Robin Christensen, Tobias Haugegaard, Janus C Jakobsen
{"title":"Role of prespecified analysis plans in physiological research: Encouraged or mandatory?","authors":"Robin Christensen, Tobias Haugegaard, Janus C Jakobsen","doi":"10.1113/EP092034","DOIUrl":"https://doi.org/10.1113/EP092034","url":null,"abstract":"","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michele Girardi, Carlo Capelli, Carrie Ferguson, Susan A Ward, Harry B Rossiter
{"title":"Breath-by-breath measurement of alveolar gas exchange must preserve mass balance and conform to a physiological definition of a breath.","authors":"Michele Girardi, Carlo Capelli, Carrie Ferguson, Susan A Ward, Harry B Rossiter","doi":"10.1113/EP092221","DOIUrl":"https://doi.org/10.1113/EP092221","url":null,"abstract":"<p><p>Tidal breathing in awake humans is variable. This variability causes changes in lung gas stores that affect gas exchange measurements. To overcome this, several algorithms provide solutions for breath-by-breath alveolar gas exchange measurement; however, there is no consensus on a physiologically robust method suitable for widespread application. A recent approach, the 'independent-breath' (IND) algorithm, avoids the complexity of measuring breath-by-breath changes in lung volume by redefining what is meant by a 'breath'. Specifically, it defines a single breathing cycle as the time between equal values of the <math> <semantics><msub><mi>F</mi> <msub><mi>O</mi> <mn>2</mn></msub> </msub> <annotation>${F_{{{mathrm{O}}_2}}}$</annotation></semantics> </math> / <math> <semantics><msub><mi>F</mi> <msub><mi>N</mi> <mn>2</mn></msub> </msub> <annotation>${F_{{{mathrm{N}}_2}}}$</annotation></semantics> </math> (or <math> <semantics><msub><mi>F</mi> <mrow><mi>C</mi> <msub><mi>O</mi> <mn>2</mn></msub> </mrow> </msub> <annotation>${F_{{mathrm{C}}{{mathrm{O}}_2}}}$</annotation></semantics> </math> / <math> <semantics><msub><mi>F</mi> <msub><mi>N</mi> <mn>2</mn></msub> </msub> <annotation>${F_{{{mathrm{N}}_2}}}$</annotation></semantics> </math> ) ratio, that is, the ratio of fractional concentrations of lung-expired O<sub>2</sub> (or CO<sub>2</sub>) and nitrogen (N<sub>2</sub>). These developments imply that the end of one breath is not, by necessity, aligned with the start of the next. Here we demonstrate how the use of the IND algorithm fails to conserve breath-by-breath mass balance of O<sub>2</sub> and CO<sub>2</sub> exchanged between the atmosphere and tissues (and vice versa). We propose a new term, within the IND algorithm, designed to overcome this limitation. We also present the far-reaching implications of using algorithms based on alternative definitions of the breathing cycle, including challenges in measuring and interpreting the respiratory exchange ratio, pulmonary gas exchange efficiency, dead space fraction of the breath, control of breathing, and a broad spectrum of clinically relevant cardiopulmonary exercise testing variables. Therefore, we do not support the widespread adoption of currently available alternative definitions of the breathing cycle as a legitimate solution for breath-by-breath alveolar gas exchange measurement in research or clinical settings.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A method for dyadic cardiac rhythmicity analysis: Preliminary evidence on bilateral interactions in fetal-maternal cardiac dynamics.","authors":"Diego Candia-Rivera, Mario Chavez","doi":"10.1113/EP092532","DOIUrl":"https://doi.org/10.1113/EP092532","url":null,"abstract":"<p><p>Cardiac activity responds dynamically to metabolic demands and neural regulation. However, little is known about this process during pregnancy. Reports show occasional fetal-maternal heart rate couplings, but it has remained unclear whether these couplings extend to more complex oscillatory patterns of the heart rhythm. We developed a framework of time-varying measures of heart rate and rhythm, to test the presence of co-varying patterns in concurrent maternal and fetal measures (late pregnancy dataset, n = 10, and labour dataset, n = 12). These measures were derived from first and second-order Poincaré plots, with the aim to describe changes in short- and long-term rhythmicity, but also the dynamic shifts in acceleration and deceleration of heart rate. We found episodes of maternal-fetal co-varying patterns of cardiac rhythm in all the measures explored, in both datasets (at least 90% of the dataset presented a significant maternal-fetal correlation in each measure, with P < 0.001), with dynamic delays suggesting bilateral interactions at different time scales. We also found that these couplings intensify during labour (test between late pregnancy vs. labour datasets, P < 0.0015 in all second-order Poincaré plot-derived measures). While most literature suggests that the fetal heart responds to maternal breathing patterns or contractions, we propose the possibility that the fetal heart may also have a signalling function in the context of co-regulatory mechanisms and maternal inter-organ interactions. Understanding these complex visceral oscillations in utero may enhance the assessment of a healthy fetal development.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Simon Nørskov Thomsen, Emil Wriedt, Marianne Gardar Stærk, Sissal Sigmundsdottir Djurhuus, Birgitte Grønkær Toft, Sabrina Wielsøe, Andreas Røder, Thomas Hasselager, Peter Busch Østergren, Henrik Jakobsen, Klaus Brasso, Jesper Frank Christensen, Louise Lang Lehrskov, Casper Simonsen
{"title":"Impact of exercise training on tumour-infiltrating T cells in human prostate cancer: A secondary analysis of a randomized controlled trial (PRO-TEST).","authors":"Simon Nørskov Thomsen, Emil Wriedt, Marianne Gardar Stærk, Sissal Sigmundsdottir Djurhuus, Birgitte Grønkær Toft, Sabrina Wielsøe, Andreas Røder, Thomas Hasselager, Peter Busch Østergren, Henrik Jakobsen, Klaus Brasso, Jesper Frank Christensen, Louise Lang Lehrskov, Casper Simonsen","doi":"10.1113/EP092374","DOIUrl":"https://doi.org/10.1113/EP092374","url":null,"abstract":"<p><p>Exercise training reduces tumour growth by increasing tumour-infiltrating T-cell density in preclinical models. However, it remains unknown whether exercise training can modify intratumoural T cells in humans.The aim of this study was to compare the effects of an exercise training intervention versus control on human prostate intratumoural T-cell density.This study is a secondary analysis of a randomized controlled trial. We randomly allocated men (age > 18 years) with treatment-naive localized prostate cancer scheduled for radical prostatectomy 2:1 to exercise training intervention or control. The exercise intervention consisted of supervised, high-intensity interval bicycling four times per week from the time of randomization until prostatectomy. Intratumoural CD3<sup>+</sup> and CD8<sup>+</sup> T-cell densities in diagnostic biopsies and postsurgical prostatectomy specimens were quantified using immunohistochemistry. Between-group differences in changes from baseline to follow-up were estimated using constrained baseline linear mixed-effect models.A total of 30 participants were included (exercise intervention, n = 20; control, n = 10). We found no between-group differences in changes in CD3<sup>+</sup> T cells [mean difference (95% confidence interval): -17 (-185; 150) cells/mm<sup>2</sup>] or CD8<sup>+</sup> T cells [mean difference (95% confidence interval): -16 (-206; 172) cells/mm<sup>2</sup>]. Additionally, we found no statistically significant correlations between changes in T-cell density and the number of exercise training sessions attended or changes in maximal oxygen consumption.In this secondary analysis of a randomized controlled trial, we found no impact of the exercise regimen on tumour-infiltrating CD3<sup>+</sup> and CD8<sup>+</sup> T-cell density in human prostate cancer.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"From bedside to seaside: An academic's attempt at freediving.","authors":"Anthony R Bain","doi":"10.1113/EP092405","DOIUrl":"https://doi.org/10.1113/EP092405","url":null,"abstract":"","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gian Domenico Pinna, Elena Robbi, Maria Teresa La Rovere, Roberto Maestri
{"title":"Heart rate response to transient hypoxia in patients with heart failure and Cheyne-Stokes respiration.","authors":"Gian Domenico Pinna, Elena Robbi, Maria Teresa La Rovere, Roberto Maestri","doi":"10.1113/EP092304","DOIUrl":"https://doi.org/10.1113/EP092304","url":null,"abstract":"<p><p>Cheyne-Stokes respiration (CSR), a rhythmic rise and fall in ventilation often experienced by patients with heart failure during sleep, is typically accompanied by an oscillation in heart rate (HR) at the same frequency. The mechanisms responsible for this oscillation are still debated. In this study, we used the experimental model of the transient hypoxia test (i.e., a laboratory test that mimics the transient nature of the cyclic desaturations that occur during hyperpnoeic phases of CSR) to assess accurately the temporal relationship between the HR response to transient hypoxia and the tidal volume response in six heart failure patients. The same relationship was assessed during CSR using polysomnographic signals. We hypothesized that this relationship would provide important insights into the key mechanisms contributing to the HR response. During transient hypoxia, HR started to increase around the onset of tidal volume increase but continued to increase after the peak of the latter had been reached. The time delay between the two peaks (HR vs. tidal volume) was 7.9 ± 4.8 s. The same delay during hyperpnoeic phases of CSR was 1.0 ± 0.9 s. In addition, the increases in lung volume were much greater than those found in the laboratory tests. Based on the known dynamics of vagal and sympathetic control of HR, we speculate that the HR response to transient hypoxia might be attributable predominantly to the sympathetically mediated tachycardic effect of the increased central inspiratory drive, whereas the fast, vagally mediated pulmonary inflation reflex might be the predominant mechanism during CSR.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Preemptive iodide treatment in the event of a nuclear disaster: The prepper's guide to the galaxy.","authors":"Per Karkov Cramon, Søren Holm, Ronan M G Berg","doi":"10.1113/EP092154","DOIUrl":"https://doi.org/10.1113/EP092154","url":null,"abstract":"","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jacky Soo, Paul Goods, Olivier Girard, Louise Deldicque, Nathan G Lawler, Timothy J Fairchild
{"title":"Exercise responses to perceptually regulated high intensity interval exercise with continuous and intermittent hypoxia in inactive overweight individuals.","authors":"Jacky Soo, Paul Goods, Olivier Girard, Louise Deldicque, Nathan G Lawler, Timothy J Fairchild","doi":"10.1113/EP092338","DOIUrl":"https://doi.org/10.1113/EP092338","url":null,"abstract":"<p><p>To investigate the acute effects of hypoxia applied during discrete work and recovery phases of a perceptually regulated, high-intensity interval exercise (HIIE) on external and internal loads in inactive overweight individuals. On separate days, 18 inactive overweight (28.7 ± 3.3 kg m<sup>-2</sup>; 31 ± 8 years) men and women completed a cycling HIIE protocol (6 × 1 min intervals with 4 min active recovery, maintaining a perceived rating of exertion of 16 and 10 during work and recovery, respectively, on the 6-20 Borg scale) in randomized conditions: normoxia (NN), normobaric hypoxia (inspired O<sub>2</sub> fraction ∼0.14) during both work and recovery (HH), hypoxia during recovery (NH) and hypoxia during work only (HN). Markers of external (relative mean power output, MPO) and internal load (blood lactate concentration, heart rate and tissue saturation index (TSI)) were measured. MPO was lower in HH compared to NN, NH and HN (all P < 0.001), with HN also being lower than NN (P < 0.001) and NH (P < 0.023). Heart rate was higher in HN than NN, HH and NH (all P < 0.001). Blood lactate response was higher in NN than HH (P = 0.003) and NH (P = 0.008). Changes in the TSI area above the curve were greater in HN relative to NN, HH and NH (all P < 0.001). Hypoxia applied intermittently during the work or recovery phases may mitigate the declines in mechanical output observed when exercise is performed in continuous hypoxia, although hypoxia implemented during the work phase resulted in elevated heart rate and lactate response. Specifically, exercise performance largely comparable to that in normoxia can be achieved when hypoxia is implemented exclusively during recovery.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Oliver R Gibson, Orlando Laitano, Kazuhito Watanabe, José González-Alonso
{"title":"Differential intestinal injury and unchanged systemic inflammatory responses to leg and whole-body passive hyperthermia in healthy humans.","authors":"Oliver R Gibson, Orlando Laitano, Kazuhito Watanabe, José González-Alonso","doi":"10.1113/EP092389","DOIUrl":"https://doi.org/10.1113/EP092389","url":null,"abstract":"<p><p>Hyperthermia can cause intestinal injury, facilitating endotoxin translocation and an inflammatory response that has been associated with heat illness. However, the potential occurrence of these responses has been incompletely reported during passive hyperthermia, and the independent effect of hyperthermia is equivocal. Furthermore, passive hyperthermia is a feature of heat therapy interventions, with mechanistic understanding developing. This experiment quantified the changes in intestinal fatty acid binding protein (iFABP), a marker of intestinal injury, and cytokine, chemokine and growth factor responses during three different prolonged passive hyperthermia protocols. Eight healthy males visited the laboratory on four counterbalanced occasions to undertake 2.5 h of rest (CON), one-leg heating (OLH), two-leg heating (TLH) and whole-body heating (WBH) via a garment circulating water at 50°C. Plasma concentrations of iFABP and 38 cytokines, chemokines and growth factors were quantified periodically, and core temperature (T<sub>core</sub>) was measured continuously. The T<sub>core</sub> increased from baseline in OLH, TLH and WBH (+0.4°C ± 0.2°C, +0.7°C ± 0.2°C and +2.3°C ± 0.4°C, respectively; P < 0.05) but remained unchanged in CON. iFABP increased from baseline in WBH only (∆587 ± 651 pg ml<sup>-1</sup>) and was different from CON and OLH in WBH after 2 h (P < 0.05). Increased iFABP (∆1085 ± 572 pg ml<sup>-1</sup>) was observed in 50% of participants at the end of WBH, with the other 50% demonstrating no change (∆89 ± 19 pg ml<sup>-1</sup>). All chemokines, cytokines and growth factors were unchanged in all protocols. These data indicate that passive whole-body hyperthermia, but not lower-limb hyperthermia, can cause intestinal injury in some individuals without a systemic inflammatory response.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}