Sarah J Hammond, Andrea J Roff, Joshua L Robinson, Jack R T Darby, Ashley S Meakin, Vicki L Clifton, Robert J Bischof, Michael J Stark, Megan J Wallace, Andrew Tai, Janna L Morrison, Kathryn L Gatford
{"title":"In utero exposure to experimental maternal asthma alters fetal airway development in sheep.","authors":"Sarah J Hammond, Andrea J Roff, Joshua L Robinson, Jack R T Darby, Ashley S Meakin, Vicki L Clifton, Robert J Bischof, Michael J Stark, Megan J Wallace, Andrew Tai, Janna L Morrison, Kathryn L Gatford","doi":"10.1113/EP092502","DOIUrl":"https://doi.org/10.1113/EP092502","url":null,"abstract":"<p><p>The mechanisms linking maternal asthma (MA) exposure in utero and subsequent risk of asthma in childhood are not fully understood. Pathological airway remodelling, including reticular basement membrane thickening, has been reported in infants and children who go on to develop asthma later in childhood. This suggests altered airway development before birth as a mechanism underlying increased risk of asthma in children exposed in utero to MA. We hypothesised that in utero MA exposure would reduce airway diameter and increase airway-associated smooth muscle area and reticular basement membrane thickness in neonatal offspring. Experimental MA was induced by maternal sensitisation followed by airway challenges with house dust mite before and during pregnancy. Lambs from control (n = 16) or MA (n = 26) ewes were delivered at ∼140 days gestation (term = 150 days), ventilated for 45 min, then humanely killed. Left lungs were inflation-fixed, and cross-sections of generation 2-5 airways were collected. Airway sections were stained with Haematoxylin and Eosin, Masson's Trichrome and Gordon and Sweet's histological stains for morphological analysis. Lamb body and lung weights were similar between groups (P > 0.5 and P > 0.7, respectively). Lambs that were exposed to MA had narrower airway diameters (P = 0.019) and thinner reticular basement membrane (P = 0.016) but similar airway-associated smooth muscle area (P = 0.152) compared with unexposed control lambs. Our results demonstrate a potential mechanism for increased risk of asthma in children of mothers with asthma, independent of genetic risk or behavioural changes during pregnancy.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052032","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":"The ins and outs of liver fat metabolism: The effect of phenotype and diet on risk of intrahepatic triglyceride accumulation.","authors":"Kieran Smith, Kaitlyn M J H Dennis, Leanne Hodson","doi":"10.1113/EP092001","DOIUrl":"https://doi.org/10.1113/EP092001","url":null,"abstract":"<p><p>In health, the liver is a metabolically flexible organ that plays a key role in regulating systemic lipid and glucose concentrations. There is a constant flux of fatty acids (FAs) to the liver from multiple sources, including adipose tissue, dietary, endogenously synthesized from non-lipid precursors, intrahepatic lipid droplets and recycling of triglyceride-rich remnants. Within the liver, FAs are used for triglyceride synthesis, which can be oxidized, stored or secreted in very low-density lipoproteins into the systemic circulation. The processes of FA uptake, FA synthesis and the intracellular partitioning of FAs into storage, oxidation or secretory pathways are tightly regulated. An imbalance in these processes causes intrahepatic triglyceride to accumulate and is associated with the development of metabolic dysfunction-associated steatotic liver disease. It is well appreciated that many factors can influence intrahepatic FA partitioning, and although there is good evidence that both phenotype (e.g., sex, ethnicity and adiposity) and dietary macronutrient composition can play a role in intrahepatic triglyceride accumulation, their interaction remains poorly understood. The aim of this review is to explore how the respective pathways of FA delivery, synthesis and disposal are altered by phenotype and understand how dietary macronutrient composition might influence the partitioning of FAs in the liver in vivo, in humans.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143037729","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}
Thamali Ayagama, Peregrine G Green, Cheryl Tan, Cristiana Monteiro, David A Holdsworth, Neil Herring
{"title":"Circulating neuropeptide Y dynamics and performance during exercise in heart failure patients with contemporary medical and device therapy.","authors":"Thamali Ayagama, Peregrine G Green, Cheryl Tan, Cristiana Monteiro, David A Holdsworth, Neil Herring","doi":"10.1113/EP092325","DOIUrl":"https://doi.org/10.1113/EP092325","url":null,"abstract":"<p><p>High cardiac sympathetic drive and release of the sympathetic cotransmitter neuropeptide Y (NPY) are significant features of congestive heart failure (CHF), in which resting venous NPY levels are known to be associated with mortality. However, whether circulating NPY levels increase during exercise in CHF when they are already elevated is controversial. We sought to establish the dynamics of circulating NPY levels in CHF patients treated with contemporary medical therapy and devices in relationship to indices of performance linked to long-term prognosis. CHF patients (n = 15) underwent cardiopulmonary exercise testing with venous blood sampling at rest, peak exercise and recovery. These patients had significantly higher resting venous NPY levels compared with an age- and sex-matched control group of patients (n = 16) with normal left ventricular function (40 ± 6.9 vs. 9.0 ± 4.6 pg/mL, respectively; P < 0.0001). In CHF patients, NPY levels increased significantly from baseline to peak exercise (to 93.5 ± 42.1 pg/mL; P = 0.0004) and remained elevated during recovery (86.8 ± 44.6 pg/mL; P = 0.0018). The peak (r = 0.58, P = 0.0222) and recovery (r = 0.56, P = 0.0304) NPY levels and the ability to increase NPY from baseline (r = 0.53, P = 0.0427) showed significant positive correlations with heart rate recovery at 1 min, but not with peak oxygen consumption. In CHF patients, the ability to increase NPY levels on exertion is correlated with heart rate recovery, a known prognostic indicator for mortality. These findings suggest that NPY dynamics during exercise might provide valuable insights into sympathetic responses and prognosis in CHF patients.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143037728","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}
Edouard Marques, Etienne J Couture, Jean S Bussières, Stephan Langevin, Paul Poirier, Pierre Voisine, Manon Caouette, Patrice Brassard
{"title":"Effects of noradrenaline and phenylephrine on cerebral oxygen saturation during cardiopulmonary bypass in cardiac surgery.","authors":"Edouard Marques, Etienne J Couture, Jean S Bussières, Stephan Langevin, Paul Poirier, Pierre Voisine, Manon Caouette, Patrice Brassard","doi":"10.1113/EP092387","DOIUrl":"https://doi.org/10.1113/EP092387","url":null,"abstract":"<p><p>Cardiopulmonary bypass (CPB) in cardiac surgery is associated with a high risk of postoperative neurological complications. Perioperative use of vasopressors is common to counteract arterial hypotension in this setting. However, use of α-agonist vasopressors has been associated with cerebral desaturations. Given that reductions in cerebral oxygen saturation ( <math> <semantics><msub><mi>S</mi> <mrow><mi>c</mi> <msub><mi>O</mi> <mn>2</mn></msub> </mrow> </msub> <annotation>${S_{{mathrm{c}}{{mathrm{O}}_2}}}$</annotation></semantics> </math> ) can increase postoperative neurological dysfunction, we aimed to investigate the impact of noradrenaline (NA) and phenylephrine (PE) on <math> <semantics><msub><mi>S</mi> <mrow><mi>c</mi> <msub><mi>O</mi> <mn>2</mn></msub> </mrow> </msub> <annotation>${S_{{mathrm{c}}{{mathrm{O}}_2}}}$</annotation></semantics> </math> during the CPB period of a cardiac surgery in 36 patients scheduled for an elective cardiac surgery. Patients were randomized to the intra-operative use of either NA or PE. During CPB, mean arterial pressure (MAP) was elevated pharmacologically to predefined thresholds of 60 and 80 mmHg, while CPB flow was kept constant. The <math> <semantics><msub><mi>S</mi> <mrow><mi>c</mi> <msub><mi>O</mi> <mn>2</mn></msub> </mrow> </msub> <annotation>${S_{{mathrm{c}}{{mathrm{O}}_2}}}$</annotation></semantics> </math> values were recorded for 5 min per MAP threshold. The MAP increased adequately between thresholds of 60 and 80 mmHg (NA, 59 ± 3 vs. 81 ± 3 mmHg and PE, 61 ± 4 vs. 81 ± 3 mmHg; P ˂ 0.01). The <math> <semantics><msub><mi>S</mi> <mrow><mi>c</mi> <msub><mi>O</mi> <mn>2</mn></msub> </mrow> </msub> <annotation>${S_{{mathrm{c}}{{mathrm{O}}_2}}}$</annotation></semantics> </math> decreased between pressure thresholds of 60 and 80 mmHg (NA, 70 ± 11 vs. 69 ± 11 mmHg and PE, 64 ± 11 vs. 63 ± 11 mmHg; P ˂ 0.01). Reduction in <math> <semantics><msub><mi>S</mi> <mrow><mi>c</mi> <msub><mi>O</mi> <mn>2</mn></msub> </mrow> </msub> <annotation>${S_{{mathrm{c}}{{mathrm{O}}_2}}}$</annotation></semantics> </math> did not differ between vasopressors. The mean relative decrease in <math> <semantics><msub><mi>S</mi> <mrow><mi>c</mi> <msub><mi>O</mi> <mn>2</mn></msub> </mrow> </msub> <annotation>${S_{{mathrm{c}}{{mathrm{O}}_2}}}$</annotation></semantics> </math> across groups was 2.0% (95% confidence interval: 0.6 to 2.1). Elevation in MAP mediated solely by vasopressors induces significant decreases in <math> <semantics><msub><mi>S</mi> <mrow><mi>c</mi> <msub><mi>O</mi> <mn>2</mn></msub> </mrow> </msub> <annotation>${S_{{mathrm{c}}{{mathrm{O}}_2}}}$</annotation></semantics> </math> during cardiac surgery under CPB. However, their impact on <math> <semantics><msub><mi>S</mi> <mrow><mi>c</mi> <msub><mi>O</mi> <mn>2</mn></msub> </mrow> </msub> <annotation>${S_{{mathrm{c}}{{mathrm{O}}_2}}}$</annotation></semantics> </math> remains clinically non-significant according to current guidelines.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032695","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":"Critical power: An important tool for exercise prescription and the assessment of physiological function.","authors":"Daniel Muniz Pumares, Samuel Meyler","doi":"10.1113/EP092258","DOIUrl":"https://doi.org/10.1113/EP092258","url":null,"abstract":"","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022605","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}
Carmen Possnig, Kyohei Marume, Gautam Babu, Sylvan L J E Janssen, Christopher M Hearon, Katrin A Dias, Satyam Sarma, Justin S Lawley, Benjamin D Levine
{"title":"Regional changes in cerebral blood flow between the upright and supine posture and over 3 days of bed rest.","authors":"Carmen Possnig, Kyohei Marume, Gautam Babu, Sylvan L J E Janssen, Christopher M Hearon, Katrin A Dias, Satyam Sarma, Justin S Lawley, Benjamin D Levine","doi":"10.1113/EP091820","DOIUrl":"https://doi.org/10.1113/EP091820","url":null,"abstract":"<p><p>A reduction in cerebral blood flow (CBF) has been observed during spaceflight and bed rest. We aimed to examine the magnitude and regional heterogeneity of the decrease in CBF during bed rest compared to posture changes on Earth. Seventeen participants (age, 29 ± 9 years, 7 females) were studied in the upright and supine posture and over 3 days of bed rest. We assessed blood flow via duplex ultrasonography in the internal carotid (ICA) and vertebral arteries (VA), and via transcranial Doppler of the middle cerebral artery (MCAv). Mean arterial pressure (MAP) and end-tidal CO<sub>2</sub> ( <math> <semantics><mrow><mi>E</mi> <msub><mi>T</mi> <mrow><mi>C</mi> <msub><mi>O</mi> <mn>2</mn></msub> </mrow> </msub> </mrow> <annotation>${mathrm{E}}{{{mathrm{T}}}_{{mathrm{C}}{{{mathrm{O}}}_{mathrm{2}}}}}$</annotation></semantics> </math> ) were assessed at all time points. By day 3, total CBF (1078 ± 302 to 853 ± 245 mL min<sup>-1</sup>, P < 0.0001) and MCAv (61 ± 15 to 49 ± 12 mL min<sup>-1</sup>, P < 0.0001) were decreased compared to the supine posture. CBF values did not fall below the upright posture (all P > 0.05) but were lower than a calculated 24-h mean baseline (P = 0.0132). MAP remained stable (P = 0.971), as did <math> <semantics><mrow><mi>E</mi> <msub><mi>T</mi> <mrow><mi>C</mi> <msub><mi>O</mi> <mn>2</mn></msub> </mrow> </msub> </mrow> <annotation>${mathrm{E}}{{{mathrm{T}}}_{{mathrm{C}}{{{mathrm{O}}}_{mathrm{2}}}}}$</annotation></semantics> </math> (P = 0.0803), while VA blood flow decreased after 24 h and again after 72 h (P = 0.0024). These findings indicate that CBF decreases during short-term bed rest, but not below values observed in the upright posture.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022670","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}
Mikaela L Frechette, Summer B Cook, Brendan R Scott, Jane Tan, Ann-Maree Vallence
{"title":"Post-exercise neural plasticity is augmented by adding blood flow restriction during low work rate arm cycling.","authors":"Mikaela L Frechette, Summer B Cook, Brendan R Scott, Jane Tan, Ann-Maree Vallence","doi":"10.1113/EP092113","DOIUrl":"https://doi.org/10.1113/EP092113","url":null,"abstract":"<p><p>Blood flow restriction (BFR) combined with low work rate exercise can enhance muscular and cardiovascular fitness. However, whether neural mechanisms mediate these enhancements remains unknown. This study examined changes in corticospinal excitability and motor cortical inhibition following arm cycle ergometry with and without BFR. Twelve healthy males (24 ± 4 years) completed four, randomized 15-min arm cycling conditions: high work rate (HW: 60% maximal power output), low work rate (LW: 30% maximal power output), low work rate with BFR (LW-BFR) and BFR without exercise (BFR-only). For BFR conditions, cuffs were applied around the upper arm and inflated to 70% of arterial occlusion pressure continuously during exercise. Single-pulse transcranial magnetic stimulation was delivered to left primary motor cortex (M1) to elicit motor-evoked potentials (MEP) in the right biceps brachii during a low-level isometric contraction. MEP amplitude and cortical silent period (cSP) duration were measured before and 1, 10 and 15 min post-exercise. MEP amplitude increased significantly from baseline to Post-10 and Post-15 for both the HW (both z < -7.07, both P < 0.001) and LW-BFR conditions (both z < -5.56, both P < 0.001). For the LW condition without BFR, MEP amplitude increased significantly from baseline to Post-10 (z = -3.53, P = 0.003) but not Post-15 (z = -1.85, P = 0.388). The current findings show that HW arm cycling and LW-BFR led to longer-lasting increases in corticospinal excitability than LW arm cycling alone. Future research should examine whether the increased corticospinal excitability is associated with the improvements in muscle strength observed with BFR exercise. A mechanistic understanding of BFR exercise improvement could guide BFR interventions in clinical populations.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002772","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":"Are we prematurely predicting acute mountain sickness?","authors":"Julian C Bommarito, Michael M Tymko","doi":"10.1113/EP092490","DOIUrl":"https://doi.org/10.1113/EP092490","url":null,"abstract":"","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002707","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":"Comments on Rajizadeh et al. (2023) 'Comparison of preventive and therapeutic effects of continuous exercise on acute lung injury induced with methotrexate'.","authors":"Mehran Hosseini","doi":"10.1113/EP092385","DOIUrl":"https://doi.org/10.1113/EP092385","url":null,"abstract":"","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002712","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}