K Austin Davis, Nasrul A Bhuiyan, Benjamin J McIntyre, Viet Q Dinh, Caroline A Rickards
{"title":"Induced blood flow oscillations at 0.1 Hz protects oxygenation of severely ischemic tissue in humans.","authors":"K Austin Davis, Nasrul A Bhuiyan, Benjamin J McIntyre, Viet Q Dinh, Caroline A Rickards","doi":"10.1152/japplphysiol.00438.2024","DOIUrl":"10.1152/japplphysiol.00438.2024","url":null,"abstract":"<p><p>Generating 10-s (∼0.1 Hz) fluctuations or \"oscillations\" in arterial pressure and blood flow blunts reductions in cerebral tissue oxygenation in response to 15%-20% reductions in cerebral blood flow. To examine the effect of 0.1 Hz hemodynamic oscillations on tissue oxygenation during severe ischemia, we developed a partial limb ischemia protocol targeting a 70%-80% reduction in blood flow. We hypothesized that 0.1 Hz hemodynamic oscillations would attenuate reductions in tissue oxygenation during severe ischemia. Thirteen healthy humans (6 M and 7 F; 27.3 ± 4.2 yr) completed two experimental protocols separated by ≥48 h. In both conditions, an upper arm cuff was used to decrease brachial artery (BA) blood velocity by ∼70%-80% from baseline. In the oscillation condition (0.1 Hz), 0.1 Hz hemodynamic oscillations were induced by intermittently inflating and deflating bilateral thigh cuffs every 5 s during forearm ischemia. In the control condition (0 Hz), the thigh cuffs were inactive. BA blood flow, forearm tissue oxygenation (SmO<sub>2</sub>), and arterial pressure were measured continuously. The initial reduction in BA blood velocity was tightly matched between protocols (0 Hz: -76.9 ± 7.9% vs. 0.1 Hz: -75.5 ± 7.4%, <i>P</i> = 0.49). Although 0.1 Hz oscillations during forearm ischemia had no effect on the reduction in BA velocity (0 Hz: -73.0 ± 9.9% vs. 0.1 Hz: -73.3 ± 8.2%, <i>P</i> = 0.91), the reduction in SmO<sub>2</sub> was attenuated (0 Hz: -35.7 ± 8.6% vs. 0.1 Hz: -27.2 ± 8.9%, <i>P</i> = 0.01). These data provide further evidence for the use of 0.1 Hz hemodynamic oscillations as a potential therapeutic intervention for conditions associated with severe tissue ischemia (e.g., hemorrhage and stroke).<b>NEW & NOTEWORTHY</b> We investigated the effects of induced 10-s (0.1 Hz) oscillations in blood flow on forearm tissue oxygenation during severe ischemia. Intermittent inflation of bilateral thigh cuffs was used as a clinically applicable method to drive blood flow oscillations. In support of our hypothesis, 0.1 Hz oscillations in blood flow blunted reductions in forearm tissue oxygenation. These results further support the potential use of oscillatory hemodynamics as a therapeutic intervention for ischemic conditions.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1243-1256"},"PeriodicalIF":3.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142287940","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}
Kari C Goodwin, Gabrielle E W Giersch, Timothy A Murray, David W DeGroot, Nisha Charkoudian
{"title":"Sex differences in biomarkers of end-organ damage following exertional heat stroke in humans.","authors":"Kari C Goodwin, Gabrielle E W Giersch, Timothy A Murray, David W DeGroot, Nisha Charkoudian","doi":"10.1152/japplphysiol.00463.2024","DOIUrl":"10.1152/japplphysiol.00463.2024","url":null,"abstract":"<p><p>Women are participating in military and athletic activities in the heat in increasing numbers, but potential sex differences in sequelae from exertional heat illness remain poorly understood. We tested the hypothesis that women suffering from exertional heat stroke (EHS) would have similar severity of organ damage biomarkers compared with men, as measured in a hospital setting. We studied women and men presenting with EHS to the emergency department at Fort Moore, GA. We measured creatinine (CR), creatine kinase (CK), alanine-transaminase (ALT), aspartate aminotransferase (AST), and estimated glomerular filtration rate (eGFR). Core temperature was also assessed by medical personnel. Biomarker data were obtained for 62 EHS cases (11 women). Men were significantly taller, and heavier, and had larger body mass index (BMI) and body surface area (<i>P</i> < 0.05 for all). The highest recorded body core temperature was not different between groups [women: 41.11°C (40.06, 41.67); men: 41.11°C (40.28, 41.72), <i>P</i> = 0.57]. Women had significantly lower peak CR [women: 1.39 (1.2, 1.48) m·dL<sup>-1</sup>; men: 1.75 (1.53, 2.16) mg·dL<sup>-1</sup>, <i>P</i> < 0.01] and peak CK [women: 584 (268, 2,412) U·L<sup>-1</sup>; men: 2,183 (724, 5,856) U·L<sup>-1</sup>, <i>P</i> = 0.02]. Peak ALT and AST were not different between groups; during recovery time points, ALT and AST were either similar or lower in women. Women spent approximately half as much time in the hospital following admittance compared with men. Our findings suggest that women may be less susceptible to organ injury resulting from EHS. Further research is necessary to understand the pathophysiology underlying these differences and how biomarkers of end-organ damage severity can differ between women and men following EHS.<b>NEW & NOTEWORTHY</b> We studied otherwise healthy women and men after exertional heat stroke in a military training environment. Peak values for biomarkers of kidney and muscle damage were lower in women compared with men despite similar (highest recorded) body core temperatures. During recovery, organ damage markers were similar or lower in women. These sex differences may indicate differences in the pathophysiology of responses, but more work is needed to clarify specific mechanisms.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1434-1445"},"PeriodicalIF":3.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11573266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142287957","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}
Maxime Boidin, Catherine-Alexandra Grégoire, Christine Gagnon, Nathalie Thorin-Trescases, Eric Thorin, Anil Nigam, Martin Juneau, Arthur Guillaume, Jonathan Tremblay, Mathieu Gayda, Louis Bherer
{"title":"Effects of variation in exercise training load on cognitive performances and neurotrophic biomarkers in patients with coronary artery disease.","authors":"Maxime Boidin, Catherine-Alexandra Grégoire, Christine Gagnon, Nathalie Thorin-Trescases, Eric Thorin, Anil Nigam, Martin Juneau, Arthur Guillaume, Jonathan Tremblay, Mathieu Gayda, Louis Bherer","doi":"10.1152/japplphysiol.00636.2023","DOIUrl":"10.1152/japplphysiol.00636.2023","url":null,"abstract":"<p><p>This study compared the effects of linear (LP) and nonlinear (NLP) training periodization on cognitive functions, neurotrophic biomarkers [plasma brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1)], and cathepsin-B in patients with coronary artery disease (CAD). Forty-four patients with CAD reported to our laboratory on two occasions to undergo testing procedures before and after training sessions, and were then blindly randomized to NLP or LP for 36 training sessions. <i>Visit 1</i> included blood samples and a maximal cardiopulmonary exercise testing to get maximal oxygen uptake (V̇o<sub>2peak</sub>). <i>Visit 2</i> included cognitive functions assessment. Thirty-nine patients completed the study (LP: <i>n</i> = 20, NLP: <i>n</i> = 19), with no observed changes in cognitive performances after the training intervention in either group. IGF-1 concentration decreased in both groups (time-effect: <i>P</i> < 0.001), whereas BDNF concentration increased (time-effect: <i>P</i> < 0.05) without group interaction, and cathepsin-B did not change after the intervention. Associations were found between ΔV̇o<sub>2peak</sub> and ΔBDNF (<i>R</i><sup>2</sup> = 0.18, <i>P</i> = 0.04), and ΔIGF-1 and Δshort-term/working memory (<i>R</i><sup>2</sup> = 0.17, <i>P</i> = 0.01) in the pooled sample, with ΔIGF-1 and ΔBDNF accounting for 10% of the variance in Δshort-term/working memory. In the LP group, associations were found between ΔV̇o<sub>2peak</sub> and ΔBDNF (<i>R</i><sup>2</sup> = 0.45, <i>P</i> = 0.02), ΔBDNF and Δshort-term/working memory (<i>R</i><sup>2</sup> = 0.62, <i>P</i> = 0.004), ΔIGF-1 and Δshort-term/working memory (<i>R</i><sup>2</sup> = 0.31, <i>P</i> = 0.01), and ΔIGF-1 and Δexecutive function (<i>R</i><sup>2</sup> = 0.22, <i>P</i> = 0.04). This study indicates that linear and nonlinear training periodization led to an increase in BDNF, and a decrease in IGF-1, without change in cognitive function in individuals with stable CAD.<b>NEW & NOTEWORTHY</b> We used a novel and supervised iso-energetic training, integrating both moderate- and high-intensity aerobic exercises. Our findings indicate that greater variation in training load did not yield cognitive enhancements, although both protocols exhibited positive effects on brain-derived neurotrophic factor (BDNF) levels. Moreover, this study establishes a clear positive association between short-term and working memory and neurotrophic biomarkers. In addition, the independent predictive value of change in insulin-like growth factor-1 (IGF-1) on improvement in short-term and working memory highlight the close relationship between neurotrophic markers and cognition. Consequently, our results advocate for exercise training interventions targeting neurotrophic biomarkers to enhance cognitive function among individuals with coronary artery disease.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1158-1167"},"PeriodicalIF":3.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11573279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498129","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":"Acute contractile activity induces the activation of the mitochondrial integrated stress response and the transcription factor ATF4.","authors":"Victoria C Sanfrancesco, David A Hood","doi":"10.1152/japplphysiol.00307.2024","DOIUrl":"https://doi.org/10.1152/japplphysiol.00307.2024","url":null,"abstract":"<p><p>Skeletal muscle relies on mitochondria to produce energy and support its metabolic flexibility. The function of the mitochondrial pool is regulated by quality control (MQC) processes. The integrated stress response (ISR), a MQC pathway, is activated in response to various cellular stressors. The transcription factor ATF4, the main effector of the ISR, ameliorates cellular stress by upregulating protective genes, such as CHOP and ATF5. Recent literature has shown that the ISR is activated upon mitochondrial stress, however, whether this includes acute exercise-induced stress is poorly defined. To investigate this, a mouse <i>in situ</i> hindlimb protocol was utilized to acutely stimulate muscles at 0.25, 0.5 and 1 tetanic contraction/per second for 9 mins, followed by a 1-hour recovery period. CAMKII and JNK2 were robustly activated 6-fold immediately following the protocol. ISR activation, denoted as the ratio of phosphorylated to total-eIF2a protein levels, was also elevated following recovery. Downstream, contractile activity induced an increase in the nuclear localization of ATF4. Robust 2-fold increases in the mRNA expression of ATF4 and CHOP were also observed following the recovery period. Changes in ATF4 mRNA were independent of transcriptional activation, as assessed using an ATF4 promoter-reporter plasmid. Instead, mRNA decay assays revealed an increase in ATF4 mRNA stability post-contractile activity, as a result of enhanced stabilization by the RNA binding protein, HuR. Thus, acute contractile activity is sufficient to induce mitochondrial stress and activate the ISR, corresponding to the induction of ATF4 with potential consequences for mitochondrial phenotype adaptations in response to repeated exercise.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466231","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}
Carlos J Munoz, Daniela Lucas, Cynthia R Muller, Jacinda Martinez, Quintin O'Boyle, Ivan S Pires, Andre F Palmer, Pedro Cabrales
{"title":"Coadministration of PEGylated apohemoglobin and haptoglobin can limit vascular dysfunction in the microcirculation and prevent acute inflammation.","authors":"Carlos J Munoz, Daniela Lucas, Cynthia R Muller, Jacinda Martinez, Quintin O'Boyle, Ivan S Pires, Andre F Palmer, Pedro Cabrales","doi":"10.1152/japplphysiol.00315.2024","DOIUrl":"10.1152/japplphysiol.00315.2024","url":null,"abstract":"<p><p>Unfortunately, during pathological conditions resulting in chronic hemolysis cell-free hemoglobin (Hb) is released into the circulation that releases free heme, resulting in several complications. One approach to prevent these toxicities is the administration of supplemental scavenger proteins, haptoglobin (Hp) and hemopexin (Hpx). The goal of this body of work is to objectively measure the levels of vascular reactivity and inflammatory profiles after an infusion of acellular hemoglobin in animals that were given a coadministration of PEGylated human apohemoglobin (PEG-apoHb), a hemopexin (Hpx)-mimetic that can scavenge free heme from hemoglobin, together with human plasma-derived Hp that can scavenge dimerized Hb. Using intravital microscopy, Golden Syrian hamsters instrumented with a dorsal window chamber were used to evaluate the in vivo effects of four experimental groups that were then challenged with a hypovolemic injection (10% of the animal's blood volume) of human Hb (hHb, 5 g/dL). The four experimental groups consisted of: <i>1</i>) lactated Ringer's solution (control), <i>2</i>) PEG-apoHb only, <i>3</i>) Hp only, and <i>4</i>) PEG-apoHb + Hp. The microvascular hemodynamics (diameter and flow) in arterioles and venules were recorded at baseline, 20 min after treatment, and 20 min after hHb challenge. Systemic parameters (blood pressure and heart rate), blood gases (pH, Pco<sub>2</sub>, and Po<sub>2</sub>), blood parameters (Hb concentration and hematocrit), and multiorgan functionality/inflammation were also measured. Our results suggest that coadministration of PEG-apoHb + Hp as a booster before the infusion of acellular hemoglobin significantly prevented vasoconstriction in the microcirculation, significantly increased the number of functional capillaries, and significantly reduced inflammation.<b>NEW & NOTEWORTHY</b> Coadministration of PEGylated human apohemoglobin (PEG-apoHb)-a hemopexin (Hpx) mimetic that can scavenge free heme-and human plasma-derived haptoglobin (Hp) that can scavenge hemoglobin (Hb), reduces microcirculatory dysfunction and cardiac and kidney inflammation in a Hb-challenge model.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"934-944"},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11486475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982299","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":"Is it too hard? Promoting equitable work-life balance.","authors":"L Madden Brewster, Christina D Bruce","doi":"10.1152/japplphysiol.00725.2024","DOIUrl":"https://doi.org/10.1152/japplphysiol.00725.2024","url":null,"abstract":"","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":"137 4","pages":"1064"},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466248","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}
Felipe P Carpes, Daniel Umpierre, Eduardo L Cadore, Fernando Diefenthaeler, Eraldo Pinheiro, Orlando Laitano
{"title":"Career planning in academia: embracing flexibility, failure, and personal growth.","authors":"Felipe P Carpes, Daniel Umpierre, Eduardo L Cadore, Fernando Diefenthaeler, Eraldo Pinheiro, Orlando Laitano","doi":"10.1152/japplphysiol.00681.2024","DOIUrl":"https://doi.org/10.1152/japplphysiol.00681.2024","url":null,"abstract":"","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":"137 4","pages":"1046-1047"},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466245","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":"Do we desire better work-life balance or are we being pragmatic?","authors":"Avery Hinks","doi":"10.1152/japplphysiol.00662.2024","DOIUrl":"https://doi.org/10.1152/japplphysiol.00662.2024","url":null,"abstract":"","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":"137 4","pages":"1053-1054"},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466246","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":"An overlooked skill for trainees: academic task prioritization and time management.","authors":"Steven J Elmer, John J Durocher","doi":"10.1152/japplphysiol.00734.2024","DOIUrl":"https://doi.org/10.1152/japplphysiol.00734.2024","url":null,"abstract":"","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":"137 4","pages":"1052"},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466243","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}
Justin J Duong, Robert G Leija, Adam D Osmond, Jose A Arevalo, George A Brooks
{"title":"Leg cycling efficiency is unaltered in healthy aging regardless of sex or training status.","authors":"Justin J Duong, Robert G Leija, Adam D Osmond, Jose A Arevalo, George A Brooks","doi":"10.1152/japplphysiol.00393.2024","DOIUrl":"10.1152/japplphysiol.00393.2024","url":null,"abstract":"<p><p>Muscular efficiency during exercise has been used to interrogate aspects of human muscle energetics, including mitochondrial coupling and biomechanical efficiencies. Typically, assessments of muscular efficiency have involved graded exercises. Results of previous studies have been interpreted to indicate a decline in exercise efficiency with aging owing to decreased mitochondrial function. However, discrepancies in variables such as exercise stage duration, cycling cadence, and treadmill walking mechanics may have affected interpretations of results. Furthermore, recent data from our lab examining the ATP to oxygen ratio (P:O) in mitochondrial preparations isolated from NIA mouse skeletal muscle showed no change with aging. Thus, we hypothesized that delta efficiency (Δ€) during steady-rate cycling exercise would not be altered in older healthy subjects compared with young counterparts regardless of biological sex or training status. Young (21-35 yr) and older (60-80 yr) men (<i>n</i> = 21) and women (<i>n</i> = 20) underwent continual, progressive leg cycle ergometer tests pedaling at 60 RPM for three stages (35, 60, 85 W) lasting 4 min. Δ€was calculated as: (Δ work accomplished/Δ energy expended). Overall, cycling efficiencies were not significantly different in older compared with young subjects. Similarly, trained subjects did not exhibit significantly different exercise efficiencies compared to untrained. Moreover, there were no differences between men and women. Hence, our results obtained on healthy young and older subjects are interpreted to mean that previous reports of decreased efficiency in older individuals were attributable to metabolic or biomechanical comorbidities, not aging per se.<b>NEW & NOTEWORTHY</b> Muscular power is reduced, but the efficiency of movement is unaltered in healthy aging.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"857-863"},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11486473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874955","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}