Journal of applied physiology最新文献

{"title":"Prophylactic caffeine mitigates systemic hypercapnia and headache during graded carbon dioxide exposure in healthy males and females: a randomized crossover trial.","authors":"Benjamin J Ryan, Thomas A Mayer, Billie K Alba, Karleigh E Bradbury, Shaun C Brazelton, Nisha Charkoudian, K Riley Connor, Benjamin A Fry, Gabrielle E W Giersch, Rachel A Gioscia-Ryan, Andrew M Greenfield, Harris R Lieberman, Afton D Seeley, John H Sellers, Joseph D Shevchik, Jesse A Stein, Erik R Swenson, Roy M Salgado","doi":"10.1152/japplphysiol.01024.2024","DOIUrl":"10.1152/japplphysiol.01024.2024","url":null,"abstract":"<p><p>Exposure to elevated inspired carbon dioxide (CO₂) levels, an environmental threat in several occupational settings, is known to induce systemic hypercapnia and provoke headache. However, the impact of CO₂ exposure dose on headache severity has not been determined, and countermeasures to mitigate systemic hypercapnia and headache during CO₂ exposure are lacking. In this study, we first characterized respiratory responses and headache with graded CO₂ exposure (sequential 12-min stages of 0%, 2%, 4%, 6%, and 8% inspired CO₂, all with 21% oxygen) during seated rest in 24 healthy males and females. As expected, graded CO₂ exposure resulted in stepwise increases (41 ± 3, 43 ± 2, 46 ± 2, 53 ± 2, 65 ± 1 mmHg; <i>P</i> < 0.001) in end-tidal CO₂ across the spectrum from normocapnia to severe hypercapnia. Headache increased (<i>P</i> < 0.05) beginning at 4% inspired CO₂ (1 ± 2, 2 ± 3, 8 ± 8, 16 ± 13, 32 ± 20 mm on a 100-mm visual analog scale). Participants then completed the same graded CO₂ exposure 1 h following either caffeine (400 mg) or placebo supplementation in a randomized, double-blind, crossover manner (<i>n</i> = 23). Caffeine increased ventilation and lowered end-tidal CO₂ at inspired CO₂ levels between 0% and 6% (<i>P</i> < 0.05), corresponding with a leftward shift in the end-tidal CO₂-ventilation response curve with unchanged slope. Caffeine substantially reduced headache during graded CO₂ exposure, an effect that was most pronounced at 8% inspired CO₂ (placebo: 25 ± 15 mm, caffeine: 13 ± 12 mm; <i>P</i> < 0.05). Our novel findings establish prophylactic caffeine supplementation as a translational countermeasure to mitigate systemic hypercapnia and headache during CO₂ exposure.<b>NEW & NOTEWORTHY</b> In this study, we first characterized systemic hypercapnia and headache severity during graded CO₂ exposures (sequential 12-min stages of 0%, 2%, 4%, 6%, and 8% inspired CO₂). Using a randomized, double-blind, crossover trial, we then showed that prophylactic treatment with 400 mg caffeine mitigates systemic hypercapnia and headache during graded CO₂ exposure. Overall, these novel findings establish caffeine as the first evidence-based countermeasure to mitigate adverse effects associated with CO₂ exposure.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"881-890"},"PeriodicalIF":3.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523364","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":"Diaphragm blood flow: new avenues for human translation.","authors":"Jordan D Bird, Megan L Lance, Damien Bachasson, Paolo B Dominelli, Glen E Foster","doi":"10.1152/japplphysiol.00669.2024","DOIUrl":"10.1152/japplphysiol.00669.2024","url":null,"abstract":"<p><p>The rhythmic contraction of the diaphragm facilitates continuous pulmonary ventilation essential for life. Adequate blood flow to the diaphragm is critical to continuously support contractile function, as an imbalance in nutritive supply and demand can lead to diaphragm insufficiency, patient morbidity, and mortality. Given oxygen supply to the diaphragm is key to its function, it is no surprise that more than 200 animal studies have investigated diaphragm blood flow ([Formula: see text]) regulation over the past century. This work has advanced our understanding of the diaphragm's circulatory control (i.e., regional blood flow heterogeneity and mechanical impediment) and response to a variety of conditions, including eupnea, exercise, hypoxia, hypercapnia, hemorrhage, mechanical ventilation, and pharmacological interventions. However, due to the relative inaccessibility of the diaphragm, few studies have been conducted in humans since [Formula: see text] measurements have historically required highly invasive and technically challenging techniques that are not conducive to routine use. Thus, our current understanding of [Formula: see text] is informed almost exclusively by animal work with conflicting findings, and its translation to humans is hindered by species-dependent variability in diaphragmatic structure and function. Novel approaches have been developed to quantify respiratory muscle blood flow in humans using minimally invasive techniques. More recently, contrast-enhanced ultrasound (CEUS) is a promising approach for quantifying [Formula: see text] in humans, independent from other respiratory muscles. Using novel approaches to quantify [Formula: see text] in humans, future research can aim to advance our understanding of [Formula: see text] in humans in health and disease, including exercise, sex-based comparisons, and critical care.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"909-925"},"PeriodicalIF":3.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572991","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":"Sex differences in the physiological and perceptual responses to face masks during exercise.","authors":"O N Ferguson, M R Flynn, R A Mitchell, A S Hind, J I Arnold, S S Dhillon, P B Dominelli, Y Molgat-Seon, J A Guenette","doi":"10.1152/japplphysiol.00679.2024","DOIUrl":"10.1152/japplphysiol.00679.2024","url":null,"abstract":"<p><p>Despite consistent evidence that face masks (FMs) increase dyspnea during exercise, few studies have examined the sex differences in the physiological and perceptual responses to FMs. In a randomized, crossover design, 32 healthy individuals (16 females; 23 ± 3 yr) completed incremental cycling tests on two visits with either no mask or a surgical FM. Dyspnea intensity and unpleasantness were assessed using the 0-10 category-ratio Borg scale. Diaphragmatic electromyography, esophageal pressure (P_eso), and transdiaphragmatic pressure (P_di) were measured using a nasogastric catheter to estimate neural inspiratory drive and respiratory muscle effort. Surface electromyography (EMG) was measured on the sternocleidomastoid and scalene muscles. FMs resulted in a steeper increase in dyspnea unpleasantness in males compared with females across the 0%-100% work rate (estimate = 1.5 CR10, <i>P</i> = 0.0048), with no significant difference in the effect of the FM on dyspnea intensity between sexes (<i>P</i> > 0.05). Males had a greater increase in P_eso and P_di with FMs compared with females across work rate (-3.8 cmH₂O, <i>P</i> = 0.0088; -4.7 cmH₂O, <i>P</i> = 0.011, respectively) and a greater increase in sternocleidomastoid activation from 40%-60% work rate (WR) (all <i>P</i> < 0.05). In addition, moisture accumulation pre- versus postexercise (<i>P</i> = 0.01) was significantly greater in males compared with females. FMs resulted in a similar absolute reduction in exercise time in both sexes although it was only statistically significant in females (<i>P</i> = 0.006). This study highlights that males likely experience greater dyspnea unpleasantness with FMs due to higher flows and ventilations, which increase mask resistance and, combined with greater moisture accumulation, elevate respiratory muscle effort and accessory muscle activation. Nonetheless, the absolute impact on exercise duration appears similar between sexes.<b>NEW & NOTEWORTHY</b> During the coronavirus disease 2019 pandemic, numerous studies evaluated the effects of face masks on the physiological and perceptual responses to exercise. However, the symptoms of breathlessness and associated physiological mechanisms were largely neglected. In addition, our understanding of whether face masks affected males and females differently was particularly limited. We found that sex-specific physiological responses can guide exercise and face mask strategies to improve comfort and performance for individuals engaging in prolonged, intense workouts.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"926-938"},"PeriodicalIF":3.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515705","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":"Eight weeks of eccentric training at long-muscle length increases fascicle length independently of adaptations in passive mechanical properties.","authors":"Baptiste Bizet, Antoine Nordez, Tristan Tallio, Lilian Lacourpaille, Thomas Cattagni, Julian Colard, Yohan Betus, Sylvain Dorel, Aurélie Sarcher, Olivier Seynnes, Ricardo J Andrade","doi":"10.1152/japplphysiol.00859.2024","DOIUrl":"10.1152/japplphysiol.00859.2024","url":null,"abstract":"<p><p>Eccentric exercise training is believed to induce an increase in muscle fascicle length. However, the mechanisms underlying this adaptation are not fully understood. This study aimed to determine if an increase in gastrocnemius medialis fascicle length following an 8-wk eccentric training is linked to changes in muscle tissue and joint mechanical properties. Thirty-three physically active young adults were assigned to one of the two training protocols targeting the plantar flexors: eccentric exercise at <i>1</i>) long-muscle length or <i>2</i>) short-muscle length. Fascicle length and muscle shear modulus of the gastrocnemius medialis were assessed using ultrasound imaging during passive ankle rotations, alongside measurements of passive ankle torque. A total of 27 participants successfully completed the training program and data processing stage (long-muscle length, <i>n</i> = 15; short-muscle length, <i>n</i> = 12). Maximal voluntary isometric torque increased significantly following the training programs (9.5%), with no differences between training groups. An increase in fascicle length (mean 8.5%) was observed in the long-muscle length group, from 39.5 ± 0.7° to 36.8 ± 0.8° in plantar flexion, but not in the short-muscle length group. Notably, this macrostructural adaptation was detected only at muscle lengths shorter than the slack length (i.e., absence of any muscle passive tension). The eccentric training did not alter the muscle shear modulus or slack length. Collectively, these findings suggest that fascicle length adaptations in response to eccentric training were unrelated to changes in passive muscle-tendon mechanical properties. Consequently, the increase in fascicle length may be attributed to an increase in sarcomere length and/or an addition of sarcomeres in series.<b>NEW & NOTEWORTHY</b> We demonstrate that an 8-wk eccentric training program significantly increases gastrocnemius medialis fascicle length in humans, independent of any adaptions in passive muscle-tendon mechanical properties. Fascicle length adaptions were specific to the group that trained at long-muscle lengths, highlighting the importance of the muscle-tendon length range during eccentric exercise programs. This factor may be crucial for fine-tuning structural adaptations at the fascicle level, likely through the addition of sarcomeres in series.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"939-949"},"PeriodicalIF":3.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573036","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":"Cerebrovascular responses to muscle metaboreflex activation in patients living with heart failure with reduced ejection fraction.","authors":"Thomas J Jurrissen, Adam M S Luchkanych, Natasha G Boyes, Rory A Marshall, M Rafique Khan, Alexander Zhai, Haissam Haddad, Darcy D Marciniuk, Corey R Tomczak, T Dylan Olver","doi":"10.1152/japplphysiol.00834.2024","DOIUrl":"10.1152/japplphysiol.00834.2024","url":null,"abstract":"<p><p>Impaired cerebrovascular control in patients with heart failure with reduced ejection fraction (HFrEF) has been attributed to cardiac impairment and exaggerated sympathetic-mediated cerebral vasoconstriction. The goal of this study was to examine the effect of muscle metaboreflex activation (MMA) on cerebrovascular hemodynamics in patients with HFrEF under conditions of preserved cardiac output. It was hypothesized that reductions in the index of cerebral blood flow and cerebrovascular conductance (CVCi) during MMA would be exaggerated in HFrEF and independent of reduced cardiac output. Middle cerebral blood velocity (MCA_Vmean; transcranial Doppler), blood pressure, cardiac output (Finometer), and end-tidal CO₂ were examined at rest, during isometric handgrip, and during muscle MMA (postexercise circulatory occlusion) in 18 patients with HFrEF and 21 healthy, sex-, and age-matched controls. To minimize differences in β-adrenergic control, patients with HFrEF withdrew from β-blockade medications before the study. Cardiac index and blood pressure were not significantly different between groups under any condition. The MCA_Vmean was lower at rest and during exercise in HFrEF. The CVCi (MCA_Vmean/mean arterial pressure) and MCA_Vmean decreased during MMA in the control group. In contrast, the CVCi remained unchanged and MCA_Vmean increased during MMA in the HFrEF group. Despite similar systemic hemodynamics, patients with HFrEF display lower MCA_Vmean at rest and an increase in MCA_Vmean during MMA. These novel findings implicate aspects other than reduced cardiac output or exaggerated sympathetic constriction as underlying causes of altered cerebrovascular regulation in HFrEF.<b>NEW & NOTEWORTHY</b> Compared with controls, patients with heart failure with reduced ejection fraction (HFrEF) displayed reduced indices of cerebral perfusion at rest and increases in perfusion in response to postexercise circulatory occlusion (PECO, method to isolate muscle metaboreflex activation). This occurred despite similar cardiac output and blood pressure values between groups. Thus, lower resting indices of cerebral perfusion and increased perfusion during sympathoexcitation in HFrEF may occur independently from differences in systemic hemodynamics.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"891-898"},"PeriodicalIF":3.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542044","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":"Short bouts of hypoxia improve insulin sensitivity in adults with type 2 diabetes.","authors":"Jiahui Zhao, Sahar D Massoudian, Sten Stray-Gundersen, Frank Wojan, Sophie Lalande","doi":"10.1152/japplphysiol.00932.2024","DOIUrl":"10.1152/japplphysiol.00932.2024","url":null,"abstract":"<p><p>Hypoxia stimulates glucose uptake independently from the action of insulin. The purpose of this study was to determine the effect of intermittent hypoxia, consisting of alternating short bouts of breathing hypoxic and room air, on glucose concentration, insulin concentration, and insulin sensitivity during an oral glucose tolerance test in adults with type 2 diabetes and adults with normal glycemic control. Nine adults with type 2 diabetes (2 women, HbA1c: 7.3 ± 1.5%, age: 52 ± 13 yr) and nine adults with normal glycemic control (4 women, HbA1c: 5.4 ± 0.1%, age: 24 ± 4 yr) performed a 2-h oral glucose tolerance test on two separate visits to the laboratory. Following ingestion of the glucose drink, participants were exposed to either an intermittent hypoxia protocol, consisting of eight 4-min hypoxic cycles at a targeted oxygen saturation of 80% interspersed with breathing room air to resaturation, or a sham protocol consisting of eight 4-min normoxic cycles interspersed with breathing room air. Intermittent hypoxia did not attenuate the increase in glucose concentration but attenuated the increase in insulin concentration in response to an oral glucose tolerance test in comparison with the sham protocol in adults with type 2 diabetes. Insulin sensitivity was greater during intermittent hypoxia in comparison with the sham protocol in adults with type 2 diabetes (0.043 ± 0.036 vs. 0.032 ± 0.046 μmol/kg/min/pmol, <i>P</i> = 0.01), but did not change in the control group (0.122 ± 0.015 vs. 0.128 ± 0.008 μmol/kg/min/pmol, <i>P</i> = 0.12). In conclusion, intermittent hypoxia improved insulin sensitivity in adults with type 2 diabetes.<b>NEW & NOTEWORTHY</b> The aim of this study was to determine the effect of short bouts of hypoxia, which stimulates glucose uptake, on glucose concentration, insulin concentration, and insulin sensitivity during an oral glucose tolerance test in adults with type 2 diabetes and adults with normal glycemic control. Intermittent hypoxia acutely improved insulin sensitivity in adults with type 2 diabetes.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"873-880"},"PeriodicalIF":3.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515809","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":"Sexually dimorphic mechanisms of H₂O₂-mediated dilation in porcine coronary arterioles with ischemia and endurance exercise training.","authors":"Kalen Johnson, Jeff F Bray, Cristine L Heaps","doi":"10.1152/japplphysiol.00761.2024","DOIUrl":"10.1152/japplphysiol.00761.2024","url":null,"abstract":"<p><p>We determined the impact of sex on H₂O₂-mediated dilation in coronary arterioles and the contribution of K⁺ channels after exercise training in ischemic heart disease. We hypothesized that arterioles from male and female swine would similarly display impaired H₂O₂-induced dilation after chronic occlusion that would be corrected by exercise training. Yucatan miniswine were surgically instrumented with an ameroid constrictor around the proximal left circumflex artery, gradually inducing occlusion and a collateral-dependent myocardium. Arterioles from the left anterior descending artery myocardial region served as nonoccluded controls. Eight weeks postoperatively, swine of each sex were separated into sedentary and exercise-trained (progressive treadmill regimen; 5 days/wk for 14 wk) groups. Collateral-dependent arterioles of sedentary female pigs displayed impaired sensitivity to H₂O₂ that was reversed with exercise training. In contrast, male pigs exhibited enhanced sensitivity to H₂O₂ in collateral-dependent versus nonoccluded arterioles in both sedentary and exercise-trained groups. Large-conductance, calcium-dependent K⁺ (BKCa) and 4-aminopyridine (AP)-sensitive voltage-gated K⁺ (Kv) channels contributed to H₂O₂-mediated dilation in nonoccluded and collateral-dependent arterioles of exercise-trained females, but not in arterioles of sedentary female or sedentary or exercise-trained male swine. BKCa channel, protein kinase A (PKA), and protein kinase G (PKG) protein levels were not significantly different between groups, nor were kinase enzymatic activities. Taken together, our studies suggest that in female swine, exercise training stimulates the coupling of H₂O₂ signaling with BKCa and 4-AP-sensitive Kv channels, compensating for impaired dilation in collateral-dependent arterioles. Interestingly, coronary arterioles from neither sedentary female or male swine, regardless of training status, depended upon BKCa or 4-AP-sensitive Kv channels for H₂O₂-mediated dilation.<b>NEW & NOTEWORTHY</b> The current studies reveal sexually dimorphic adaptations to H₂O₂-mediated dilation, and unique contributions of K⁺ channels, in coronary arterioles from swine subjected to chronic ischemia and exercise training; findings important for development of therapeutic strategies. In female swine, chronic ischemia attenuates dilation, which is reversed by exercise training via BKCa and Kv channel stimulation. In male swine, ischemia enhances dilation to H₂O₂, which is further augmented by exercise training and independent of BKCa and Kv channels.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"950-963"},"PeriodicalIF":3.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584862","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":"Leg stiffness adjustment during hopping by dynamic interaction between the muscle and tendon of the medial gastrocnemius.","authors":"Kazuki Kuriyama, Daisuke Takeshita","doi":"10.1152/japplphysiol.00375.2024","DOIUrl":"10.1152/japplphysiol.00375.2024","url":null,"abstract":"<p><p>The biomechanics underlying bouncing exercises are characterized by the spring-like behavior of the human leg. This study investigated a specific form of hopping-performed with an extended knee and minimal ground contact duration-to examine how muscle dynamics contribute to leg stiffness adjustment. This constrained hopping pattern allows us to isolate the role of ankle joint, especially plantar flexor muscle-tendon complex (MTC). To quantitatively analyze changes in the MTC of the medial gastrocnemius (MG) muscle, we utilized an MTC model comprising an active spring and a passive spring connected in series, representing a contractile component (CC) and series elastic component (SEC), respectively. We hypothesized that an increase in CC stiffness would coincide with the increase in leg stiffness, thereby enabling hopping at higher frequencies. Joints and MG fascicle dynamics were collected across different hop frequencies. The results showed that the stiffness of the MTC increased with hop frequency and exhibited a strong correlation with the leg stiffness. In addition, with increasing frequency, the fascicle contractions shifted from isometric to concentric. Consequently, a negative CC stiffness was observed, thereby increasing the overall MTC stiffness. Although this result appears to diverge from our initial hypothesis, the effect of negative CC stiffness on MTC stiffness can be understood, from the perspective of two springs in series, as an extension of the very high stiffness effect. This quantitative understanding of the dynamic interaction between the fascicle and tendon provides deeper insight into the adjustment mechanisms underlying bouncing gaits.<b>NEW & NOTEWORTHY</b> The mechanistic understanding of how humans adjust leg stiffness in bouncing exercises remains unclear. An MTC model comprising two springs, contractile and series elastic components, was used to analyze the medial gastrocnemius muscle dynamics during hopping with different hop frequencies. The contractile component showed negative stiffness at high hop frequency due to shortening against increasing load, achieving high MTC stiffness and leg stiffness required for high-frequency hopping.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"899-908"},"PeriodicalIF":3.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542048","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":"Whole genome transcriptomic profiling reveals distinct sex-specific responses to heat stroke.","authors":"Abderrezak Bouchama, Maria Gomez, Mashan L Abdullah, Saeed Al Mahri, Shuja Shafi Malik, Saber Yezli, Sameer Mohammad, Cynthia Lehe, Bisher Abuyassin, Robert Hoehndorf","doi":"10.1152/japplphysiol.00001.2025","DOIUrl":"10.1152/japplphysiol.00001.2025","url":null,"abstract":"<p><p>Heat-related mortality remains health challenges exacerbated by climate change, with sex-based differences in outcomes, yet underlying mechanisms remain poorly understood. This study examined transcriptomic responses to heat exposure in peripheral blood mononuclear cells from 19 patients with heat stroke (HS; 8 males, mean age 64.8 ± 6.6 yr; 11 females, mean age 49.7 ± 11 yr) and 19 controls (11 males, mean age 48.9 ± 9.6 yr; 8 females, mean age 44.9 ± 11.8 yr). At admission, gene expression revealed upregulation of heat shock protein genes, and pathway analysis demonstrated activation of heat shock and unfolded protein responses across both sexes consistent with proteotoxic stress. However, distinct metabolic, oxidative stress, cell cycle control, and immune responses were observed within each sex. Females displayed inhibition of protein synthesis, oxidative phosphorylation, and metabolic pathways, including glucose metabolism, indicative of a hypometabolic state. Males maintained metabolic activity precooling and enhanced adenosine triphosphate production postcooling. Females activated nuclear factor erythroid 2-related factor 2 (NRF2)-mediated oxidative stress responses and inhibited DNA replication and mitosis, potentially mitigating genomic instability, whereas these pathways showed limited regulation in males. Females promoted innate immunity via interleukin (IL)-6, inflammasome, and triggering receptor expressed on myeloid cells 1 (TREM1) signaling, whereas males showed suppression of both innate and adaptive immunity, including IL-12, Th1, and T-cell receptor pathways. Upstream analysis identified over 100 transcription factors in both sexes. Males primarily relied on transcriptional mechanisms, whereas females also exhibited translational regulation via La ribonucleoprotein 1 (LARP1), fragile X messenger ribonucleoprotein 1 (FMR1), insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1), and eukaryotic translation initiation factor 6 (EIF6). These findings suggest distinct, sex-specific molecular adaptations to heat stroke, underscoring the need for targeted therapeutic strategies to mitigate heat-induced morbidity and mortality.<b>NEW & NOTEWORTHY</b> Heat-related mortality continues to rise with climate change. Our transcriptomic analysis reveals distinct sex-specific metabolic strategies to heat stroke: females enter a hypometabolic state, an evolutionary adaptation that conserves energy, whereas males sustain metabolic activity. Transcription factors and a subset of translation regulators in females modulate proteostasis and bioenergetics, driving these sex-specific pathways. These novel findings highlight the critical need to consider sex-specific differences in heat-related illnesses and inform carefully targeted interventions to improve patient outcomes.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"964-978"},"PeriodicalIF":3.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604951","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":"Home-based heat therapy lowers blood pressure and improves endothelial function in older adults.","authors":"Ysabella I Ruiz-Pick, Heidi L Cope, Rauchelle E Richey, Amy M Moore, Tyson C Garfield, Albert H Olivencia-Yurvati, Steven A Romero","doi":"10.1152/japplphysiol.00977.2024","DOIUrl":"10.1152/japplphysiol.00977.2024","url":null,"abstract":"<p><p>Advancing age is associated with vascular dysfunction and hypertension, both of which increase cardiovascular event risk. Heat therapy has emerged as a novel intervention to improve cardiovascular health in various populations. Therefore, we tested the hypothesis that home-based lower body heat therapy would reduce blood pressure and improve endothelium-dependent vasodilation in older adults. Ambulatory blood pressure monitoring was performed in 19 older adults (67 ± 7 yr) before and after 8 wk of a sham intervention or heat therapy. Endothelium-dependent vasodilation of the superficial femoral artery was assessed via flow-mediated dilation. Participants were provided with a pair of tube-lined pants connected to a portable water circulator to perform the home-based sessions. Water temperature was set to 31°C for sham and 51°C for heat therapy, resulting in target skin temperatures of ∼33°C and ∼40°C, respectively. Participants were instructed to wear the pants 4 days/wk for 60 min each session. Adherence was 100% for both groups. Heat therapy reduced ambulatory daytime systolic blood pressure by Δ -5 ± 8 mmHg, but was unchanged for the sham group (Δ 1 ± 6 mmHg; <i>P</i> = 0.04). Likewise, heat therapy increased flow-mediated dilation (<i>P</i> = 0.02), whereas there was no change across time for the sham group (<i>P</i> = 0.5). These results combined with a strong adherence rate suggest that home-based lower body heat therapy could be an alternative nonpharmacological intervention to reduce blood pressure and improve vascular function, ultimately reducing long-term cardiovascular event risk in older adults.<b>NEW & NOTEWORTHY</b> Advancing age is associated with vascular dysfunction and hypertension, both of which increase cardiovascular event risk. This study determined that 8 wk of home-based lower body heat therapy reduced ambulatory daytime systolic blood pressure and increased flow-mediated dilation of the superficial femoral artery, outcomes not observed in the sham group. These improvements, coupled with 100% adherence among participants, suggest that home-based heat therapy is a pragmatic and effective strategy for improving cardiovascular health in older adults.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"979-987"},"PeriodicalIF":3.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585846","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}