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Adipose biopsy techniques for studies in human exercise physiology. 用于人体运动生理学研究的脂肪活检技术。
IF 2.8 3区 医学 Q3 PHYSIOLOGY Pub Date : 2024-03-01 Epub Date: 2024-01-15 DOI: 10.1152/ajpregu.00266.2023
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

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; V̇o2max: 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 1) a 6-mm Bergström biopsy needle and 2) 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 (P > 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 (P > 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 V̇o2max (P < 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.NEW & NOTEWORTHY 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.

对于体重正常或接近正常的人的运动生理学研究来说,脂肪活检技术还相对不够明确。本研究的目的是通过测量脂肪细胞的大小以及某些促炎和抗炎细胞因子和脂肪因子的 mRNA 和蛋白质水平,比较两种脂肪活检技术对组织质量的影响。13 名参与者(9 名男性,4 名女性;28±4 岁;27±3 kg-m-2;VO2max:3.3±0.7 L-min-1)在脐部两侧进行皮下脂肪活检(切口:外侧约 8 厘米,取样区域:外侧约 5 厘米),使用 1) 6 毫米 Bergström 活检针;2) 小型抽脂法,使用 4 毫米 Mercedes 活检针,活检前向取样区域注射膨胀剂(约 30 毫升 0.9% 氯化钠溶液)(即 "湿 "技术)、湿 "技术)。获得的组织经过相同的分析处理,两种技术都能获得高质量的组织学(完整脂肪细胞的百分比相似)、mRNA(RNA 完整性大于 7.0)和蛋白质。两种技术的脂肪细胞大小相似(P>0.05)(Bergström:6116±1652 μm2,554-23522 μm2;Mercedes:6517±952 μm2,926-21969 μm2)。两种技术在测量细胞因子(促炎和抗炎)和脂肪因子的 mRNA 和蛋白质水平上也没有差异(P>0.05)。脂肪细胞的大小与体重指数和体脂率呈正相关,与最大氧饱和度呈负相关(P<0.05)。
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引用次数: 0
Short-term dynamic characteristics of diuresis during exogenous pressure perturbations with and without arterial baroreflex control. 在有和没有动脉气压反射控制的情况下,外源性压力扰动时利尿的短期动态特性。
IF 2.8 3区 医学 Q3 PHYSIOLOGY Pub Date : 2024-03-01 Epub Date: 2024-01-15 DOI: 10.1152/ajpregu.00229.2023
Toru Kawada, Hiroki Matsushita, Shohei Yokota, Yuki Yoshida, Masafumi Fukumitsu, Joe Alexander, Keita Saku

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 (n = 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, P = 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.NEW & NOTEWORTHY 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.

虽然肾脏对体液容量的控制可归类为长期动脉压(AP)控制系统,但这并不一定意味着尿流(UF)对动脉压变化的反应是缓慢的。我们通过在麻醉大鼠(n = 8)中根据二进制白噪声序列每 10 秒改变 60 mmHg 和 100 mmHg 之间的平均动脉压,量化了尿量对短期动脉压变化的动态响应特征。在气压开启试验中(颈动脉窦巴反射被激活),UF 反应代表了压力利尿(PD)和神经介导的抗利尿(NMA)的综合协同效应。在气压固定试验中(颈动脉窦压力固定在 100 毫米汞柱),超滤反应主要反映了压力利尿的效果。使用两个指数衰减函数之和对 UF 阶跃响应进行量化。在气压开启试验中,快速和慢速分量的时间常数分别为 6.5±3.6 秒和 102±85 秒(平均值±标度)。虽然快速分量的增益在两次试验中没有差异(0.49 ± 0.21 vs. 0.66 ± 0.22 mL-min-1-kg-1-mmHg-1),但慢速分量的增益在 baro-on 试验中大于 baro-fix 试验(0.51 ± 0.14 vs. 0.09 ± 0.39 mL-min-1-kg-1-mmHg-1,P = 0.023)。经计算,NMA 相对于 PD 的比例为 32.2 ± 29.8%。总之,NMA 对慢速成分有影响,其影响程度约为 PD 影响的三分之一。
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引用次数: 0
Effects of hyperventilation on repeated breath-holding while in a fasting state: do risks outweigh the benefits? 空腹状态下过度换气对反复憋气的影响:风险是否大于收益?
IF 2.8 3区 医学 Q3 PHYSIOLOGY Pub Date : 2024-02-05 DOI: 10.1152/ajpregu.00260.2023
Antonis Elia, Mikael Gennser, Ola Eiken, Michail E. Keramidas
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, Ahead of Print.
美国生理学杂志-调节、综合和比较生理学》,提前出版。
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引用次数: 0
Senescent hearts from male Ts65Dn mice exhibit preserved function but altered size and nicotinamide adenine dinucleotide pathway signaling. 雄性Ts65Dn小鼠衰老后的心脏功能保留,但大小和烟酰胺腺嘌呤二核苷酸信号通路发生改变。
IF 2.2 3区 医学 Q3 PHYSIOLOGY Pub Date : 2024-02-01 Epub Date: 2023-12-04 DOI: 10.1152/ajpregu.00164.2023
Josef Brandauer, Candace N Receno, Cynthia Anyaoku, Lauren E Cooke, Hannalyn M Schwarzer, Keith C DeRuisseau, Caitlin M Cunningham, Lara R DeRuisseau

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.

唐氏综合征(Ds)与出生时的先天性心脏缺陷有关,但老年时的心脏功能尚未得到评估。我们使用Ds模型Ts65Dn小鼠,用超声心动图量化18月龄雄性Ts65Dn小鼠和WT小鼠的心脏结构和功能。我们研究了心脏重量、烟酰胺腺嘌呤二核苷酸(NAD)信号和线粒体(柠檬酸合成酶)活性,因为这些途径可能与Ds的心脏病理有关。与WT相比,Ts65Dn组左心室体积更小,两次舒张期左心室前壁厚度(LVAW_d;mm)和收缩期(LVAW_s;Mm),超声心动图评估。其他功能指标组间相似,包括左室收缩期末期面积(mm2)、左室舒张末期面积(mm2)、左室收缩期末期直径(mm)、左室舒张末期直径(mm)、等容松弛时间(ms)、二尖瓣心房峰值速度(mm/s)、二尖瓣早期峰值速度(mm/s)、心房与早期峰值速度之比(E/A)、心率(bpm)、射血分数(%)和缩短分数(%)。与WT小鼠相比,Ts65Dn小鼠左心室烟酰胺磷酸核糖基转移酶(NAMPT)蛋白表达、NAD浓度和组织重量均较低。各组间Sirtuin 3 (SIRT3)蛋白表达及柠檬酸合成酶活性无显著差异。虽然男性Ts65Dn患者的心脏功能一般保持不变,但心脏大小的改变和生物能量紊乱可能导致Ds患者的衰老差异。
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引用次数: 0
Exertional heat stroke causes long-term skeletal muscle epigenetic reprogramming, altered gene expression, and impaired satellite cell function in mice. 劳累性中暑导致小鼠骨骼肌长期表观遗传重编程、基因表达改变和卫星细胞功能受损。
IF 2.2 3区 医学 Q3 PHYSIOLOGY Pub Date : 2024-02-01 Epub Date: 2023-12-04 DOI: 10.1152/ajpregu.00226.2023
Kevin O Murray, Jason O Brant, Ray A Spradlin, Trace Thome, Orlando Laitano, Terence E Ryan, Alberto Riva, Michael P Kladde, Thomas L Clanton

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 n = 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: 1) specific force and caffeine-induced contracture in soleus (SOL) and extensor digitorum longus (EDL) muscles; 2) transcriptome and DNA methylome responses in gastrocnemius (GAST); and 3) 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.NEW & NOTEWORTHY 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.

劳累性中暑(EHS)暴露对骨骼肌的影响尚不完全清楚。肌肉无力是EHS的早期症状,但不被认为是多器官损伤的主要目标。此前,在EHS的临床前小鼠模型中,我们观察到肢体肌肉对第二次EHS暴露的易感性,这表明隐藏的过程导致了肌肉恢复能力的下降。在这里,我们评估了ehs诱导的肌肉恢复力下降的可能分子起源。雌性C57BL/6小鼠[总n =56;28/条件,即EHS和运动控制(EXC)]在37.5°C/40%相对湿度下进行强制车轮运行,直到症状限制(无意识)。EXC小鼠在室温(22-23℃)下运动相同。恢复一个月后,进行以下评估:(1)比目鱼肌(SOL)和指长伸肌(EDL)肌肉的比力和咖啡因引起的挛缩;(2)腓肠肌(GAST)的转录组和DNA甲基组反应;(3)初级卫星细胞功能(增殖和分化)。与EXC相比,SOL和EDL的比力没有差异,只有EHS solei对咖啡因的敏感性较低。EHS GAST表现出较高的慢纤维结构蛋白、热休克蛋白和肌生成基因的RNA表达。总共鉴定了约2500个可能影响许多细胞功能的DNA差异甲基化区域。原代卫星细胞增殖速率受到抑制,但分化反应正常。结果表明,EHS后一个月骨骼肌的长期变化可能导致肌肉弹性下降。骨骼肌可能会加入其他更容易受到EHS长期影响的组织。
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引用次数: 0
Intermittent normobaric hypoxia alters substrate partitioning and muscle oxygenation in individuals with obesity: implications for fat burning. 间歇性常压缺氧改变肥胖个体的底物分配和肌肉氧合:对脂肪燃烧的影响。
IF 2.8 3区 医学 Q3 PHYSIOLOGY Pub Date : 2024-02-01 Epub Date: 2023-12-04 DOI: 10.1152/ajpregu.00153.2023
Guillaume Costalat, Frederic Lemaitre, Sandra Ramos, Gillian M C Renshaw

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 (CHOox, %CHO), and fat oxidation (FATox, %FAT) in nine individuals with obesity pre and post: 1) breathing normoxic air [normoxic sham control (NS-control)], 2) breathing continuous hypoxia (CH), or 3) 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 CHOox measured pre- and postinterventions were unchanged following each treatment: NS-control, CH, or IH (all P > 0.05). Conversely, a significant increase in FATox was evident between pre- and post-IH (+44%, P = 0.048). Although the mean Δ[HHb] values significantly increased during both IH and CH (P < 0.05), the greatest zenith of Δ[HHb] was achieved in IH compared with CH (P = 0.002). Furthermore, there was a positive correlation between Δ[HHb] and the shift in FATox 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 FATox post-IH.

这项单盲交叉研究旨在测量和评估肥胖患者对持续和间歇性缺氧模式的短期代谢反应。采用间接量热法量化9例肥胖患者静息代谢率(RMR)、碳水化合物(chox, %CHO)和脂肪氧化(FATox, % fat)在以下前后的变化:(i)呼吸常压空气[常压假对照(NS-control)];(ii)呼吸持续缺氧(CH);或(iii)间歇性缺氧(IH)。在45分钟的缺氧时间内,平均外周氧饱和度(SpO2)达到80-85%。在每次干预过程中,测量肺气体交换——耗氧量()、二氧化碳产生()和股外侧肌脱氧血红蛋白浓度([hbb])。每次治疗后,干预前和干预后的RMR和chox测量结果都没有变化:CH;或IH(均p > 0.05)。相反,在ih前后,FATox显著增加(+44%,p = 0.048)。虽然平均[hbb]值在IH和CH期间显著增加(p),但与CH相比,IH达到了[hbb]的最大顶点(p = 0.002)。此外,干预前后测得的FATox变化与∆[hbb]呈正相关。这表明,在IH期间,肌肉缺氧次数的增加(表现为升高的∆[hbb]),加上缺氧后过量氧气消耗的循环周期(EPHOC,固有的间歇性模式)在推动IH后FATox的增加中发挥了重要作用。
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引用次数: 0
Expression of prolyl hydroxylase domains, the upstream regulators of HIF, in the brain of the anoxia-tolerant crucian carp during anoxia-reoxygenation. 耐缺氧鲫鱼脑部在缺氧-再氧合过程中脯氨酰羟化酶域(PHDs)(HIF 的上游调节因子)的表达。
IF 2.8 3区 医学 Q3 PHYSIOLOGY Pub Date : 2024-02-01 Epub Date: 2023-12-25 DOI: 10.1152/ajpregu.00211.2023
Lucie Gerber, Julien Resseguier, Tellef Helle-Valle, Elie Farhat, Göran E Nilsson, Sjannie Lefevre

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 (Carassius carassius), 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 egln2, egln1, and egln3, 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 egln paralogs were increased in anoxia and upon reoxygenation, with egln3 showing the largest increase in mRNA level (up to 17-fold) and highest relative mRNA abundance (up to 75% of expressed egln). 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 egln 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.NEW & NOTEWORTHY We report a profound upregulation of most egln paralog mRNA levels in anoxia and upon reoxygenation, with egln3ii 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.

低氧诱导因子(HIF)被认为是低氧转录反应的关键。然而,HIF 在缺氧(缺氧)和准备复氧时的作用仍不清楚。最近的研究表明,启动 HIF 响应可能会对缺氧生存产生反作用。我们在此研究了缺氧生存冠军鲫鱼(Carassius carassius),并假设脯氨酰羟化酶结构域 PHDs(HIF 的上游调节因子)的表达会上调,以规避缺氧状态下 HIF 高能耗的激活,并为复氧做好准备。我们使用 qPCR 和 Western 印迹技术测量了暴露于 5 天常氧或缺氧以及 5 天缺氧后 3 小时或 24 小时复氧的鲫鱼大脑中 PHD1、2 和 3 三种异构体(由 egln2、1 和 3 基因的多个旁系亲属编码)的 mRNA 和蛋白质水平。大多数egln旁系亲属的mRNA水平在缺氧和复氧时都有所增加,其中egln3的mRNA水平增幅最大(高达20倍),相对mRNA丰度也最高(高达所表达eglns的75%)。在缺氧状态下,所有 PHDs 的蛋白水平均保持不变,而在复氧后则有所提高。我们随后探究了PHDs在不同脑区的分布,发现PHDs免疫反应与轴突分支相关,并在缺氧-复氧过程中表现出区域特异性变化。我们的研究结果表明,在鲫鱼长期缺氧的情况下,eglns总体上调,而在复氧时,PHDs上调,其目的可能是抑制HIF反应,尽管在大脑这样一个复杂的器官中,区域差异是显而易见的。
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引用次数: 0
Input-size dependence of the baroreflex neural arc transfer characteristics during Gaussian white noise inputs. 高斯白噪声输入下压力反射神经弧传递特性的输入大小依赖性。
IF 2.8 3区 医学 Q3 PHYSIOLOGY Pub Date : 2024-02-01 Epub Date: 2023-12-04 DOI: 10.1152/ajpregu.00199.2023
Toru Kawada, Tadayoshi Miyamoto, Masafumi Fukumitsu, Keita Saku

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 (n = 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, P < 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 R2 values compared with the linear model and the previously suggested second-order Uryson model in the testing dataset.NEW & NOTEWORTHY 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 R2 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.

尽管高斯白噪声(GWN)输入为识别高阶非线性提供了理论框架,但对颈动脉窦压力反射神经弧数据的实际应用并不能成功地完全预测众所周知的s型非线性。在本研究中,我们假设神经弧可以用线性动态(LD)分量和非线性静态(NS)分量的级联来近似。我们分析了麻醉大鼠(n = 7)使用GWN输入(平均120 mmHg,标准差10、20和30 mmHg,各15分钟)获得的数据。我们首先估计了颈动脉窦压到交感神经活动(SNA)的线性传递函数,然后绘制了测量的SNA与线性预测的SNA的对比图。根据线性预测SNA的大小,将预测和测量的数据对分成10个箱时,呈现逆s型分布。通过LD-NS模型估计的s型非线性显示,SD为30 mmHg时,中点压力(104.1±4.4 mmHg)低于传统逐步输入估计的中点压力(135.8±3.9 mmHg, P < 0.001)。这表明,NS成分更有可能反映在脉动输入期间观察到的非线性,这对压力感受器来说是生理的。此外,在测试数据集中,LD-NS模型比线性模型和先前建议的二阶Uryson模型产生更高的R2值。
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引用次数: 0
Differences in the range of thermoneutral zone between mouse strains: potential effects on translational research. 小鼠品系间热中性区范围的差异-对转译研究的潜在影响。
IF 2.8 3区 医学 Q3 PHYSIOLOGY Pub Date : 2024-02-01 Epub Date: 2023-11-27 DOI: 10.1152/ajpregu.00154.2023
Andrzej K Gębczyński, Julita Sadowska, Marek Konarzewski

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.

实验室小鼠通常用于模拟人体代谢的研究。为了提供人体能量,他们的每日(DEE)与基础(BMR)能量消耗的比率应保持在1.7-1.8。然而,DEE/BMR比率在很大程度上取决于使用小鼠模型的给定研究是否高于或低于热中性区的较低临界温度(LCT),这在转化研究中很少考虑。在这里,我们使用人工选择的高或低BMR率的小鼠以及文献数据来分析环境温度对DEE/BMR可能的系统偏差的影响。我们证明,来自高BMR和低BMR系的小鼠的估计lct相差超过7°C。此外,用于转化研究的小鼠品系的LCTs变化范围为23至33°C。我们所选小鼠的LCT与其他小鼠品系的差异反映在它们的DEE/BMR比率的差异上,在低于LCT的温度下,其平均增加率为0.172°C-1。鉴于不同小鼠品系的lct范围广泛,我们得出结论,不同小鼠品系的体温调节的能量成本可能存在很大差异,这可能对翻译结果产生很大影响。因此,给定小鼠品系的LCT是设计转译研究时必须考虑的一个重要因素。
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引用次数: 0
Muscle metaboreflex stimulates the cardiac sympathetic afferent reflex causing positive feedback amplification of sympathetic activity: effect of heart failure. 肌肉代谢反射刺激心脏交感神经传入反射,引起交感神经活动的正反馈放大:心力衰竭效应。
IF 2.2 3区 医学 Q3 PHYSIOLOGY Pub Date : 2024-02-01 Epub Date: 2023-11-27 DOI: 10.1152/ajpregu.00235.2023
Joseph Mannozzi, Danielle Senador, Jasdeep Kaur, Matthew Gross, Megan McNitt, Alberto Alvarez, Beruk Lessanework, Donal S O'Leary

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.NEW & NOTEWORTHY 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.

运动不耐受是心力衰竭的一个标志性症状,在很大程度上源于心输出量的减少,这是由于固有的心室功能障碍加上肌肉代谢反射增强引起的功能性冠状动脉血管收缩,从而限制了冠状动脉血流的增加。这造成了氧气输送和氧气需求之间的进一步不匹配,这可能会激活心脏交感传入反射(CSAR),导致已经增加的交感神经活动以正反馈的方式放大。我们利用我们的长期有意识的犬模型来评估慢性消融负责CSAR的传入神经是否会减弱诱发心力衰竭前后肌肉代谢反射的增加。传入消融术后,肌肉代谢反射控制的平均动脉压增益在诱发心力衰竭前(-239.5±16 ~ -95.2±8 mmHg/l/min)和诱导心力衰竭后(-185.6±14 ~ -95.7±12 mmHg/l/min)显著降低。在心率、心输出量和心室收缩力的肌肉代谢反射控制的强度(增益)方面也观察到类似的结果。因此,我们得出结论,在正常和心力衰竭动物中,CSAR作为有效的正反馈放大器,对肌肉代谢反射的强度有显著贡献,从而进一步增加交感神经活动。
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American journal of physiology. Regulatory, integrative and comparative physiology
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