<b>NEW & NOTEWORTHY</b> A hypobaric normoxia (HN) condition was used to disentangle the effects of hypoxia and hypobaria. There was an additive effect of hypobaria and hypoxia. Cerebral and muscular tissue oxygenation were lower in hypobaric normoxia than in normobaric hypoxia during rest and exercise. The effects of hypobaria were negligible in normoxia.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1109-1118"},"PeriodicalIF":3.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of heat acclimation on critical environmental limits and rate of rectal temperature change.","authors":"Timo van den Bogaard, Lisa Klous, Rachel M Cottle, Jan Van Erp, Hein A M Daanen","doi":"10.1152/japplphysiol.01004.2024","DOIUrl":"10.1152/japplphysiol.01004.2024","url":null,"abstract":"<p><p>Quantifying the effect of heat acclimation (HA) on critical wet-bulb globe temperature (WBGT_crit) and rate of rectal temperature change (vT_re) is relevant for developing guidelines with regards to occupational safety while working in warm environments. This study quantified the effect of HA and the period following cessation of the HA protocol on WBGT_crit and vT_re. Twenty-eight non-acclimatized participants were divided into a HA (<i>n</i> = 15) and control (CON; <i>n</i> = 13) group. The HA group underwent a warm-humid (35°C, 65% relative humidity) controlled hyperthermia HA protocol (5-9 days of achieving T_re ∼38.5°C for 60 min) and four progressive heat stress tests (HSTs) to identify WBGT_crit and examine vT_re: pre-, after 5 and 9 days of HA, and 4 to 8 days of no heat exposure following HA. CON performed two HSTs on average 13 days apart without heat exposure in between. HA increased WBGT_crit after nine (28.5 ± 2.7°C vs. 30.5 ± 2.0°C; <i>P</i> = 0.016) but not 5 days (28.5 ± 2.4; <i>P</i> > 0.05). No effect of HA on vT_re was observed (<i>P</i> > 0.05). Four-to-eight days post-HA, WBGT_crit and vT_re did not differ compared with 9 days of HA (<i>P</i> > 0.05). However, a reduction in vT_re (-0.4 ± 0.3 °C/h) was observed when comparing 4 to 8 days post-HA to pre-HA. In conclusion, our results demonstrate that more than 5 days of HA are required to increase WBGT_crit and indicate that 9 days of HA proceeded by adequate recovery reduced vT_re during exercise in the heat.<b>NEW & NOTEWORTHY</b> We assessed the effect of heat acclimation (HA) on critical environmental limits and rate of rectal temperature change. We show that more than 5 days of heat acclimation are required to increase critical environmental limits and that 9 days of HA proceeded by adequate recovery reduces the rate of rectal temperature change. These findings enhance our understanding of heat acclimation's effect on work capacity in the heat and may be used to design occupational guidelines.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1150-1160"},"PeriodicalIF":3.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}