{"title":"Microphysiological systems to advance human pathophysiology and translational medicine.","authors":"Anicca D Harriot, Christopher W Ward, Deok-Ho Kim","doi":"10.1152/japplphysiol.00087.2024","DOIUrl":"10.1152/japplphysiol.00087.2024","url":null,"abstract":"<p><p>Microphysiological systems (MPS) or \"organ-on-a-chip\" models are sophisticated tools that harness techniques from cell biology, tissue engineering, and microengineering to recapitulate human physiology. Typically, MPS are biofabricated three-dimensional (3-D) tissue constructs integrated into platforms designed to mimic the tissue microenvironment and provide functional outputs. Over the past decade, researchers have endeavored to manufacture high-throughput, high-fidelity MPS models of all major human organs. By incorporating patient-derived cells, researchers have produced biomimetic models of tissues with disease-linked genetic mutations capable of exhibiting patient heterogeneity. This work has demonstrated that MPS more closely model organotypic function and pathophysiology than traditional two-dimensional (2-D) culture systems. Moreover, investigators have shown that human MPS are better predictors of drug efficacy and toxicity than animal models. Thus, MPS have emerged as a promising candidate to improve the efficacy and safety of preclinical trials. In this mini-review, we provide an overview of current advances in MPS models, their applications in mechanistic research, and relevance to drug screening. Finally, we discuss current investments in MPS development by the United States federal government and research institutions around the world to advance translational medicine.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1494-1501"},"PeriodicalIF":3.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466238","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}
Filip Konecny, Lujaina Kamar, Isabel Zimmerman, Shawn N Whitehead, Daniel Goldman, Jefferson C Frisbee
{"title":"Early elevations in arterial pressure: a contributor to rapid depressive symptom emergence in female Zucker rats with metabolic disease?","authors":"Filip Konecny, Lujaina Kamar, Isabel Zimmerman, Shawn N Whitehead, Daniel Goldman, Jefferson C Frisbee","doi":"10.1152/japplphysiol.00586.2024","DOIUrl":"10.1152/japplphysiol.00586.2024","url":null,"abstract":"<p><p>One of the growing challenges to public health and clinical outcomes is the emergence of cognitive impairments, particularly depressive symptom severity, because of chronic elevations in metabolic disease and cerebrovascular disease risk. To more clearly delineate these relationships and to assess the potential for sexual dimorphism, we used lean (LZR) and obese Zucker rats (OZR) of increasing age to determine relationships between internal carotid artery (ICA) hemodynamics, cerebral vasculopathies, and the emergence of depressive symptoms. Male OZR exhibited progressive elevations in perfusion pressure within the ICA, which were paralleled by endothelial dysfunction, increased cerebral arterial myogenic activation, and reduced cerebral cortex microvessel density. In contrast, female OZR exhibited a greater degree of ICA hypertension than male OZR but maintained normal endothelial function, myogenic activation, and microvessel density to an older age range than did males. Although both male and female OZR exhibited significant and progressive elevations in depressive symptom severity, these were significantly worse in females. Finally, plasma cortisol concentration was elevated higher and at a younger age in female OZR as compared with males, and this difference was maintained to final animal usage at ∼17 wk of age. These results suggest that an increased severity of blood pressure waves may penetrate the cerebral circulation more deeply in female OZR than in males, which may predispose the females to a more severe emergence of depressive symptoms with chronic metabolic disease, whereas males may be more predisposed to more direct cerebral vasculopathies (e.g., stroke, transient ischemic attack).<b>NEW & NOTEWORTHY</b> We provide novel insight that the superior maintenance of cerebrovascular endothelial function in female versus male rats with chronic metabolic disease buffers myogenic activation of cerebral resistance arteries/arterioles despite worsening hypertension. As hypertension development is earlier and more severe in females, potentially due to an elevated stress response, the blunted myogenic activation allows greater arterial pressure wave penetrance into the cerebral microcirculation and is associated with accelerated emergence/severity of depressive symptoms in obese female rats.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1324-1340"},"PeriodicalIF":3.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11573269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365350","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}
Warwick M Bayly, Renaud Leguillette, Raymond H Sides, Shannon Massie, Charline Guigand, K Blythe Jones, Linnea M Warlick, Emily L Thueson, Tristan A Troudt, Ronald F Slocombe, James H Jones
{"title":"Equine exercise-induced pulmonary hemorrhage: the role of high left-heart pressures secondary to exercise-induced hypervolemia, and high inspiratory pressures.","authors":"Warwick M Bayly, Renaud Leguillette, Raymond H Sides, Shannon Massie, Charline Guigand, K Blythe Jones, Linnea M Warlick, Emily L Thueson, Tristan A Troudt, Ronald F Slocombe, James H Jones","doi":"10.1152/japplphysiol.00575.2023","DOIUrl":"10.1152/japplphysiol.00575.2023","url":null,"abstract":"<p><p>Exercise-induced pulmonary hemorrhage (EIPH) is common in racehorses. Stress failure of the blood-gas barrier causes EIPH when the transmural pulmonary capillary (Pcap)-alveolar pressure difference (Ptm) exceeds the barrier's stress failure threshold. Why Pcap increases is incompletely understood. We hypothesized that alterations in blood volume (BV) could affect left ventricular (LV) and pulmonary arterial wedge (PAW) pressures and Pcap, and correspondingly affect EIPH severity. Six thoroughbreds with EIPH exercised at the same treadmill speed (≈11.9 m/s [11.1, 12.2]; median [IQR]) before (≈119% V̇o<sub>2max</sub>; B), 2 h after 14 L depletion of blood (≈132% V̇o<sub>2max</sub>; D), and 2 h after reinfusing the blood (≈111% V̇o<sub>2max</sub>; R). LV, pulmonary arterial (PAP), PAW, and intrapleural (Ppl) pressures were measured throughout exercise. Pcap = (PAP + PAW)/2 and Ptm = (Pcap - Ppl). EIPH severity was assessed 60 min postexercise by tracheoendoscopy (EIPHgrade) and bronchoalveolar lavage erythrocyte number (BALRBC). A mixed-effect model and Tukey post hoc test analyzed the effects of BV changes on LV, PAW, Pcap, Ppl, Ptm, and EIPH. <i>P</i> ≤ 0.05 was significant. Peak intrapleural inspiratory pressure (Ppl<sub>I</sub>) was high (-41 mmHg), unaffected by changes in BV (<i>P</i> = 0.44), and did not contribute to fluctuations in Ptm and EIPH severity, whereas changes in BV did (EIPHgrade: <i>P</i> = 0.01, BALRBC: <i>P</i> = 0.003). EIPH prevalence was 100% with B and R but 50% with D. MaxPtm was not different between B (146 mmHg [140, 151]) and R (151 mmHg [137, 160]) but was lower for D (128 mmHg [127, 130]; B: <i>P</i> = 0.005, R: <i>P</i> = 0.02). Vascular pressures and Ppl fluctuated constantly during exercise and independently influenced Ptm. Left ventricular end diastolic (LVED) pressure was correlated with Ptm (<i>r</i><sub>rm</sub> = 0.90, <i>P</i> = 0.03) and EIPH <i>r</i><sub>rm</sub> = 0.82, <i>P</i> = 0.004). Exercise BV was strongly correlated with EIPH severity in racehorses (<i>r</i><sub>rm</sub> = 0.86, <i>P</i> = 0.009).<b>NEW & NOTEWORTHY</b> Hypervolemia induced by the infusion of erythrocyte-rich blood stored in the spleen is normal in high-speed thoroughbred exercise and increases capillary-alveolar transmural pressure (Ptm), leading to exercise-induced pulmonary hemorrhage (EIPH). In this study, decreasing blood volume reduced Ptm and EIPH. Large negative inspiratory pressures also contribute to high Ptm and the occurrence of EIPH. Ptm is dynamic and oscillates constantly during exercise. A significant relationship existed between circulating blood volume and EIPH severity in racehorses.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1359-1373"},"PeriodicalIF":3.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11573257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400372","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}
Robert A Dowden, Lee J Kerkhof, Paul J Wisniewski, Max M Häggblom, Sara C Campbell
{"title":"Temporal changes in the mouse gut bacteriota influenced by host sex, diet, and exercise.","authors":"Robert A Dowden, Lee J Kerkhof, Paul J Wisniewski, Max M Häggblom, Sara C Campbell","doi":"10.1152/japplphysiol.00487.2023","DOIUrl":"10.1152/japplphysiol.00487.2023","url":null,"abstract":"<p><p>The gut microbiota plays an important role in host physiology. However, the effects of host sex, lifestyle, and temporal influences on the bacterial community within the gut remain ill-defined. To address this gap, we evaluated 56 male and female mice over a 10-wk study to assess the effects of sex, diet, and exercise on gut community dynamics. Mice were randomly assigned to high-fat or control diet feeding and had free access to running wheels or remained sedentary throughout the study period. The fecal bacterial community was characterized by rRNA operon profiling via nanopore sequencing. Differential abundance testing indicated that ∼200 bacterial taxa were significantly influenced by sex, diet, or exercise (4.2% of total community), which also changed over time (82 taxa, 1.7% of total community). Phylogenetic analysis of taxa closely related to <i>Dysosmobacter welbionis</i>, and several members of the family Muribaculaceae were examined more closely and demonstrated distinct species/strain level subclustering by host sex, diet, and exercise. Collectively, these data suggest that sex and lifestyle can alter the gut bacteriota at the species/strain level that may play a role in host health. These results also highlight the need for improved characterization methods to survey microbial communities at finer taxonomic resolution.<b>NEW & NOTEWORTHY</b> This study demonstrates that host sex, diet, and exercise can each modulate gut bacterial community structure, which may have consequences to host physiology. Our analysis shows selection of novel strains and genera for some members of the <i>Oscillospiraceae</i> and <i>Muribaculaceae</i> by host sex, diet, and activity status. Overall, these findings provide a framework for detecting the next generation of beneficial bacteria targeting obesity and associated metabolic diseases in a sex-specific manner.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1374-1388"},"PeriodicalIF":3.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142287959","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}
Amy S Jordan, Michael J Woods, Jennifer M Cori, Julia K M Chan, Christian L Nicholas, John Semmler, John Trinder
{"title":"Motor control of the palatoglossus and genioglossus during changes in breathing route.","authors":"Amy S Jordan, Michael J Woods, Jennifer M Cori, Julia K M Chan, Christian L Nicholas, John Semmler, John Trinder","doi":"10.1152/japplphysiol.00055.2024","DOIUrl":"10.1152/japplphysiol.00055.2024","url":null,"abstract":"<p><p>High activity of upper airway dilator muscles is thought to be critical in preventing sleep-related upper airway collapse. To date, most of the research regarding upper airway dilator muscles has focused on the genioglossus muscle, which protrudes the tongue and opens the retroglossal airway. However, collapse commonly occurs in the retropalatal region. We, therefore, aimed to examine the motor control of the palatoglossus muscle as well as investigate breathing route-related changes in genioglossus and palatoglossus motor units. Single motor unit recordings of the genioglossus and palatoglossus were made simultaneously in healthy individuals during wakefulness while breathing through the nose with the mouth closed (NMC), nose with mouth open (NMO), or orally (OMO). The palatoglossus was found to have all five motor unit firing patterns that have been observed in other upper airway dilator muscles, but during nasal breathing had a higher proportion of tonically active but inspiratory modulated motor units as compared with the genioglossus (67% vs. 30%). When still breathing nasally but with the mouth open, the units with an expiratory firing pattern in genioglossus, and all firing patterns in palatoglossus, increased their firing rates compared with nasal breathing with the mouth closed [genioglossus (GG): 17.8 ± 4.9 vs. 23.1 ± 4.8 Hz, palatoglossus (PG): 17.0 ± 4.0 vs. 19.3 ± 4.0 Hz]. Finally, oral breathing resulted in dramatic reductions in the number of palatoglossal motor units that were firing (35 units vs. 92 during nasal breathing). Palatoglossal activity may contribute importantly to airway collapsibility and may provide an alternate pathway for preventing sleep-related airway collapse.<b>NEW & NOTEWORTHY</b> The firing patterns of motor units in the palatoglossus have until now not been investigated, and how they and motor units in the genioglossus change with breathing route alteration was not known. This study has shown that the palatoglossus contains motor units with all the firing patterns observed in the genioglossus but in different proportions. Furthermore, breathing route changes alter units with different firing patterns differentially in the two muscles.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1409-1417"},"PeriodicalIF":3.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347219","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}
Joffrey Drigny, Marion Remilly, Corentin Hingrand, Benoît Mauvieux
{"title":"Longitudinal changes in Achilles tendon and triceps surae muscle architecture during a 156-km mountain ultramarathon.","authors":"Joffrey Drigny, Marion Remilly, Corentin Hingrand, Benoît Mauvieux","doi":"10.1152/japplphysiol.00347.2024","DOIUrl":"10.1152/japplphysiol.00347.2024","url":null,"abstract":"<p><p>This study aimed to assess the longitudinal changes in triceps surae muscle-tendon architecture during a mountain ultramarathon. Experienced trail runners [<i>n</i> = 55, 78% men, age: 45.2 (13.5) yr] participated in a 156-km trail run (6,000 m climbing) consisting of six 26-km laps. The resting architectural properties of triceps surae muscle-tendon were measured using ultrasound imaging for Achilles tendon cross-sectional area (AT CSA), medial gastrocnemius muscle pennation angle, thickness, length, and fiber length. Measurements were performed the day before the race (baseline), at 52 km (T1), at 104 km (T2), at 156 km (T3), and 12 h after the race (H12). Among finishers (<i>n</i> = 41), there was a significant biphasic change in AT CSA during the race (<i>P</i> = 0.001). First, a significant decrease in AT CSA occurred between baseline and T1 (<i>P</i> = 0.006), with a greater decrease for participants averaging speed >8 km/h (<i>P</i> = 0.014). Second, there was a significant increase in AT CSA especially between T2 and T3 (<i>P</i> = 0.006) that was correlated with a decrease in average speed (<i>P</i> = 0.001) and alteration of spaciotemporal running parameters (<i>P</i> < 0.05). Changes in muscle-tendon architecture were not significantly different between finishers (<i>n</i> = 41) and nonfinishers (<i>n</i> = 14). In 47 participants (85.5%) who completed the follow-up, AT CSA at H12 was greater compared with baseline (<i>P</i> = 0.010). The main finding is the significant and biphasic modification of the AT CSA during a 156-km mountain ultramarathon with an initial decrease corresponding to mechanical stress followed by a secondary increase suggesting adaptive mechanotransduction persisting after 12 h.<b>NEW & NOTEWORTHY</b> Achilles tendon cross-sectional area (AT CSA) demonstrated significant adaptive modifications during a 156 km mountain ultramarathon in trained athletes. Initially, a decrease in AT CSA, especially at higher running speeds, is consecutive to the biomechanical stress on the plantar flexor muscle-tendon unit (MTU). Subsequently, there is a significant increase in AT CSA persisting up to 12 h after the race, which likely corresponds to an adaptive process to limit the compressive and tensile load on the tendon.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1182-1193"},"PeriodicalIF":3.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141758848","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}
Solomiia Zaremba, Alex J Miller, Erik A Ovrom, Jonathon W Senefeld, Chad C Wiggins, Paolo B Dominelli, Ravindra Ganesh, Ryan T Hurt, Brian J Bartholmai, Brian T Welch, Juan G Ripoll, Michael J Joyner, Andrew H Ramsook
{"title":"Increased luminal area of large conducting airways in patients with COVID-19 and post-acute sequelae of COVID-19: a retrospective case-control study.","authors":"Solomiia Zaremba, Alex J Miller, Erik A Ovrom, Jonathon W Senefeld, Chad C Wiggins, Paolo B Dominelli, Ravindra Ganesh, Ryan T Hurt, Brian J Bartholmai, Brian T Welch, Juan G Ripoll, Michael J Joyner, Andrew H Ramsook","doi":"10.1152/japplphysiol.00573.2024","DOIUrl":"10.1152/japplphysiol.00573.2024","url":null,"abstract":"<p><p>Coronavirus disease 2019 (COVID-19) is associated with enlarged luminal areas of large conducting airways. In 10-30% of patients with acute COVID-19 infection, symptoms persist for more than 4 wk (referred to as post-acute sequelae of COVID 19, or PASC), and it is unknown if airway changes are associated with this persistence. Thus, we aim to investigate whether luminal area of large conducting airways is different between patients with PASC and COVID-19 and healthy controls. In this retrospective case-control study, 75 patients with PASC (48 females) were age-, height-, and sex-matched to 75 patients with COVID-19 and 75 healthy controls. Using three-dimensional digital reconstruction from computed tomography imaging, we measured luminal areas of seven conducting airways, including trachea, right and left main bronchi, bronchus intermediate, right and left upper lobe, and left lower lobe bronchi. Kruskal-Wallis H test was used to compare measurements between the three groups, as appropriate. Airway luminal areas between COVID-19 and PASC groups were not different (all, <i>P</i> > 0.66). There were no group differences in airway luminal area (PASC vs. control) for trachea and right main bronchus. However, in the remaining five airways, airway luminal areas were 12-39% larger among patients with PASC than in controls (all, <i>P</i> < 0.05). Patients diagnosed with COVID-19 and PASC have greater airway luminal area in most large conducting airways compared with healthy controls. No differences in luminal area between patients with COVID-19 and PASC suggest persistence of changes or insufficient time for reversal of changes.<b>NEW & NOTEWORTHY</b> Three-dimensional reconstruction of airways has shown increased luminal area in patients with COVID-19 and post-acute sequelae of COVID-19 when compared with healthy controls. These findings suggest the role of large conducting airways in the pathogenesis of post-acute sequelae of COVID 19.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1168-1174"},"PeriodicalIF":3.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11573277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142287939","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}
Owen T Payne, Michael G Leahy, Jamie F Burr, Jeremy D Road, Donald C McKenzie, A William Sheel
{"title":"No effect of aerobic fitness on exercise-induced diaphragm fatigue in females.","authors":"Owen T Payne, Michael G Leahy, Jamie F Burr, Jeremy D Road, Donald C McKenzie, A William Sheel","doi":"10.1152/japplphysiol.00239.2024","DOIUrl":"10.1152/japplphysiol.00239.2024","url":null,"abstract":"<p><p>We tested the hypothesis that the incidence and magnitude of diaphragm fatigue following high-intensity exercise would be lower in females with a high aerobic capacity (Hi-Fit) compared with healthy females with an average aerobic fitness (Avg-Fit). Participants were assigned to groups based on their peak O<sub>2</sub> uptake (V̇o<sub>2peak</sub>) obtained during cycle exercise: Hi-Fit <i>n</i> = 9, V̇o<sub>2peak</sub> ≥ 56.1 ± 3.4 mL·kg<sup>-1</sup>·min<sup>-1</sup> versus Avg-Fit <i>n</i> = 9, V̇o<sub>2peak</sub> ≤ 35.7 ± 4.9 mL·kg<sup>-1</sup>·min<sup>-1</sup>. On the second day, diaphragm fatigue was assessed before and after constant load exercise test to exhaustion. Magnetic stimulation of the phrenic nerve roots was used to nonvolitionally assess diaphragm fatigue by measurement of transdiaphragmatic twitch pressure (P<sub>di,tw</sub>). Both groups exercised at >90% of V̇o<sub>2peak</sub> for a similar duration (Hi-Fit: 546.1 ± 177.8 vs. Avg-Fit: 559.3 ± 175.0 s, <i>P</i> = 0.9). Diaphragm fatigue was defined as a ≥15% reduction in P<sub>di,tw</sub>, approximately two times greater than the coefficient of variation. The mean group average reduction in P<sub>di,tw</sub> following exercise in the Hi-Fit (17.5%) and Avg-Fit groups (12.2%) was not different between groups (<i>P</i> = 0.2). The Hi-Fit group performed exercise at a higher absolute work rate that elicited significantly greater ventilatory work and inspiratory muscle force output. The Hi-Fit group did not experience greater fatigue compared with the Avg-Fit group, which we attribute to a greater reliance on accessory respiratory muscle recruitment, to training-induced increases in the aerobic capacity of the diaphragm, or a combination of the two. In summary, aerobic fitness is not predictive of exercise-induced diaphragm fatigue in healthy females.<b>NEW & NOTEWORTHY</b> We hypothesized that females with a high aerobic capacity would be resistant to exercise-induced diaphragm fatigue relative to healthy but untrained females. We assessed the pressure generated by the diaphragm following exhaustive exercise by stimulating the phrenic nerves. The magnitude and incidence of fatigue were similar between groups. Despite having higher ventilatory demands during exercise highly trained females were resistant to greater diaphragm fatigue. Aerobic fitness is not predictive of exercise-induced diaphragm fatigue in females.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1145-1157"},"PeriodicalIF":3.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140197","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}
Christina D Bruce, Mathew I B Debenham, Brian H Dalton, Chris J McNeil
{"title":"Acute normobaric hypoxia causes a rightward shift in the torque-frequency relationship but has no effect on postactivation potentiation.","authors":"Christina D Bruce, Mathew I B Debenham, Brian H Dalton, Chris J McNeil","doi":"10.1152/japplphysiol.00378.2024","DOIUrl":"10.1152/japplphysiol.00378.2024","url":null,"abstract":"<p><p>Low fractions of inspired oxygen ([Formula: see text]; i.e., hypoxia) affect aspects of skeletal muscle contractility in humans, but it remains unclear if postactivation potentiation (PAP) and the torque-frequency (T-F) relationship are altered. We investigated the effects of 2 (H2) and 4 (H4) h of normobaric hypoxia ([Formula: see text] = 0.11 ± 0.47) on the magnitude of PAP of the knee extensors and the T-F relationship of the dorsiflexors in 13 and 12 healthy participants, respectively. To assess PAP, a resting twitch was evoked via femoral nerve stimulation before and 2-300 s after a 10-s maximal voluntary contraction (MVC). A T-F relationship was obtained by stimulating the common fibular nerve with a single pulse and 1-s trains between 5 and 100 Hz. During hypoxia, peripheral oxygen saturation decreased by ∼18% from 98.0 ± 0.8% at baseline (<i>P</i> < 0.001). MVC force and voluntary activation (VA) of the knee extensors were lower than baseline throughout hypoxia (e.g., ∼8% and ∼5%, respectively, at H2; <i>P</i> ≤ 0.027); however, the magnitude of PAP was not altered by hypoxia (<i>P</i> ≥ 0.711). Surprisingly, PAP did increase with time across the control day (<i>P</i> ≤ 0.012). MVC torque and VA of the dorsiflexors were unaffected by hypoxia (<i>P</i> ≥ 0.127), but the estimated frequency required to evoke 50% of 100 Hz torque increased by ∼1.2 Hz at H2 (<i>P</i> ≤ 0.021). These results imply that 2 h of normobaric hypoxia were sufficient to <i>1</i>) impair neural drive to the knee extensors but not the mechanism(s) responsible for PAP and <i>2</i>) lead to a rightward shift of the T-F relationship for the dorsiflexors.<b>NEW & NOTEWORTHY</b> Postactivation potentiation of the knee extensors was unaffected by 4 h of normobaric hypoxia exposure but may be confounded by hypoxia-related impairments to the conditioning contraction. In the dorsiflexors, contractile rates increased in hypoxia, which led to a rightward shift of the torque-frequency relationship, such that a higher frequency was required to obtain 50% of maximal torque. These results expand our understanding of the acute effects of hypoxia on skeletal muscle function.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1389-1396"},"PeriodicalIF":3.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142287937","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}
Matthew C Babcock, Omar B El-Kurd, James R Bagley, Braxton A Linder, Nina L Stute, Soolim Jeong, Joseph D Vondrasek, Joseph C Watso, Austin T Robinson, Gregory J Grosicki
{"title":"Acute cardiovascular responses to the 100-mi Western States Endurance Run.","authors":"Matthew C Babcock, Omar B El-Kurd, James R Bagley, Braxton A Linder, Nina L Stute, Soolim Jeong, Joseph D Vondrasek, Joseph C Watso, Austin T Robinson, Gregory J Grosicki","doi":"10.1152/japplphysiol.00412.2024","DOIUrl":"10.1152/japplphysiol.00412.2024","url":null,"abstract":"<p><p>Ultramarathon participation is growing in popularity and exposes runners to unique stressors including extreme temperatures, high altitude, and exceedingly long exercise duration. However, the acute effects of ultramarathon participation on the cardiovascular system are not well understood. To determine the acute effects of trail ultramarathon participation on central artery stiffness and hemodynamics, 41 participants (9 F, 32 M) participating in the 2023 Western States Endurance Run underwent measures of carotid-femoral pulse wave velocity (cf-PWV) and pulse wave analysis pre- and <1 h post-race. Subendocardial viability ratio (SEVR) was calculated from central blood pressure (BP) waveforms. Serum was analyzed for creatine kinase (CK) activity as a measure of muscle damage. Normally distributed data are presented as means ± standard deviation (SD), and nonnormally distributed data are presented as median (interquartile range). Runners were middle-aged and generally lean [age = 44 ± 9 yr, body mass index (BMI) = 22.7 ± 1.8 kg·m<sup>-2</sup>]. There was no difference in cf-PWV from pre- to post-race (pre = 6.4 ± 1.0, post = 6.2 ± 0.85 m/s, <i>P</i> = 0.104), a finding that persisted after adjusting for mean arterial pressure (<i>P</i> = 0.563). Systolic and diastolic BPs were lower post-race (pre = 129/77 ± 9/7, post = 122/74 ± 10/8 mmHg, <i>P</i> < 0.001). Augmentation index (AIx; pre = 17.3 ± 12.2, post = 6.0 ± 13.7%, <i>P</i> < 0.001), AIx normalized to a heart rate of 75 beats/min (<i>P</i> = 0.043), reflection magnitude (pre = 55.5(49.0-60.8), post = 45.5(41.8-48.8)%, <i>P</i> < 0.001), and SEVR (pre = 173.0(158.0-190.0), post = 127.5(116.5-145.8)%, <i>P</i> < 0.001) were reduced post-race. CK increased markedly from pre- to post-race (pre = 111(85-162), post = 11,973(5,049-17,954) U/L, <i>P</i> < 0.001). Completing a 161-km trail ultramarathon does not affect central arterial stiffness and acutely reduces BP despite eliciting profound muscle damage. However, the reduced post-race SEVR suggests a short-term mismatch between myocardial work and coronary artery perfusion.<b>NEW AND NOTEWORTHY</b> Ultramarathon participation is growing dramatically. However, the acute cardiovascular effects of completing a 161-km trail ultramarathon remain unknown. We examined the acute effects of completing the 2023 Western States Endurance Run on arterial stiffness and central hemodynamics in a relatively large sample of males and females. We observed dramatic postexercise hypotension, reductions in reflected wave amplitude and reduced subendocardial viability ratio post-race. These findings suggest that ultramarathon participation has few negative effects on cardiovascular health.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1257-1266"},"PeriodicalIF":3.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142287936","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}