Acta Physiologica最新文献

{"title":"HIF-1α limits myocardial infarction by promoting mitophagy in mouse hearts adapted to chronic hypoxia","authors":"Petra Alanova,&nbsp;Lukas Alan,&nbsp;Barbora Opletalova,&nbsp;Romana Bohuslavova,&nbsp;Pavel Abaffy,&nbsp;Katerina Matejkova,&nbsp;Kristyna Holzerova,&nbsp;Daniel Benak,&nbsp;Nina Kaludercic,&nbsp;Roberta Menabo,&nbsp;Fabio Di Lisa,&nbsp;Bohuslav Ostadal,&nbsp;Frantisek Kolar,&nbsp;Gabriela Pavlinkova","doi":"10.1111/apha.14202","DOIUrl":"10.1111/apha.14202","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The transcriptional factor HIF-1α is recognized for its contribution to cardioprotection against acute ischemia/reperfusion injury. Adaptation to chronic hypoxia (CH) is known to stabilize HIF-1α and increase myocardial ischemic tolerance. However, the precise role of HIF-1α in mediating the protective effect remains incompletely understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Male wild-type (WT) mice and mice with partial <i>Hif1a</i> deficiency (<i>hif1a</i>\u0000 ^+/−) were exposed to CH for 4 weeks, while their respective controls were kept under normoxic conditions. Subsequently, their isolated perfused hearts were subjected to ischemia/reperfusion to determine infarct size, while RNA-sequencing of isolated cardiomyocytes was performed. Mitochondrial respiration was measured to evaluate mitochondrial function, and western blots were performed to assess mitophagy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We demonstrated enhanced ischemic tolerance in WT mice induced by adaptation to CH compared with their normoxic controls and chronically hypoxic <i>hif1a</i>\u0000 ^+/− mice. Through cardiomyocyte bulk mRNA sequencing analysis, we unveiled significant reprogramming of cardiomyocytes induced by CH emphasizing mitochondrial processes. CH reduced mitochondrial content and respiration and altered mitochondrial ultrastructure. Notably, the reduced mitochondrial content correlated with enhanced autophagosome formation exclusively in chronically hypoxic WT mice, supported by an increase in the LC3-II/LC3-I ratio, expression of PINK1, and degradation of SQSTM1/p62. Furthermore, pretreatment with the mitochondrial division inhibitor (mdivi-1) abolished the infarct size-limiting effect of CH in WT mice, highlighting the key role of mitophagy in CH-induced cardioprotection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings provide new insights into the contribution of HIF-1α to cardiomyocyte survival during acute ischemia/reperfusion injury by activating the selective autophagy pathway.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14202","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141625376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased water intake dilutes protective uromodulin levels in urine and results in increased rates of pyelonephritis in a murine model","authors":"Aimi D. K. Hamilton,&nbsp;Laura V. Sparsoe,&nbsp;Mathias Skov,&nbsp;Nanna Johnsen,&nbsp;Mette H. Chreistensen,&nbsp;Thomas J. Corydon,&nbsp;Helle Praetorius","doi":"10.1111/apha.14204","DOIUrl":"10.1111/apha.14204","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Urinary tract infections (UTIs) rank among the most prevalent infections in humans, carrying substantial implications for public health. Women experiencing recurrent UTIs are often advised to boost their fluid intake to help eliminate bacteria. In this study, we explored the impact of elevated fluid consumption during UTIs using a mouse model of pyelonephritis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>UTI was induced in 8–10 w female BALB/cJ-mice by surgically injecting <i>Escherichia coli</i> (O6:K13:H1) into the bladder whereafter mice were randomized to gel food (GF) or regular chow. Immune response and infection severity were determined 24-h post-infection. In vitro bacterial growth (OD₆₀₀) was determined in urine from mice or from human volunteers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Gel feeding increased urine output (1.40 ± 0.77 μL min⁻¹, <i>p</i> &lt; 0.01) and diluted the urine (668.7 ± 177 mOsmol kg⁻¹, <i>p</i> &lt; 0.0001) compared to controls on regular chow (urine output: 0.34 ± 0.27 μL min⁻¹, osmolality: 1439 ± 473.5 mOsmol kg⁻¹). Mice on GF had a higher risk of pyelonephritis (87.5%) and more severe infections (26.22 ± 9.88 CFU mg⁻¹ tissue) compared to controls (43.75%; 3.87 ± 3.56 CFU mg⁻¹, <i>p</i> &lt; 0.01). Correspondingly, the growth <i>of E. coli</i> was markedly reduced at osmolalities above 1200 mOsmol kg⁻¹ compared to 600 mOsmol kg⁻¹ and GF mice had lower urine levels of uromodulin (13.70 ± 1.89 μg mL⁻¹, <i>p</i> &lt; 0.01) compared to controls (24.65 ± 2.70 μg mL⁻¹).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Increased water intake and urine flow in mice will markedly increase the risk of pyelonephritis. The increased risk may reflect reduced urine uromodulin combined with optimized growth conditions for <i>E. coli</i>. The study does not immediately support the notion that established UTIs can be eliminated by increased water intake.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14204","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141615349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endothelial histone deacetylase 1 activity impairs kidney microvascular NO signaling in rats fed a high-salt diet","authors":"Luke S. Dunaway,&nbsp;Anthony K. Cook,&nbsp;Cailin E. Kellum,&nbsp;Claudia Edell,&nbsp;Davide Botta,&nbsp;Patrick A. Molina,&nbsp;Randee S. Sedaka,&nbsp;Livius V. d'Uscio,&nbsp;Zvonimir S. Katusic,&nbsp;David M. Pollock,&nbsp;Edward W. Inscho,&nbsp;Jennifer S. Pollock","doi":"10.1111/apha.14201","DOIUrl":"10.1111/apha.14201","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>We aimed to test the hypothesis that a high-salt diet (HS) impairs NO signaling in kidney microvascular endothelial cells through a histone deacetylase 1 (HDAC1)-dependent mechanism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Male Sprague Dawley rats were fed normal salt diet (NS; 0.49% NaCl) or HS (4% NaCl) for 2 weeks. NO signaling was assessed by measuring L-NAME induced vasoconstriction of the afferent arteriole using the blood perfused juxtamedullary nephron (JMN) preparation. In this preparation, kidneys were perfused with blood from a donor rat on a matching or different diet to that of the kidney donor. Kidney endothelial cells were isolated with magnetic activated cell sorting and HDAC1 activity was measured.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found HS-induced impaired NO signaling in the afferent arteriole. This was restored by inhibition of HDAC1 with MS-275. Consistent with these findings, HDAC1 activity was increased in kidney endothelial cells. We further found the loss of NO to be dependent upon the diet of the blood donor rather than the diet of the kidney donor and the plasma from HS-fed rats to be sufficient to induce impaired NO signaling. This indicates the presence of a humoral factor we termed plasma-derived endothelial dysfunction mediator (PDEM). Pretreatment with the antioxidants, PEG-SOD and PEG-catalase, as well as the NOS cofactor, tetrahydrobiopterin, restored NO signaling.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We conclude that HS activates endothelial HDAC1 through PDEM leading to decreased NO signaling. This study provides novel insights into the molecular mechanisms by which a HS decreases renal microvascular endothelial NO signaling.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14201","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141615348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physiological programming, adaptation, and regeneration","authors":"Pontus B. Persson,&nbsp;Anja Bondke Persson","doi":"10.1111/apha.14207","DOIUrl":"10.1111/apha.14207","url":null,"abstract":"&lt;p&gt;Physiologically occurring programming processes, inherent within biological systems, govern the development and function of organisms. Driven by genetic and epigenetic factors, these processes dictate cellular differentiation, organ development, and physiological responses. Understanding the intricacies of natural biological programming offers insights into how cells and tissues self-organize, adapt, and repair, with a perspective toward advances in regenerative medicine, disease prevention, and therapeutic innovation. A better understanding of these intrinsic programming mechanisms may, in the future, enable novel biomedical applications.&lt;/p&gt;&lt;p&gt;&lt;i&gt;Foetal metabolic programming&lt;/i&gt; and &lt;i&gt;metabolic maturation&lt;/i&gt; are interconnected processes that shape an individual's metabolic health from early development through adulthood.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;&lt;i&gt;Foetal metabolic programming&lt;/i&gt;, a critical concept in developmental biology, examines how environmental factors during pregnancy influence the long-term health and disease susceptibility of the offspring.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; This field investigates the mechanisms by which prenatal exposures, such as nutrition, stress, and toxins, can alter foetal development,&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; potentially leading to chronic conditions such as obesity, diabetes, and cardiovascular disease later in life.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; Gestational diabetes mellitus is an acquired glucose intolerance with onset or first detection during pregnancy. It affects up to a fifth of all pregnant women and usually disappears after delivery.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; Foetal exposure to maternal gestational diabetes increases the risk of a multitude of adverse health outcomes for both mother and child, and is probably modified by maternal body weight. Therefore, improving glucose and weight control during pregnancy or before conception could reduce the risk to the offspring.&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; Weight control during pregnancy is mostly relevant for women who either are obese when they get pregnant, or who gain weight too quickly during pregnancy. While a pregnant woman should not go on a diet or try to lose weight during pregnancy, a focus on healthy nutrition and physical activity is helpful. Data indicate that obese women before pregnancy may benefit from recommendations regarding, for example, time-restricted eating&lt;span&gt;&lt;sup&gt;7, 8&lt;/sup&gt;&lt;/span&gt; and avoiding specific obesogenic habits such as late-night snacking&lt;span&gt;&lt;sup&gt;9&lt;/sup&gt;&lt;/span&gt; or sedentary lifestyle choices.&lt;span&gt;&lt;sup&gt;10&lt;/sup&gt;&lt;/span&gt; As current data also indicate a differential benefit of exercise for weight control at specific times during the day&lt;span&gt;&lt;sup&gt;11&lt;/sup&gt;&lt;/span&gt; and an influence of exercise-induced organ crosstalk on energy metabolism,&lt;span&gt;&lt;sup&gt;12&lt;/sup&gt;&lt;/span&gt; more data are needed to give specific recommendations for tailoring lifestyle interventions to the needs of this specific demographic. Understanding foetal programming and its im","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 10","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14207","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141615350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gender-based differences in gamification and mobile learning","authors":"Celia Piquer-Martinez,&nbsp;Maria Isabel Valverde-Merino,&nbsp;Manuel Gomez-Guzman,&nbsp;Maria Jose Zarzuelo","doi":"10.1111/apha.14206","DOIUrl":"10.1111/apha.14206","url":null,"abstract":"&lt;p&gt;Education in health careers is changing drastically aligning itself with a more patient-oriented approach.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; The use of valid and reliable instruments to assess these new skills, such as communication or ability to think critically, essentially ensures the quality of emerging professionals. Gamification has emerged as an innovative approach to enhance learning experiences by integrating game mechanics into educational settings. By incorporating rules, competition, conflict, challenge and storytelling, gamification creates an engaging and immersive environment for learners.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt;\u0000 &lt;/p&gt;&lt;p&gt;Within this evolving landscape, students have embraced the use of mobile applications (apps) as valuable tools for accessing educational materials, study aids, and patient-care resources. These apps empower students to engage in flexible and personalized learning experiences, allowing them to learn at their own pace and convenience.&lt;/p&gt;&lt;p&gt;It has been repeatedly demonstrated that the spatial abilities associated with success in the educational and professional fields of Science, Technology, Engineering, and Mathematics (STEM) are gendered, with males demonstrating clearly superior spatial abilities to females.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt;\u0000 &lt;/p&gt;&lt;p&gt;Despite the potential benefits, there is still a lack of research examining the impact of apps on education in health careers. Studies in university students, have observed gender differences, such as in the mediating role of the exercise environment in the relationship between exercise engagement and exercise adherence, not existing in male university students, while it does in female university students.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt;\u0000 &lt;/p&gt;&lt;p&gt;Within the context of education in health careers, the impact of mobile apps in classrooms on student satisfaction and academic performance has been a subject of several investigations. Students who utilized mobile health applications not only rated themselves favorably but also felt better prepared to collaborate with individuals from other disciplines compared to their peers who did not use such apps. Alhaddad in 2018 reported that students who engaged with a mobile app for drug calculation practice experienced significant enhancements in their performance relative to counterparts relying on conventional paper-based methods.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; Most recently, in 2022, Fathelrahman et al. demonstrated that students who accessed course materials and quizzes via a mobile app expressed greater satisfaction with their learning experience than those who did not utilize such technological tools.&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt;\u0000 &lt;/p&gt;&lt;p&gt;Male students showed greater improvement in learning outcomes compared to female students. This is somewhat surprising given previous research on gender differences in learning styles and preferences. The inclusion of gamification features seems to have the potential to increase us","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14206","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141578331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiovascular toxicities by calcineurin inhibitors: Cellular mechanisms behind clinical manifestations","authors":"Tanawat Attachaipanich,&nbsp;Siriporn C. Chattipakorn,&nbsp;Nipon Chattipakorn","doi":"10.1111/apha.14199","DOIUrl":"10.1111/apha.14199","url":null,"abstract":"<p>Calcineurin inhibitors (CNI), including cyclosporine A (CsA) and tacrolimus (TAC), are cornerstones of immunosuppressive therapy in solid organ transplant recipients. While extensively recognized for their capacity to induce nephrotoxicity, hypertension, and dyslipidemia, emerging reports suggest potential direct cardiovascular toxicities associated with CNI. Evidence from both in vitro and in vivo studies has demonstrated direct cardiotoxic impact of CNI, manifesting itself as induction of cardiomyocyte apoptosis, enhanced oxidative stress, inflammatory cell infiltration, and cardiac fibrosis. CNI enhances cellular apoptosis through CaSR via activation of the p38 MAPK pathway and deactivation of the ERK pathway, and enhancement of miR-377 axis. Although CNI could attenuate cardiac hypertrophy in certain animal models, CNI concurrently impaired systolic function, enhanced cardiac fibrosis, and increased the risk of heart failure. Evidence from in vivo studies demonstrated that CNI prolong the duration of action potentials through a decrease in potassium current. CNI also exerted direct effects on endothelial cell injury, inducing apoptosis and enhancing oxidative stress. CNI may induce vascular inflammation through TLR4 via MyD88 and TRIF pathways. In addition, CNI affects vascular function by impairing endothelial-dependent vasodilation and promoting vasoconstriction. Clinical studies in transplant patients also revealed an increased incidence of cardiac remodeling. However, the evidence is constrained by the limited number of participants and potential confounding factors. Several studies indicate differing cardiovascular toxicity profiles between CsA and TAC, and these could be potentially due to their different interactions with calcineurin subunits and calcineurin-independent effects. Further studies are needed to clarify these mechanisms to improve cardiovascular outcomes for transplant patients with CNI.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serotonergic input from the dorsal raphe nucleus shapes learning-associated odor responses in the olfactory bulb","authors":"Siqi Jing,&nbsp;Chi Geng,&nbsp;Penglai Liu,&nbsp;Dejuan Wang,&nbsp;Qun Li,&nbsp;Anan Li","doi":"10.1111/apha.14198","DOIUrl":"10.1111/apha.14198","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Neural activity in the olfactory bulb (OB) can represent odor information during different brain and behavioral states. For example, the odor responses of mitral/tufted (M/T) cells in the OB change during learning of odor-discrimination tasks and, at the network level, beta power increases and the high gamma (HG) power decreases during odor presentation in such tasks. However, the neural mechanisms underlying these observations remain poorly understood. Here, we investigate whether serotonergic modulation from the dorsal raphe nucleus (DRN) to the OB is involved in shaping activity during the learning process in a go/no-go task in mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Fiber photometry was used to record the population activity of DRN serotonergic neurons during a go/no-go task. In vivo electrophysiology was used to record neural activity (single units and local field potentials) in the OB during the go/no-go task. Real-time place preference (RTPP) and intracranial light administration in a specific subarea (iClass) tests were used to assess the ability of mice to encoding reward information.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Odor-evoked population activity in serotonergic neurons in the DRN was shaped during the learning process in a go/no-go task. In the OB, neural activity from oscillations to single cells showed complex, learning-associated changes and ability to encode information during an odor discrimination task. However, these properties were not observed after ablation of DRN serotonergic neurons.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The activity of neural networks and single cells in the OB, and their ability to encode information about odor value, are shaped by serotonergic projections from the DRN.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141490085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evidence for direct CO2-mediated alterations in cerebral oxidative metabolism in humans","authors":"Hannah G. Caldwell,&nbsp;Ryan L. Hoiland,&nbsp;Anthony R. Bain,&nbsp;Connor A. Howe,&nbsp;Jay M. J. R. Carr,&nbsp;Travis D. Gibbons,&nbsp;Cody G. Durrer,&nbsp;Michael M. Tymko,&nbsp;Benjamin S. Stacey,&nbsp;Damian M. Bailey,&nbsp;Mypinder S. Sekhon,&nbsp;David B. MacLeod,&nbsp;Philip N. Ainslie","doi":"10.1111/apha.14197","DOIUrl":"10.1111/apha.14197","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>How the cerebral metabolic rates of oxygen and glucose utilization (CMRO₂ and CMR_Glc, respectively) are affected by alterations in arterial PCO₂ (PaCO₂) is equivocal and therefore was the primary question of this study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective analysis involved pooled data from four separate studies, involving 41 healthy adults (35 males/6 females). Participants completed stepwise steady-state alterations in PaCO₂ ranging between 30 and 60 mmHg. The CMRO₂ and CMR_Glc were assessed via the Fick approach (CBF × arterial-internal jugular venous difference of oxygen or glucose content, respectively) utilizing duplex ultrasound of the internal carotid artery and vertebral artery to calculate cerebral blood flow (CBF).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The CMRO₂ was altered by 0.5 mL × min⁻¹ (95% CI: −0.6 to −0.3) per mmHg change in PaCO₂ (<i>p</i> &lt; 0.001) which corresponded to a 9.8% (95% CI: −13.2 to −6.5) change in CMRO₂ with a 9 mmHg change in PaCO₂ (inclusive of hypo- and hypercapnia). The CMR_Glc was reduced by 7.7% (95% CI: −15.4 to −0.08, <i>p</i> = 0.045; i.e., reduction in net glucose uptake) and the oxidative glucose index (ratio of oxygen to glucose uptake) was reduced by 5.6% (95% CI: −11.2 to 0.06, <i>p</i> = 0.049) with a + 9 mmHg increase in PaCO₂.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Collectively, the CMRO₂ is altered by approximately 1% per mmHg change in PaCO₂. Further, glucose is incompletely oxidized during hypercapnia, indicating reductions in CMRO₂ are either met by compensatory increases in nonoxidative glucose metabolism or explained by a reduction in total energy production.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14197","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141490083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Indices of human heat stress in times of climate change","authors":"Shane K. Maloney,&nbsp;Michael R. Kearney,&nbsp;Duncan Mitchell","doi":"10.1111/apha.14196","DOIUrl":"10.1111/apha.14196","url":null,"abstract":"&lt;p&gt;Body temperature is one of the cardinal regulated variables in human physiology, along with blood gasses, pH, and osmolality. Pathological deviations of body temperature from normal, some potentially lethal, are becoming more likely with climate change. Sherwood and Huber&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; famously used a critical wet-bulb temperature that would cause pathology to project areas of the world that would become uninhabitable in a climate-changed future. Many other indices that incorporate the wet-bulb temperature have been advanced to predict human heat stress. As pointed out by Maloney,&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; and recently confirmed empirically,&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; those indices underestimate the impact of climate change on human thermoregulation, especially at lower humidity when physiological, rather than environmental, factors limit evaporative cooling (Figure 1).&lt;/p&gt;&lt;p&gt;Because the human body exchanges heat with the environment by four routes (conduction, convection, radiation, and evaporation), each impacted by different environmental variables, no single number can quantify that heat exchange accurately.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; But single numbers have nevertheless been proposed as indices of human heat stress. Because the dry-bulb temperature was poor at predicting the thermoregulatory responses of humans to different environments, in 1905 the English physiologist John Scott Haldane proposed the wet-bulb temperature as an alternative. The wet-bulb temperature is measured by placing a wetted sleeve over the bulb of a normal thermometer. Evaporation from the sleeve lowers the reading on the thermometer; the lower the humidity, the lower the reading of the wet-bulb thermometer below that of the normal thermometer. Wet-bulb temperature has been incorporated in many of the more than 150 indices of human thermal stress that have been developed over the past century.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; As well as underestimating the likelihood of pathology in some conditions, many of those indices also ignore the impact of air movement on both human heat exchange and on the wet-bulb temperature.&lt;/p&gt;&lt;p&gt;We all have been comforted by a breeze on a hot day, if we have been sweating. That effect has been quantified for acclimated women walking on a treadmill by measuring the upper limits of the prescriptive zone (ULPZ; that range of conditions in which core body temperature is affected by the level of metabolic heat production but not by the environment). In still air, the women could achieve heat balance in the conditions indicated by red shading below the dotted line in Figure 1. Conditions above that dotted line were above ULPZ, and the women became hyperthermic. At 1 ms&lt;sup&gt;−1&lt;/sup&gt; of forced air movement, their ULPZ increased to include the conditions indicated by dark-yellow shading below the solid line in Figure 1, so the ability of those women to avoid pathology improved. That improvement would not have been predicted by an index based on we","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14196","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141490084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multigenerational exposure to temperature influences mitochondrial oxygen fluxes in the Medaka fish (Oryzias latipes)","authors":"Julie Morla,&nbsp;Karine Salin,&nbsp;Rémy Lassus,&nbsp;Julie Favre-Marinet,&nbsp;Arnaud Sentis,&nbsp;Martin Daufresne","doi":"10.1111/apha.14194","DOIUrl":"10.1111/apha.14194","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Thermal sensitivity of cellular metabolism is crucial for animal physiology and survival under climate change. Despite recent efforts, effects of multigenerational exposure to temperature on the metabolic functioning remain poorly understood. We aimed at determining whether multigenerational exposure to temperature modulate the mitochondrial respiratory response of Medaka fish.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a multigenerational exposure with Medaka fish reared multiple generations at 20 and 30°C (COLD and WARM fish, respectively). We then measured the oxygen consumption of tail muscle at two assay temperatures (20 and 30°C). Mitochondrial function was determined as the respiration supporting ATP synthesis (OXPHOS) and the respiration required to offset proton leak (LEAK(Omy)) in a full factorial design (COLD-20°C; COLD-30°C; WARM-20°C; WARM-30°C).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that higher OXPHOS and LEAK fluxes at 30°C compared to 20°C assay temperature. At each assay temperature, WARM fish had lower tissue oxygen fluxes than COLD fish. Interestingly, we did not find significant differences in respiratory flux when mitochondria were assessed at the rearing temperature of the fish (i.e., COLD-20°C vs. WARM −30°C).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The lower OXPHOS and LEAK capacities in warm fish are likely the result of the multigenerational exposure to warm temperature. This is consistent with a modulatory response of mitochondrial capacity to compensate for potential detrimental effects of warming on metabolism. Finally, the absence of significant differences in respiratory fluxes between COLD-20°C and WARM-30°C fish likely reflects an optimal respiration flux when organisms adapt to their thermal conditions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 8","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141453792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}