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Journal of applied physiology
The Americal Physiological Society
Journal of applied physiology

The Americal Physiological Society

8750-7587

Journal of applied physiology/Journal Journal of applied physiologySCIAHCIISTP
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    Xanthine oxidoreductase activity in marathon runners: potential implications for marathon-induced acute kidney injury.

    Keisei KosakiShota KumamotoKatsuyuki TokinoyaYasuko Yoshida...
    10页
    查看更多>>摘要：Excess activation of circulating xanthine oxidoreductase (XOR) may contribute to the pathogenesis of widespread remote organ injury, including kidney injury. The purpose of this study was to determine the acute impact of marathon running on plasma XOR activity and to examine whether plasma XOR activity is associated with marathon-induced elevations in biomarkers of acute kidney injury (AKI). Twenty-three young men (aged 20-25 yr) who participated in the 38th Tsukuba Marathon were included. Blood and urine samples were collected before, immediately, 2 h (only blood sample), and 24 h after a full marathon run. Plasma XOR activity was evaluated using a highly sensitive assay utilizing a combination of [~(13)C_(2),~(15)N_(2)] xanthine and liquid chromatography-triple quadrupole mass spectrometry. The levels of several AKI biomarkers, such as serum creatinine and urinary liver-type fatty acid-binding protein (L-FABP) were measured in each participant. Marathon running caused a transient elevation in plasma XOR activity and levels of purine degradation products (hypoxanthine, xanthine, and uric acid) as well as serum creatinine, urinary albumin, and urinary L-FABP levels. Immediately after the marathon, individual relative changes in plasma XOR activity were independently correlated with corresponding changes in serum creatinine and urinary L-FABP levels. In addition, the magnitude of marathon-induced elevation in plasma XOR activity and levels of purine degradation products were higher in individuals who developed AKI. These findings collectively suggest that marathon running substantially influences the purine metabolism pathway including XOR activity. Moreover, activated circulating XOR can be partly associated with elevated biomarkers of AKI after marathon running.<b>NEW & NOTEWORTHY This study is the first to show marathon running transiently increases plasma XOR activity and levels of purine degradation products (hypoxanthine, xanthine, and uric acid), and further to demonstrate that activated plasma XOR may contribute to marathon-induced elevations in biomarkers of AKI. These findings significantly extend our prior knowledge of the purine metabolic pathway and several AKI biomarkers under strenuous exercise conditions.
      原文链接:
    • NSTL
    • Amer Physiological Soc

    In vivo localized gastrocnemius subtendon representation within the healthy and ruptured human Achilles tendon.

    Ra'ad M KhairLauri StenrothNeil J CroninAleksi Reito...
    9页
    查看更多>>摘要：The Achilles tendon (AT) is composed of three distinct in-series elastic subtendons, arising from different muscles in the triceps surae. Independent activation of any of these muscles is thought to induce sliding between the adjacent AT subtendons. We aimed to investigate displacement patterns during voluntary contraction (VOL) and selective transcutaneous stimulation of medial (MG_(stim)) and lateral (LG_(stim)) gastrocnemius between ruptured and healthy tendons and to examine the representative areas of AT subtendons. Twenty-eight patients with unilateral AT rupture performed bilateral VOL at 30% of the maximal isometric uninjured plantarflexion torque. AT displacement was analyzed from sagittal B-mode ultrasonography images during VOL, MG_(stim), and LG_(stim). Three-way ANOVA revealed a significant two-way interaction of contraction type × location on the tendon displacement [<i>F (10-815) = 3.72,<i>P < 0.001]. The subsequent two-way analysis revealed a significant contraction type × location interaction for tendon displacement [<i>F (10-410)=3.79,<i>P < 0.001] in the uninjured limb only, where LG_(stim)displacement pattern was significantly different from MG_(stim)(<i>P = 0.008) and VOL (<i>P = 0.005). When comparing contraction types between limbs, there were no difference in the displacement patterns, but displacement amplitudes differed. There was no significant difference in the location of maximum or minimum displacement between limbs. The displacement pattern was not different in nonsurgically treated compared with uninjured tendons 1 yr after rupture. However, free tendon stiffness seems to be lower in the injured AT, leading to more displacement during electrically induced contractions compared with the uninjured. Our results suggest that near the calcaneus, LG subtendon is located in the most anterior region adjacent to medial gastrocnemius.<b>NEW & NOTEWORTHY Using selective electrical stimulation, we report the distributions of medial and lateral gastrocnemius subtendon representations within the healthy and ruptured Achilles tendon. In the majority of our sample, lateral gastrocnemius subtendon was found in the most anterior region adjacent to medial gastrocnemius both in the healthy and ruptured, nonsurgically treated tendon. The tendon internal displacement pattern does not seem to differ, but displacement amplitude and nonuniformity differed between healthy and ruptured tendons 1 yr after rupture.
      原文链接:
    • NSTL
    • Amer Physiological Soc

    Graded lower body negative pressure induces intraventricular negative pressures and incremental diastolic suction: a pressure-volume study in a porcine model.

    Leonhard BerbothBirgit ZirngastMartin ManningerPaul Steendijk...
    7页
    查看更多>>摘要：Lower body negative pressure (LBNP) is a tool to study compensatory mechanisms to central hypovolemia for decades. However, the underlying hemodynamic mechanisms were mostly assessed noninvasively and remain unclear. We hypothesized that incremental LBNP reduces diastolic filling and thereby affects left ventricular (LV) diastolic suction (DS). Here, we investigated the impact of graded LBNP at three different levels of seal as well as during β-adrenergic stimulation by invasive pressure-volume (PV) analysis. Eight Landrace pigs were instrumented closed-chest for PV assessment. LBNP was applied at three consecutive locations:<i>I ) cranial, 10 cm below xiphoid process;<i>II ) medial, half-way between cranial and caudal;<i>III ) caudal, at the iliac spine.<i>Level III was repeated under dobutamine infusion. At each level, baseline measurements were followed by application of incremental LBNP of -15, -30, and -45 mmHg. LBNP induced varying degrees of preload-dependent hemodynamic changes, with cranial LBNP inducing more pronounced effects than caudal. According to the Frank-Starling mechanism, graded LBNP progressively reduced LV stroke volume (LV SV) following a decrease in LV end-diastolic volume. Negative intraventricular minimal pressures were observed during dobutamine-infusion as well as higher levels of LBNP. Of note, incremental LV negative pressures were accompanied by increasing DS volumes, derived by extrapolating the volume at zero transmural pressure, the so-called equilibrium volume (<i>V _(0)), related to LV SV. In conclusion, graded preload reduction via LBNP shifts the PV loop to smaller volumes and end-systolic volume below<i>V _(0), which induces negative LV pressures and increases LV suction. Accordingly, LBNP-induced central hypovolemia is associated with increased DS.<b>NEW & NOTEWORTHY This study examined the effects of incremental lower body negative pressure (LBNP) from -15 to -45 mmHg on hemodynamic regulation using invasive pressure-volume assessment in closed-chest pigs. Graded preload reduction via LBNP induces negative left ventricular (LV) pressures while increasing LV suction and thus allowing the ventricle to eject below the equilibrium volume at the end of systole. Accordingly, LBNP-induced central hypovolemia is associated with increased diastolic suction.
      原文链接:
    • NSTL
    • Amer Physiological Soc

    Kidney injury risk during prolonged exposure to current and projected wet bulb temperatures occurring during extreme heat events in healthy young men.

    David HostlerZachary J SchladerHayden W HessJocelyn J Stooks...
    14页
    查看更多>>摘要：Wet bulb temperatures (T_(wet)) during extreme heat events are commonly 31°C. Recent predictions indicate that T_(wet)will approach or exceed 34°C. Epidemiological data indicate that exposure to extreme heat events increases kidney injury risk. We tested the hypothesis that kidney injury risk is elevated to a greater extent during prolonged exposure to T_(wet)= 34°C compared with T_(wet)= 31°C. Fifteen healthy men rested for 8 h in T_(wet)= 31 (0)°C and T_(wet)= 34 (0)°C. Insulin-like growth factor-binding protein 7 (IGFBP7), tissue inhibitor of metalloproteinase 2 (TIMP-2), and thioredoxin 1 (TRX-1) were measured from urine samples. The primary outcome was the product of IGFBP7 and TIMP-2 ([IGFBP7·TIMP-2]), which provided an index of kidney injury risk. Plasma interleukin-17a (IL-17a) was also measured. Data are presented at preexposure and after 8 h of exposure and as mean (SD) change from preexposure. The increase in [IGFBP7·TIMP-2] was markedly greater at 8 h in the 34°C [+26.9 (27.1) (ng/mL)~(2)/1,000) compared with the 31°C [+6.2 (6.5) (ng/mL)~(2)/1,000] trial (<i>P < 0.01). Urine TRX-1, a marker of renal oxidative stress, was higher at 8 h in the 34°C [+77.6 (47.5) ng/min] compared with the 31°C [+16.2 (25.1) ng/min] trial (<i>P < 0.01). Plasma IL-17a, an inflammatory marker, was elevated at 8 h in the 34°C [+199.3 (90.0) fg/dL;<i>P < 0.01] compared with the 31°C [+9.0 (95.7) fg/dL] trial. Kidney injury risk is exacerbated during prolonged resting exposures to T_(wet)experienced during future extreme heat events (34°C) compared with that experienced currently (31°C), likely because of oxidative stress and inflammatory processes.<b>NEW AND NOTEWORTHY We have demonstrated that kidney injury risk is increased when men are exposed over an 8-h period to a wet bulb temperature of 31°C and exacerbated at a wet bulb temperature of 34°C. Importantly, these heat stress conditions parallel those that are encountered during current (31°C) and future (34°C) extreme heat events. The kidney injury biomarker analyses indicate both the proximal and distal tubules as the locations of potential renal injury and that the injury is likely due to oxidative stress and inflammation.
      原文链接:
    • NSTL
    • Amer Physiological Soc

    CORP: Gene delivery into murine skeletal muscle using in vivo electroporation.

    David C HughesJustin P HardeeDavid S WaddellCraig A Goodman...
    19页
    查看更多>>摘要：The strategy of gene delivery into skeletal muscles has provided exciting avenues in identifying new potential therapeutics toward muscular disorders and addressing basic research questions in muscle physiology through overexpression and knockdown studies. In vivo electroporation methodology offers a simple, rapidly effective technique for the delivery of plasmid DNA into postmitotic skeletal muscle fibers and the ability to easily explore the molecular mechanisms of skeletal muscle plasticity. The purpose of this review is to describe how to robustly electroporate plasmid DNA into different hindlimb muscles of rodent models. Furthermore, key parameters (e.g., voltage, hyaluronidase, and plasmid concentration) that contribute to the successful introduction of plasmid DNA into skeletal muscle fibers will be discussed. In addition, details on processing tissue for immunohistochemistry and fiber cross-sectional area (CSA) analysis will be outlined. The overall goal of this review is to provide the basic and necessary information needed for successful implementation of in vivo electroporation of plasmid DNA and thus open new avenues of discovery research in skeletal muscle physiology.
      原文链接:
    • NSTL
    • Amer Physiological Soc

    Diaphragm muscle function in a mouse model of early-onset spasticity.

    Matthew J FogartyJoline E BrandenburgWen-Zhi ZhanGary C Sieck...
    9页
    查看更多>>摘要：Spasticity is a common symptom in many developmental motor disorders, including spastic cerebral palsy (sCP). In sCP, respiratory dysfunction is a major contributor to morbidity and mortality, yet it is unknown how spasticity influences respiratory physiology or diaphragm muscle (DIAm) function. To investigate the influence of spasticity on DIAm function, we assessed in vivo transdiaphragmatic pressure (Pdi - measured using intraesophageal and intragastric pressure catheters under conditions of eupnea, hypoxia/hypercapnia and occlusion) including maximum Pdi (Pdi_(max)via bilateral phrenic nerve stimulation), ex vivo DIAm-specific force and fatigue (using muscle strips stimulated with platinum plate electrodes), and type-specific characteristics of DIAm fiber cross sections (using immunoreactivity against myosin heavy chain slow and 2A) in<i>spa and wildtype mice.<i>Spa mice show reduced Pdi_(max), reduced DIAm specific force, and altered fatigability and atrophy of type IIx/IIb fibers. These findings suggest marked DIAm dysfunction may underlie the respiratory phenotype of sCP.<b>NEW & NOTEWORTHY Developmental motor control dysfunctions, including spastic cerebral palsy (sCP) often have respiratory components.<i>Spa mutant mice exhibit a spastic phenotype closely resembling sCP symptoms. Using the spa mouse model of spastic cerebral palsy (sCP), we quantified transdiaphragmatic pressure deficits, diaphragm muscle weakness, and fiber type-specific atrophy, improving our understanding of respiratory dysfunctions in sCP.
      原文链接:
    • NSTL
    • Amer Physiological Soc

    Prior beetroot juice ingestion offsets endothelial dysfunction following prolonged sitting.

    Takuma MorishimaMotoyuki IemitsuShumpei FujieEisuke Ochi...
    6页
    查看更多>>摘要：Nutritional strategies to prevent endothelial dysfunction following prolonged sitting remain largely unknown. Given that beetroot juice (BRJ) ingestion enhances nitric oxide (NO) bioavailability, we aimed to evaluate whether prior BRJ ingestion would prevent sitting-induced endothelial dysfunction in the leg. Eleven healthy young males (<i>n = 7) and females (<i>n = 4) underwent two experimental trials of prolonged sitting with prior:<i>1 ) placebo (PL) ingestion (PL trial) and<i>2 ) BRJ ingestion (BRJ trial). All subjects ingested 140 mL of PL or BRJ (～0.0055 or ～12.8 mmol of nitrate, respectively) immediately before 3 h of sitting. Pre- and post-sitting measurements of popliteal artery flow-mediated dilation (FMD) and blood pressure, and blood collection were undertaken. During the sitting period, an hourly assessment of popliteal artery diameter and blood velocity, blood pressure, and blood collection were performed. Popliteal artery blood flow and shear rate were significantly and similarly reduced during the sitting period in both trials (<i>P < 0.001). Plasma nitrate and NOx (total nitrite and nitrate) concentrations were significantly increased relative to baseline in the only BRJ trial, and the overall concentrations were significantly higher in the BRJ trial (<i>P < 0.001). Popliteal artery FMD was significantly reduced after the sitting period in the PL trial (<i>P < 0.05), whereas no reduction was observed in the BRJ trial. Therefore, prior BRJ ingestion would prevent sitting-induced leg endothelial dysfunction via enhancing NO bioavailability.<b>NEW & NOTEWORTHY The present study elucidates that beetroot juice ingestion before prolonged sitting offsets sitting-induced leg endothelial dysfunction. Data from the present study provides novel physiological information that enhancing NO bioavailability by dietary nitrate supplementation is an effective tool for prevention of the detrimental vascular effects of prolonged sitting.
      原文链接:
    • NSTL
    • Amer Physiological Soc

    Blood flow restriction and stimulated muscle contractions do not improve metabolic or vascular outcomes following glucose ingestion in young, active individuals.

    Jeremy N CohenMegan A KuikmanValerie Politis-BarberBrienne E Stairs...
    12页
    查看更多>>摘要：Glucose ingestion and absorption into the bloodstream can challenge glycemic regulation and vascular endothelial function. Muscular contractions in exercise promote a return to homeostasis by increasing glucose uptake and blood flow. Similarly, muscle hypoxia supports glycemic regulation by increasing glucose oxidation. Blood flow restriction (BFR) induces muscle hypoxia during occlusion and reactive hyperemia upon release. Thus, in the absence of exercise, electric muscle stimulation (EMS) and BFR may offer circulatory and glucoregulatory improvements. In 13 healthy, active participants (27?±?3 yr, 7 females), we tracked post-glucose (oral 100 g) glycemic, cardiometabolic, and vascular function measures over 120 min following four interventions:<i>1 ) BFR,<i>2 ) EMS,<i>3 ) BFR + EMS, or<i>4 ) control. BFR was applied at 2-min intervals for 30 min (70% occlusion), and EMS was continuous for 30 min (maximum-tolerable intensity). Glycemic and insulinemic responses did not differ between interventions (partial η~(2)= 0.11-0.15,<i>P = 0.2), however, only BFR + EMS demonstrated cyclic effects on oxygen consumption, carbohydrate oxidation, muscle oxygenation, heart rate, and blood pressure (all<i>P < 0.01). Endothelial function was reduced 60 min post-glucose ingestion across interventions and recovered by 120 min (5.9?±?2.6% vs 8.4?±?2.7%;<i>P < 0.001). Estimated microvascular function was not meaningfully different. Leg blood flow increased during EMS and BFR + EMS (+656?±?519 mL·min~(-1), +433?±?510 mL·min~(-1);<i>P < 0.001); however, only remained elevated following BFR intervention 90 min post-glucose (+94?±?94 mL·min~(-1);<i>P = 0.02). Superimposition of EMS onto cyclic BFR did not preferentially improve post-glucose metabolic or vascular function among young, active participants. Cyclic BFR increased blood flow delivery 60 min beyond intervention, and BFR + EMS selectively increased carbohydrate usage and reduced muscle oxygenation warranting future clinical assessments.<b>NEW & NOTEWORTHY Glucose ingestion challenges glycemic and vascular function. Exercise effectively counteracts these impairments, but is not always feasible. Blood flow restriction (BFR) and electric muscle stimulation (EMS) passively generate muscle hypoxia and contractions mimicking aspects of exercise. We tested BFR, EMS, and BFR + EMS in young, active participants post-glucose. No significant primary glycemic or vascular outcomes are observed. Cyclic BFR increased leg blood flow while BFR + EMS activated greater carbohydrate oxidation and lowered muscle oxygenation warranting future consideration.
      原文链接:
    • NSTL
    • Amer Physiological Soc

    The influence of longitudinal muscle fascicle growth on mechanical function.

    Avery HinksMartino V FranchiGeoffrey A Power
    17页
    查看更多>>摘要：Skeletal muscle has the remarkable ability to remodel and adapt, such as the increase in serial sarcomere number (SSN) or fascicle length (FL) observed after overstretching a muscle. This type of remodeling is termed longitudinal muscle fascicle growth, and its impact on biomechanical function has been of interest since the 1960s due to its clinical applications in muscle strain injury, muscle spasticity, and sarcopenia. Despite simplified hypotheses on how longitudinal muscle fascicle growth might influence mechanical function, existing literature presents conflicting results partly due to a breadth of methodologies. The purpose of this review is to outline what is currently known about the influence of longitudinal muscle fascicle growth on mechanical function and suggest future directions to address current knowledge gaps and methodological limitations. Various interventions indicate longitudinal muscle fascicle growth can increase the optimal muscle length for active force, but whether the whole force-length relationship widens has been less investigated. Future research should also explore the ability for longitudinal fascicle growth to broaden the torque-angle relationship's plateau region, and the relation to increased force during shortening. Without a concurrent increase in intramuscular collagen, longitudinal muscle fascicle growth also reduces passive tension at long muscle lengths; further research is required to understand whether this translates to increased joint range of motion. Finally, some evidence suggests longitudinal fascicle growth can increase maximum shortening velocity and peak isotonic power; however, there has yet to be direct assessment of these measures in a neurologically intact model of longitudinal muscle fascicle growth.
      原文链接:
    • NSTL
    • Amer Physiological Soc

    A leak-free head-out plethysmography system to accurately assess lung function in mice.

    Stephanie BrugginkKyle KentchJason KronenfeldBenjamin J Renquist...
    15页
    查看更多>>摘要：Mice are a valuable model for elegant studies of complex, system-dependent diseases, including pulmonary diseases. Current tools to assess lung function in mice are either terminal or lack accuracy. We set out to develop a low-cost, accurate, head-out variable-pressure plethysmography system to allow for repeated, nonterminal measurements of lung function in mice. Current head-out plethysmography systems are limited by air leaks that prevent accurate measures of volume and flow. We designed an inflatable cuff that encompasses the mouse's neck preventing air leak. We wrote corresponding software to collect and analyze the data, remove movement artifacts, and automatically calibrate each dataset. This software calculates volume, inspiratory/expiratory time, breaths per minute, mid-expiratory flow, and end-inspiratory pause. To validate the use, we established that our plethysmography system accurately measured tidal breathing, the bronchoconstrictive response to methacholine, sex- and age-associated changes in breathing, and breathing changes associated with house dust mite sensitization. Our estimates of volume, flow, and timing of breaths are in line with published estimates, we observed dose-dependent decreases in volume and flow in response to methacholine (<i>P < 0.05), increased lung volume, and decreased breathing rate with aging (<i>P < 0.05), and that house dust mite sensitization decreased volume and flow (<i>P < 0.05) while exacerbating the methacholine-induced increase in inspiratory time (<i>P < 0.05). We describe an accurate, sensitive, low-cost, head-out plethysmography system that allows for longitudinal studies of pulmonary disease in mice.<b>NEW & NOTEWORTHY We describe a low-cost, variable-pressure head-out plethysmography system that can be used to assess lung function in mice. A balloon cuff is inflated around the mouse's neck to prevent air leak, allowing for accurate measurements of lung volume and air flow. Custom software facilitates system calibration, removes movement artifacts, and eases data analysis. The system was validated by measuring tidal breathing, responses to methacholine, and changes associated with house dust mite sensitization, sex, and aging.
      原文链接:
    • NSTL
    • Amer Physiological Soc