American journal of physiology. Regulatory, integrative and comparative physiology最新文献

{"title":"Adipose biopsy techniques for studies in human exercise physiology.","authors":"Colleen E Lynch, Anna R Brandt, Caroline S Vincenty, Ethan Robbins, Chad Skiles, Kiril Minchev, Toby L Chambers, Alicia Belangee, Todd A Trappe, Scott W Trappe","doi":"10.1152/ajpregu.00266.2023","DOIUrl":"10.1152/ajpregu.00266.2023","url":null,"abstract":"<p><p>Adipose biopsy techniques are relatively undefined for exercise physiology research in individuals at or near normal weight. The purpose of this study was to compare the influence of two adipose biopsy techniques on tissue quality through measurements of adipocyte cell size, as well as mRNA and protein levels of select pro- and anti-inflammatory cytokines and adipokines. Thirteen participants (9 M, 4 W; 28 ± 4 yr; 27 ± 3 kg·m^-2; V̇o_2max: 3.3 ± 0.7 L·min^-1) underwent subcutaneous adipose biopsies on either side of the umbilicus (incision: ∼8 cm lateral, sampling area: ∼5 cm lateral) using <i>1</i>) a 6-mm Bergström biopsy needle and <i>2</i>) a mini-liposuction approach with a 4-mm Mercedes biopsy needle that used prebiopsy tumescent delivery (∼30 mL 0.9% NaCl solution) into the sampling area (i.e., 'wet' technique). Tissue obtained was processed identically for analysis and both techniques returned high-quality tissue for histology (similar % intact adipocytes), mRNA (RNA integrity numbers >7.0), and protein. Adipocyte size was similar (<i>P</i> > 0.05) between both techniques (Bergström: 6,116 ± 1,652 μm², 554-23,522 µm²; Mercedes: 6,517 ± 952 μm², 926-21,969 µm²). There were also no differences (<i>P</i> > 0.05) between the two techniques for the measured cytokines (pro- and anti-inflammatory) and adipokines at the mRNA and protein levels. Adipocyte size was positively correlated with body mass index and body fat percentage, and negatively correlated with V̇o_2max (<i>P</i> < 0.05). These results suggest both adipose biopsy techniques used in the current investigation are appropriate for histological, transcriptional, and translational level measurements in exercise physiology studies of nonobese women and men.<b>NEW & NOTEWORTHY</b> This study provides investigators with useful information related to adipose biopsy sampling approaches that can be used when planning studies that use measurements of adipose histology, as well as measurements at the mRNA and protein level. Adipose periumbilical sampling with the Bergström biopsy needle and the Mercedes wet mini-liposuction technique are both appropriate options for studies in exercise physiology and in nonobese individuals.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R220-R229"},"PeriodicalIF":2.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139465519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Short-term dynamic characteristics of diuresis during exogenous pressure perturbations with and without arterial baroreflex control.","authors":"Toru Kawada, Hiroki Matsushita, Shohei Yokota, Yuki Yoshida, Masafumi Fukumitsu, Joe Alexander, Keita Saku","doi":"10.1152/ajpregu.00229.2023","DOIUrl":"10.1152/ajpregu.00229.2023","url":null,"abstract":"<p><p>Although body fluid volume control by the kidneys may be classified as a long-term arterial pressure (AP) control system, it does not necessarily follow that the urine flow (UF) response to changes in AP is slow. We quantified the dynamic characteristics of the UF response to short-term AP changes by changing mean AP between 60 mmHg and 100 mmHg every 10 s according to a binary white noise sequence in anesthetized rats (<i>n</i> = 8 animals). In a baro-on trial (the carotid sinus baroreflex was enabled), the UF response represented the combined synergistic effects of pressure diuresis (PD) and neurally mediated antidiuresis (NMA). In a baro-fix trial (the carotid sinus pressure was fixed at 100 mmHg), the UF response mainly reflected the effect of PD. The UF step response was quantified using the sum of two exponential decay functions. The fast and slow components had time constants of 6.5 ± 3.6 s and 102 ± 85 s (means ± SD), respectively, in the baro-on trial. Although the gain of the fast component did not differ between the two trials (0.49 ± 0.21 vs. 0.66 ± 0.22 µL·min^-1·kg^-1·mmHg^-1), the gain of the slow component was greater in the baro-on than in the baro-fix trial (0.51 ± 0.14 vs. 0.09 ± 0.39 µL·min^-1·kg^-1·mmHg^-1, <i>P</i> = 0.023). The magnitude of NMA relative to PD was calculated to be 32.2 ± 29.8%. In conclusion, NMA contributed to the slow component, and its magnitude was approximately one-third of that of the effect of PD.<b>NEW & NOTEWORTHY</b> We quantified short-term dynamic characteristics of the urine flow (UF) response to arterial pressure (AP) changes using white noise analysis. The UF step response approximated the sum of two exponential decay functions with time constants of ∼6.5 s and 102 s. The neurally mediated antidiuretic (NMA) effect contributed to the slow component of the UF step response, with the magnitude of approximately one-third of that of the pressure diuresis (PD) effect.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R230-R241"},"PeriodicalIF":2.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139465520","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":"Effects of hyperventilation on repeated breath-holding while in a fasting state: do risks outweigh the benefits?","authors":"Antonis Elia, Mikael Gennser, Ola Eiken, Michail E. Keramidas","doi":"10.1152/ajpregu.00260.2023","DOIUrl":"https://doi.org/10.1152/ajpregu.00260.2023","url":null,"abstract":"American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, Ahead of Print. <br/>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":"8 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139689192","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":"Senescent hearts from male Ts65Dn mice exhibit preserved function but altered size and nicotinamide adenine dinucleotide pathway signaling.","authors":"Josef Brandauer, Candace N Receno, Cynthia Anyaoku, Lauren E Cooke, Hannalyn M Schwarzer, Keith C DeRuisseau, Caitlin M Cunningham, Lara R DeRuisseau","doi":"10.1152/ajpregu.00164.2023","DOIUrl":"10.1152/ajpregu.00164.2023","url":null,"abstract":"<p><p>Down syndrome (DS) is associated with congenital heart defects at birth, but cardiac function has not been assessed at older ages. We used the Ts65Dn mouse, a model of DS, to quantify heart structure and function with echocardiography in 18-mo male Ts65Dn and wild-type (WT) mice. Heart weight, nicotinamide adenine dinucleotide (NAD) signaling, and mitochondrial (citrate synthase) activity were investigated, as these pathways may be implicated in the cardiac pathology of DS. The left ventricle was smaller in Ts65Dn versus WT, as well as the anterior wall thickness of the left ventricle during both diastole (LVAW_d; mm) and systole (LVAW_s; mm) as assessed by echocardiography. Other functional metrics were similar between groups including left ventricular area end systole (mm²), left ventricular area end diastole (mm²), left ventricular diameter end systole (mm), left ventricular diameter end diastole (mm), isovolumetric relaxation time (ms), mitral valve atrial peak velocity (mm/s), mitral valve early peak velocity (mm/s), ratio of atrial and early peak velocities (E/A), heart rate (beats/min), ejection fraction (%), and fractional shortening (%). Nicotinamide phosphoribosyltransferase (NAMPT) protein expression, NAD concentration, and tissue weight were lower in the left ventricle of Ts65Dn versus WT mice. Sirtuin 3 (SIRT3) protein expression and citrate synthase activity were not different between groups. Although cardiac function was generally preserved in male Ts65Dn, the altered heart size and bioenergetic disturbances may contribute to differences in aging for DS.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R176-R183"},"PeriodicalIF":2.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11283890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138476618","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":"Exertional heat stroke causes long-term skeletal muscle epigenetic reprogramming, altered gene expression, and impaired satellite cell function in mice.","authors":"Kevin O Murray, Jason O Brant, Ray A Spradlin, Trace Thome, Orlando Laitano, Terence E Ryan, Alberto Riva, Michael P Kladde, Thomas L Clanton","doi":"10.1152/ajpregu.00226.2023","DOIUrl":"10.1152/ajpregu.00226.2023","url":null,"abstract":"<p><p>The effect of exertional heat stroke (EHS) exposure on skeletal muscles is incompletely understood. Muscle weakness is an early symptom of EHS but is not considered a major target of multiorgan injury. Previously, in a preclinical mouse model of EHS, we observed the vulnerability of limb muscles to a second EHS exposure, suggesting hidden processes contributing to declines in muscle resilience. Here, we evaluated the possible molecular origins of EHS-induced declines in muscle resilience. Female C57BL/6 mice [total <i>n</i> = 56; 28/condition, i.e., EHS and exercise control (EXC)] underwent forced wheel running at 37.5°C/40% relative humidity until symptom limitation (unconsciousness). EXC mice exercised identically at room temperature (22-23°C). After 1 mo of recovery, the following were assessed: <i>1</i>) specific force and caffeine-induced contracture in soleus (SOL) and extensor digitorum longus (EDL) muscles; <i>2</i>) transcriptome and DNA methylome responses in gastrocnemius (GAST); and <i>3</i>) primary satellite cell function (proliferation and differentiation). There were no differences in specific force in either SOL or EDL from EXC. Only EHS solei exhibited lower caffeine sensitivity. EHS GAST exhibited higher RNA expression of genes encoding structural proteins of slow fibers, heat shock proteins, and myogenesis. A total of ∼2,500 differentially methylated regions of DNA that could potentially affect many cell functions were identified. Primary satellite cells exhibited suppressed proliferation rates but normal differentiation responses. Results demonstrate long-term changes in skeletal muscles 1 mo after EHS that could contribute to declines in muscle resilience. Skeletal muscle may join other, more recognized tissues considered vulnerable to long-term effects of EHS.<b>NEW & NOTEWORTHY</b> Exertional heat stroke (EHS) in mice induces long-term molecular and functional changes in limb muscle that could reflect a loss of \"resilience\" to further stress. The phenotype was characterized by altered caffeine sensitivity and suppressed satellite cell proliferative potential. This was accompanied by changes in gene expression and DNA methylation consistent with ongoing muscle remodeling and stress adaptation. We propose that EHS may induce a prolonged vulnerability of skeletal muscle to further stress or injury.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R160-R175"},"PeriodicalIF":2.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11283893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138476615","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":"Intermittent normobaric hypoxia alters substrate partitioning and muscle oxygenation in individuals with obesity: implications for fat burning.","authors":"Guillaume Costalat, Frederic Lemaitre, Sandra Ramos, Gillian M C Renshaw","doi":"10.1152/ajpregu.00153.2023","DOIUrl":"10.1152/ajpregu.00153.2023","url":null,"abstract":"<p><p>This single-blind, crossover study aimed to measure and evaluate the short-term metabolic responses to continuous and intermittent hypoxic patterns in individuals with obesity. Indirect calorimetry was used to quantify changes in resting metabolic rate (RMR), carbohydrate (CHO_ox, %CHO), and fat oxidation (FAT_ox, %FAT) in nine individuals with obesity pre and post: <i>1</i>) breathing normoxic air [normoxic sham control (NS-control)], <i>2</i>) breathing continuous hypoxia (CH), or <i>3</i>) breathing intermittent hypoxia (IH). A mean peripheral oxygen saturation ([Formula: see text]) of 80-85% was achieved over a total of 45 min of hypoxia. Throughout each intervention, pulmonary gas exchanges, oxygen consumption (V̇o₂) carbon dioxide production (V̇co₂), and deoxyhemoglobin concentration (Δ[HHb]) in the vastus lateralis were measured. Both RMR and CHO_ox measured pre- and postinterventions were unchanged following each treatment: NS-control, CH, or IH (all <i>P</i> > 0.05). Conversely, a significant increase in FAT_ox was evident between pre- and post-IH (+44%, <i>P</i> = 0.048). Although the mean Δ[HHb] values significantly increased during both IH and CH (<i>P</i> < 0.05), the greatest zenith of Δ[HHb] was achieved in IH compared with CH (<i>P</i> = 0.002). Furthermore, there was a positive correlation between Δ[HHb] and the shift in FAT_ox measured pre- and postintervention. It is suggested that during IH, the increased bouts of muscle hypoxia, revealed by elevated Δ[HHb], coupled with cyclic periods of excess posthypoxia oxygen consumption (EPHOC, inherent to the intermittent pattern) played a significant role in driving the increase in FAT_ox post-IH.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R147-R159"},"PeriodicalIF":2.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138476617","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":"Expression of prolyl hydroxylase domains, the upstream regulators of HIF, in the brain of the anoxia-tolerant crucian carp during anoxia-reoxygenation.","authors":"Lucie Gerber, Julien Resseguier, Tellef Helle-Valle, Elie Farhat, Göran E Nilsson, Sjannie Lefevre","doi":"10.1152/ajpregu.00211.2023","DOIUrl":"10.1152/ajpregu.00211.2023","url":null,"abstract":"<p><p>The hypoxia-inducible factor (HIF) is considered key in the transcriptional response to low oxygen. Yet, the role of HIF in the absence of oxygen (anoxia) and in preparation for reoxygenation remains unclear. Recent studies suggest that mounting a HIF response may be counterproductive for anoxia survival. We here studied one of the champions of anoxia survival, the crucian carp (<i>Carassius carassius</i>), and hypothesized that expression of prolyl hydroxylase domains (PHDs; the upstream regulators of HIF) are upregulated to circumvent an energy-costly activation of HIF in anoxia and to prepare for reoxygenation. We measured whole brain mRNA and protein levels of the three isoforms PHD1, PHD2, and PHD3, coded for by multiple paralogs of the genes <i>egln2</i>, <i>egln1</i>, and <i>egln3</i>, using quantitative PCR and Western blotting in the brain of crucian carps exposed to 5 days normoxia or anoxia, and 5 days anoxia followed by 3 or 24 h of reoxygenation. The mRNA levels of most <i>egln</i> paralogs were increased in anoxia and upon reoxygenation, with <i>egln3</i> showing the largest increase in mRNA level (up to 17-fold) and highest relative mRNA abundance (up to 75% of expressed <i>egln</i>). The protein level of all PHDs was maintained in anoxia and increased upon reoxygenation. We then explored PHD distribution in different brain regions and found PHD immunoreactivity to be associated with axonal branches and showing region-specific changes during anoxia-reoxygenation. Our results support an overall upregulation of <i>egln</i> under prolonged anoxia and PHDs upon reoxygenation in crucian carp, likely aimed at suppressing HIF responses, although regional differences are apparent in such a complex organ as the brain.<b>NEW & NOTEWORTHY</b> We report a profound upregulation of most <i>egln</i> paralog mRNA levels in anoxia and upon reoxygenation, with <i>egln3ii</i> showing the largest, a 17-fold increase, and highest relative mRNA abundance. The relative abundance of prolyl hydroxylase domain (PHD) proteins was maintained during anoxia and increased at reoxygenation. PHD immunoreactivity was localized to axonal branches with region-specific changes during anoxia-reoxygenation. These dynamic and regional changes in crucian carp, champion of anoxia tolerance, are most likely adaptive and call for further mechanistic studies.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R184-R195"},"PeriodicalIF":2.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139032029","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":"Input-size dependence of the baroreflex neural arc transfer characteristics during Gaussian white noise inputs.","authors":"Toru Kawada, Tadayoshi Miyamoto, Masafumi Fukumitsu, Keita Saku","doi":"10.1152/ajpregu.00199.2023","DOIUrl":"10.1152/ajpregu.00199.2023","url":null,"abstract":"<p><p>Although Gaussian white noise (GWN) inputs offer a theoretical framework for identifying higher-order nonlinearity, an actual application to the data of the neural arc of the carotid sinus baroreflex did not succeed in fully predicting the well-known sigmoidal nonlinearity. In the present study, we assumed that the neural arc can be approximated by a cascade of a linear dynamic (LD) component and a nonlinear static (NS) component. We analyzed the data obtained using GWN inputs with a mean of 120 mmHg and standard deviations (SDs) of 10, 20, and 30 mmHg for 15 min each in anesthetized rats (<i>n</i> = 7). We first estimated the linear transfer function from carotid sinus pressure to sympathetic nerve activity (SNA) and then plotted the measured SNA against the linearly predicted SNA. The predicted and measured data pairs exhibited an inverse sigmoidal distribution when grouped into 10 bins based on the size of the linearly predicted SNA. The sigmoidal nonlinearity estimated via the LD-NS model showed a midpoint pressure (104.1 ± 4.4 mmHg for SD of 30 mmHg) lower than that estimated by a conventional stepwise input (135.8 ± 3.9 mmHg, <i>P</i> < 0.001). This suggests that the NS component is more likely to reflect the nonlinearity observed during pulsatile inputs that are physiological to baroreceptors. Furthermore, the LD-NS model yielded higher <i>R</i>² values compared with the linear model and the previously suggested second-order Uryson model in the testing dataset.<b>NEW & NOTEWORTHY</b> We examined the input-size dependence of the baroreflex neural arc transfer characteristics during Gaussian white noise inputs. A linear dynamic-static nonlinear model yielded higher <i>R</i>² values compared with a linear model and captured the well-known sigmoidal nonlinearity of the neural arc, indicating that the nonlinear dynamics contributed to determining sympathetic nerve activity. Ignoring such nonlinear dynamics might reduce our ability to explain underlying physiology and significantly limit the interpretation of experimental data.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R121-R133"},"PeriodicalIF":2.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138476616","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":"Differences in the range of thermoneutral zone between mouse strains: potential effects on translational research.","authors":"Andrzej K Gębczyński, Julita Sadowska, Marek Konarzewski","doi":"10.1152/ajpregu.00154.2023","DOIUrl":"10.1152/ajpregu.00154.2023","url":null,"abstract":"<p><p>Laboratory mice are commonly used for studies emulating human metabolism. To render human energetics, their ratio of daily (DEE) to basal (BMR) energy expenditure of 1.7-1.8 should be maintained. However, the DEE/BMR ratio strongly depends on whether a given study using a mouse model is carried out above, or below the lower critical temperature (LCT) of the thermoneutral zone, which is rarely considered in translational research. Here, we used mice artificially selected for high or low rates of BMR along with literature data to analyze the effect of ambient temperature on possible systematic bias in DEE/BMR. We demonstrated that the estimated LCTs of mice from the high and low BMR lines differ by more than 7°C. Furthermore, the range of variation of LCTs of mouse strains used in translational research spans from 23 to 33°C. Differences between LCTs in our selected mice and other mouse strains are mirrored by differences in their DEE-to-BMR ratio, on average increasing it at the rate of 0.172°C^-1 at temperatures below LCT. Given the wide range of LCTs in different mouse strains, we conclude that the energetic cost of thermoregulation may differ greatly for different mouse strains with a potentially large impact on translational outcomes. Thus, the LCT of a given mouse strain is an important factor that must be considered in designing translational studies.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R91-R99"},"PeriodicalIF":2.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138440196","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":"Muscle metaboreflex stimulates the cardiac sympathetic afferent reflex causing positive feedback amplification of sympathetic activity: effect of heart failure.","authors":"Joseph Mannozzi, Danielle Senador, Jasdeep Kaur, Matthew Gross, Megan McNitt, Alberto Alvarez, Beruk Lessanework, Donal S O'Leary","doi":"10.1152/ajpregu.00235.2023","DOIUrl":"10.1152/ajpregu.00235.2023","url":null,"abstract":"<p><p>Exercise intolerance is a hallmark symptom of heart failure and to a large extent stems from reductions in cardiac output that occur due to the inherent ventricular dysfunction coupled with enhanced muscle metaboreflex-induced functional coronary vasoconstriction, which limits increases in coronary blood flow. This creates a further mismatch between O₂ delivery and O₂ demand, which may activate the cardiac sympathetic afferent reflex (CSAR), causing amplification of the already increased sympathetic activity in a positive-feedback fashion. We used our chronically instrumented conscious canine model to evaluate if chronic ablation of afferents responsible for the CSAR would attenuate the gain of muscle metaboreflex before and after induction of heart failure. After afferent ablation, the gain of the muscle metaboreflex control of mean arterial pressure was significantly reduced before (-239.5 ± 16 to -95.2 ± 8 mmHg/L/min) and after the induction of heart failure (-185.6 ± 14 to -95.7 ± 12 mmHg/L/min). Similar results were observed for the strength (gain) of muscle metaboreflex control of heart rate, cardiac output, and ventricular contractility. Thus, we conclude that the CSAR contributes significantly to the strength of the muscle metaboreflex in normal animals with heart failure serving as an effective positive-feedback amplifier thereby further increasing sympathetic activity.<b>NEW & NOTEWORTHY</b> The powerful pressor responses from the CSAR arise via O₂ delivery versus O₂ demand imbalance. Muscle metaboreflex activation (MMA) simultaneously elicits coronary vasoconstriction (which is augmented in heart failure) and profound increases in cardiac work thereby upsetting oxygen balance. Whether MMA activates the CSAR thereby amplifying MMA responses is unknown. We observed that removal of the CSAR afferents attenuated the strength of the muscle metaboreflex in normal and subjects with heart failure.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R110-R120"},"PeriodicalIF":2.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11283898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138440197","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}