bluuebunny/crossref_metadata_2025 huggingface dataset:
Different effects on human skeletal myosin heavy chain isoform expression: strength vs. combination training
Authors: Liu Y. , Schlumberger A. , Wirth K. , Schmidtbleicher D. , Steinacker J. M.
Published: March 2015

Myosin heavy chain (MHC) isoform expression changes with physical training. This may be one of the mechanisms for muscular adaptation to exercise. We aimed to investigate the effects of different strength-training protocols on MHC isoform expression, bearing in mind that α- MHCslow(newly identified MHC isoform) mRNA may be upregulated in response to training. Twelve volunteers performed a 6-wk strength training with maximum contractions (Max group), and another 12 of similar age performed combination training of maximum contractions and ballistic and stretch-shortening movements (Combi group). Muscle samples were taken from triceps brachii before and after training. MHC isoform composition was determined by SDS-PAGE silver staining, and mRNA levels of MHC isoforms were determined by RT-PCR. In Max group, there was an increase in MHC2A(49.4 to 66.7%, P< 0.01) and a decrease in MHC2X(33.4 to 19.5%, P < 0.01) after training, although there was no significant change in MHCslow. In Combi group, there was also an increase in MHC2A(47.7 to 62.7%, P < 0.05) and a decrease in MHCslow(18.2 to 9.2%, P < 0.05) but no significant change in MHC2X. An upregulation of α-MHCslowmRNA was, therefore, found in both groups as a result of training. The strength training with maximum contractions led to a shift in MHC isoform composition from 2X to 2A, whereas the combined strength training produced an MHC isoform composition shift from slow to 2A.
Invited Review: Genetic dissection of sleep
Authors: Tafti Mehdi , Franken Paul
Published: March 2015

Recent advances in genomics open up new avenues in the analysis of complex behaviors such as sleep. In this analysis, the mouse is the model species of choice because it is amenable to high throughput phenotype and genotype analysis. With the use of the mouse model, unprecedented progress in our understanding of sleep physiology and the treatment of sleep disorders is awaited. This review is intended to provide an overview of available methods and techniques for genetic dissection of sleep in mice. Limits and advantages of different approaches are discussed to highlight the necessity for combining methods to avoid erroneous interpretations. The gap between understanding mechanisms of sleep and its functions may be bridged by finding its molecular bases.
Invited Review: A neural clockwork for encoding circadian time
Authors: Herzog Erik D. , Schwartz William J.
Published: March 2015

10.1152/japplphysiol.00836.2001.—Many daily biological rhythms are governed by an innate timekeeping mechanism or clock. Endogenous, temperature-compensated circadian clocks have been localized to discrete sites within the nervous systems of a number of organisms. In mammals, the master circadian pacemaker is the bilaterally paired suprachiasmatic nucleus (SCN) in the anterior hypothalamus. The SCN is composed of multiple single cell oscillators that must synchronize to each other and the environmental light schedule. Other tissues, including those outside the nervous system, have also been shown to express autonomous circadian periodicities. This review examines 1) how intracellular regulatory molecules function in the oscillatory mechanism and in its entrainment to environmental cycles; 2) how individual SCN cells interact to create an integrated tissue pacemaker with coherent metabolic, electrical, and secretory rhythms; and 3) how such clock outputs are converted into temporal programs for the whole organism.
Paraventricular oxytocin neurons are involved in neural modulation of breathing
Authors: Mack S. O. , Kc P. , Wu M. , Coleman B. R. , Tolentino-Silva F. P. , Haxhiu M. A.
Published: March 2015

In this study, we determined the projections of oxytocin-containing neurons of the paraventricular nucleus (PVN) to phrenic nuclei and to the rostral ventrolateral medullary (RVLM) region, which is known to be involved in respiratory rhythm generation. Studies were also designed to determine oxytocin-receptor expression within the RVLM and the physiological effects of their activation on respiratory drive and arterial blood pressure. Oxytocin immunohistochemistry combined with cholera toxin B, a retrograde tracer, showed that a subpopulation of oxytocin-containing parvocellular neurons in the dorsal and medial ventral regions of the PVN projects to phrenic nuclei. Similarly, a subpopulation of pseudorabies virus-labeled neurons in the PVN coexpressed oxytocin after injection of pseudorabies virus, a transynaptic retrograde marker, into the costal region of the diaphragm. A subpopulation of oxytocin expressing neurons was also found to project to the RVLM. Activation of this site by microinjection of oxytocin into the RVLM (0.2 nmol/200 nl) significantly increased diaphragm electromyographic activity and frequency discharge ( P < 0.05). In addition, oxytocin increased blood pressure and heart rate ( P < 0.05). These data indicate that oxytocin participates in the regulation of respiratory and cardiovascular activity, partly via projections to the RVLM and phrenic nuclei.
Brain temperature measured by 1H-NMR in conjunction with a lanthanide complex
Authors: Trübel Hubert K. F. , Maciejewski Paul K. , Farber Jacqueline H. , Hyder Fahmeed
Published: March 2015

In vivo data on temperature distributions in the intact brain are scarce, partly due to lack of noninvasive methods for the region of interest. NMR has been exploited for probing a variety of brain activities in vivo noninvasively within the region of interest. Here we report the use of a thulium-based thermometric sensor, infused through the blood, for monitoring absolute temperature in rat brain in vivo by1H-NMR and validated by direct temperature measurements with thermocouple wires. Because the 1H chemical shifts also demonstrate pH sensitivity, detection of multiple resonances was used to measure both temperature and pH simultaneously with high sensitivity. Examination of blood plasma and cerebral spinal fluid samples removed from rats infused with the thermometric sensor suggests that the complex, despite its negative charge, crosses the blood-brain barrier to enter the extracellular milieu. In the future, the thulium-based thermometric sensor may be used for monitoring temperature (and pH) distributions throughout the entire brain, examining response to therapy and evaluating changes induced by alterations in neuronal activity.
Femoral artery inflow in relation to external and total work rate at different knee extensor contraction rates
Authors: Osada Takuya , Rådegran Göran
Published: March 2015

Whether limb blood flow is directly regulated to match the work rate, independent of the rate of contraction, remains elusive. This study therefore investigated the relationship between femoral arterial blood flow (FABF; Doppler ultrasound) and “external” (applied load) as well as “total” [external + “internal” (potential and kinetic energy changes of the moving lower leg)] work rate, during steady-state one-legged, dynamic, knee extensor exercise (1L-KEE) in the sitting position at different contraction rates. Ten subjects performed 1L-KEE at 30, 60, and 90 contractions/min (cpm) 1) at constant resistive loads of 0.2 and 0.5 kg inducing incremental external work rates ( study I) and 2) at different relative resistive loads inducing constant external work rates of 9 and 18 W ( study II). Moreover, 3) six subjects performed 1L-KEE at 60 and 100 cpm at incremental total work rates of 40, 50, 60, and 70 W ( study III). In study I, FABF increased ( P < 0.001) with increasing contraction frequency and external work rate, for each resistive load. In study II, FABF increased ( P < 0.001) with increasing contraction frequency for each constant external work rate. Of major importance in study III, however, was that FABF, although increasing linearly with the total work rate, was not different ( P= not significant) between contraction rates, at the total work rates of 40, 50, 60, and 70 W, respectively. Furthermore, FABF correlated linearly and positively with both the external and total work rate for each contraction frequency. In conclusion, the findings support the concept that leg blood flow during 1L-KEE in a normal knee extensor ergometer is matched directly in relation to the total work rate and metabolic activity, irrespective of the contraction frequency. The rate of contraction seems erroneously to influence the results only when it is related to the external work rate without taking into account the internal work component.
Role of kallikrein-kininogen system in insulin-stimulated glucose transport after muscle contractions
Authors: Dumke C. L. , Kim J. , Arias E. B. , Cartee G. D.
Published: March 2015

Serum proteins [molecular weight (MW) > 10,000] are essential for increased insulin-stimulated glucose transport after in vitro muscle contractions. We investigated the role of the kallikrein-kininogen system, including bradykinin, which is derived from kallikrein (MW > 10,000)-catalyzed degradation of serum protein kininogen (MW > 10,000), on this contraction effect. In vitro electrical stimulation of rat epitrochlearis muscles was performed in 1) rat serum ± kallikrein inhibitors; 2) human plasma (normal or kallikrein-deficient); 3) rat serum ± bradykinin receptor-2 inhibitors; or 4) serum-free buffer ± bradykinin. 3- O-methylglucose transport (3-MGT) was measured 3.5 h later. Serum ± kallikrein inhibitors tended ( P = 0.08) to diminish postcontraction insulin-stimulated 3-MGT. Contractions in normal plasma enhanced insulin-stimulated 3-MGT vs. controls, but contractions in kallikrein-deficient plasma did not. Supplementing rat serum with bradykinin receptor antagonist HOE-140 during contraction did not alter insulin-stimulated 3-MGT. Muscles stimulated to contract in serum-free buffer plus bradykinin did not have enhanced insulin-stimulated 3-MGT. Bradykinin was insufficient for postcontraction-enhanced insulin sensitivity. However, results with kallikrein inhibitors and kallikrein-deficient plasma suggest kallikrein plays a role in this improved insulin action.
Selected Contribution: Effects of sleep-wake state on the genioglossus vs. diaphragm muscle responses to CO2 in rats
Authors: Horner Richard L. , Liu Xia , Gill Harmeet , Nolan Philip , Liu Hattie , Sood Sandeep
Published: March 2015

The effects of sleep on the ventilatory responses to hypercapnia have been well described in animals and in humans. In contrast, there is little information for genioglossus (GG) responses to a range of CO2 stimuli across all sleep-wake states. Given the notion that sleep, especially rapid eye movement (REM) sleep, may cause greater suppression of muscles with both respiratory and nonrespiratory functions, this study tests the hypothesis that GG activity will be differentially affected by sleep-wake states with major suppression in REM sleep despite excitation by CO2. Seven rats were chronically implanted with electroencephalogram, neck, GG, and diaphragm electrodes, and responses to 0, 1, 3, 5, 7, and 9% CO2 were recorded. Diaphragm activity and respiratory rate increased with CO2 ( P < 0.001) across sleep-wake states with significant increases at 3–5% CO2 compared with 0% CO2 controls ( P < 0.05). Phasic GG activity also increased in hypercapnia but required higher CO2 (7–9%) for significant activation ( P < 0.05). Further studies in 15 urethane-anesthetized rats with the vagi intact ( n = 6) and cut ( n = 9) showed that intact vagi delayed GG recruitment with hypercapnia but did not affect diaphragm responses. In the naturally sleeping rats, we also showed that GG activity was significantly reduced in non-REM and REM sleep ( P < 0.04) and was almost abolished in REM even with stimulation by 9% CO2 (decrease = 80.4% vs. wakefulness). Such major suppression of GG activity in REM, even with significant respiratory stimulation, may explain why obstructive apneas are more common in REM sleep.
Critical developmental period for hyperoxia-induced blunting of hypoxic phrenic responses in rats
Authors: Bavis R. W. , Olson E. B. , Mitchell G. S.
Published: March 2015

Hypoxic ventilatory and phrenic responses are reduced in adult rats reared in hyperoxia (60% O2) for the first month of life but not after hyperoxia as adults. In this study, we identified the developmental window for susceptibility to hyperoxia. Phrenic nerve responses to hypoxia were recorded in anesthetized, vagotomized, paralyzed, and ventilated Sprague-Dawley rats (aged 3–4 mo) exposed to 60% O2for the first, second, third, or fourth postnatal week. Responses were compared with control rats and with rats exposed to 60% O2for the first month of life. Phrenic minute activity (burst amplitude × frequency) increased less during isocapnic hypoxia (arterial Po 2 = 60, 50, and 40 Torr) in rats exposed to hyperoxia for the first or second week, or the first month, of life ( P < 0.01 vs. control). Functional impairment caused by 1 wk of hyperoxia diminished with increasing age of exposure ( P = 0.005). Adult hypoxic phrenic responses are impaired by 1 wk of hyperoxia during the first and second postnatal weeks in rats, indicating a developmental window coincident with carotid chemoreceptor maturation.
Reduced exercise arteriovenous O2difference in Type 2 diabetes
Authors: Baldi James C. , Aoina James L. , Oxenham Helen C. , Bagg Warwick , Doughty Robert N.
Published: March 2015

Maximal O2consumption (V˙o2 max) is lower in individuals with Type 2 diabetes than in sedentary nondiabetic individuals. This study aimed to determine whether the lowerV˙o2 maxin diabetic patients was due to a reduction in maximal cardiac output (Q˙max) and/or peripheral O2extraction. After 11 Type 2 diabetic patients and 12 nondiabetic subjects, matched for age and body composition, who had not exercised for 2 yr, performed a bicycle ergometer exercise test to determine V˙o2 max, submaximal cardiac output, Q˙max, and arterial-mixed venous O2(a-v̄ O2) difference were assessed. Maximal workload, V˙o2 max, and maximal a-v̄ O2difference were lower in Type 2 diabetic patients ( P < 0.05). Q˙maxwas low in both groups but not significantly different: 11.2 and 10.0 l/min for controls and diabetic patients, respectively ( P > 0.05). Submaximal O2uptake and heart rate were lower at several workloads in diabetic patients; respiratory exchange ratio was similar between groups at all workloads.V˙o2 maxwas linearly correlated with a-v̄ O2difference, but not Q˙maxin diabetic patients. These data suggest that a reduction in maximal a-v̄ O2difference contributes to a decreasedV˙o2 maxin Type 2 diabetic patients.
Neuromuscular fatigue during a long-duration cycling exercise
Authors: Lepers Romuald , Maffiuletti Nicola A. , Rochette Ludovic , Brugniaux Julien , Millet Guillaume Y.
Published: March 2015

The effects of prolonged cycling on neuromuscular parameters were studied in nine endurance-trained subjects during a 5-h exercise sustained at 55% of the maximal aerobic power. Torque during maximal voluntary contraction (MVC) of the quadriceps muscle decreased progressively throughout the exercise ( P < 0.01) and was 18% less at the end of exercise compared with the preexercise value. Peak twitch torque, contraction time, and total area of mechanical response decreased significantly ( P < 0.05) after the first hour of exercise. In contrast, changes in M-wave characteristics were significant only after the fourth hour of the exercise. Significant reductions ( P < 0.05) in electromyographic activity normalized to the M wave occurred after the first hour for the vastus lateralis muscle but only at the end of the exercise for the vastus medialis muscle. Muscle activation level, assessed by the twitch interpolation technique, decreased by 8% ( P < 0.05) at the end of the exercise. The results suggest that the time course is such that the contractile properties are significantly altered after the first hour, whereas excitability and central drive are more impaired toward the latter stages of the 5-h cycling exercise.
fMRI responses to cold pressor challenges in control and obstructive sleep apnea subjects
Authors: Harper Ronald M. , Macey Paul M. , Henderson Luke A. , Woo Mary A. , Macey Katherine E. , Frysinger Robert C. , Alger Jeffry R. , Nguyen Khanh P. , Yan-Go Frisca L.
Published: March 2015

Obstructive sleep apnea (OSA) patients exhibit altered sympathetic outflow, which may reveal mechanisms underlying the syndrome. We used functional MRI (fMRI) in 16 control and 10 OSA subjects who were free of cardiovascular or mood-altering drugs to examine neural responses to a forehead cold pressor challenge, which elicits respiratory slowing, bradycardia, and enhanced sympathetic outflow. The magnitude of cold-induced bradycardia was smaller, and respiratory slowing showed greater intersubject variability and reached a nadir later in OSA patients. Both groups showed similar signal changes to cold stimulation in multiple brain sites. However, signal increases emerged in OSA over controls in anterior and posterior cingulate and cerebellar and frontal cortex, whereas signals markedly declined in the ventral thalamus, hippocampus, and insula rather than rising as in controls. Anomalous responses often paralleled changes in breathing and heart rate. Medullary, midbrain areas and lentiform and cerebellar dentate nuclei also showed lower signals in OSA cases. Cold pressor physiological responses are modified in OSA and may result from both diminished and exaggerated responses in multiple brain structures.
Effects of creatine supplementation and exercise training on fitness in men 55–75 yr old
Authors: Eijnde Bert O. , Van Leemputte Marc , Goris Marina , Labarque Valery , Taes Youri , Verbessem Patricia , Vanhees Luc , Ramaekers Monique , Vanden Eynde Bart , Van Schuylenbergh Reinout , Dom René , Richter Erik A. , Hespel Peter
Published: March 2015

effect of oral creatine supplementation (CR; 5 g/day) in conjunction with exercise training on physical fitness was investigated in men between 55 and 75 yr of age ( n = 46). A double-blind randomized placebo-controlled (PL) trial was performed over a 6-mo period. Furthermore, a subgroup ( n = 20) completed a 1-yr follow-up. The training program consisted of cardiorespiratory endurance training as well as moderate resistance training (2–3 sessions/wk). Endurance capacity was evaluated during a maximal incremental bicycle ergometer test, maximal isometric strength of the knee-extensor muscles was assessed by an isokinetic dynamometer, and body composition was assessed by hydrostatic weighing. Furthermore, in a subgroup (PL: n = 13; CR: n = 12) biopsies were taken from m. vastus lateralis to determine total creatine (TCr) content. In PL, 6 mo of training increased peak oxygen uptake rate (+16%; P < 0.05). Fat-free mass slightly increased (+0.3 kg; P < 0.05), whereas percent body fat slightly decreased (-1.2%; P < 0.05). The training intervention did not significantly change either maximal isometric strength or body weight. The responses were independent of CR. Still, compared with PL, TCr was increased by ∼5% in CR, and this increase was closely correlated with initial muscle creatine content ( r = -0.78; P < 0.05). After a 1-yr follow-up, muscle TCr was not higher in CR than in PL. Furthermore, the other measurements were not affected by CR. It is concluded that long-term creatine intake (5 g/day) in conjunction with exercise training does not beneficially impact physical fitness in men between 55 and 75 yr of age.
Lung perfusion impairments in pulmonary embolic and airway obstruction with noncontrast MR imaging
Authors: Suga Kazuyoshi , Ogasawara Nobuhiko , Okada Munemasa , Tsukuda Toshinobu , Matsunaga Naofumi , Miyazaki Mitsue
Published: March 2015

A noncontrast electrocardiography (ECG)-gated, fast-spin-echo magnetic resonance imaging was applied to noninvasively define perfusion impairments in pulmonary embolic and airway obstruction dog models. Two-phase ECG-gated lung images of the minimal lung signal intensity during systole and maximal signal intensity during diastole were acquired by using optimized R-wave triggering delay times in seven dogs anesthetized with pentobarbital sodium before, soon after, and 2 mo after embolization with enbucrilate and in another eight dogs before and after bronchial occlusion with balloon catheters, in combination with a gadolinium diethylenetriaminepentaacetic acid-enhanced dynamic study. An ECG-gated subtraction image between the two-phase lung images provided a uniform but gravity-dependent perfusion map in normal lungs. Furthermore, it defined all 13 variable-size perfusion deficits associated with pulmonary embolism and the dynamically decreased perfusion with time after bronchial occlusion in all the airway obstruction models. These results were consistent with contrast-enhanced pulmonary arterial perfusion phase images. This noncontrast imaging could be equivalent to a contrast-enhanced dynamic study in the definition of regionally impaired pulmonary arterial perfusion in pulmonary embolism and airway obstruction.
Endothelium-dependent vasodilation in different rat hindlimb skeletal muscles
Authors: McAllister Richard M.
Published: March 2015

Few studies have examined potential for endothelium-dependent vasodilation in skeletal muscles of different fiber-type composition. We hypothesized that muscles composed of slow oxidative (SO)- and/or fast oxidative glycolytic (FOG)-type fibers have greater potential for endothelium-dependent vasodilation than muscles composed of fast glycolytic (FG)-type fibers. To test this hypothesis, the isolated perfused rat hindlimb preparation was used with a constant-flow, variable-pressure approach. Perfusion pressure was monitored continuously, and muscle-specific flows were determined by using radiolabeled microspheres at four time points: control, at peak effect of acetylcholine (ACh I; 1–2 × 10−4 M), at peak effect of ACh after infusion of an endothelial inhibitor (ACh II), and at peak effect of sodium nitroprusside (SNP; 4–5 × 10−4 M). Conductance was calculated by using pressure and flow data. In the SO-type soleus muscle, conductance increased with ACh and SNP, but the increase in conductance with ACh was partially abolished by the endothelial inhibitor N G-nitro-l-arginine methyl ester (control, 0.87 ± 0.19; ACh I, 2.07 ± 0.29; ACh II, 1.32 ± 0.15; SNP, 1.76 ± 0.19 ml · min−1 · 100 g−1 · mmHg−1; P < 0.05, ACh I and SNP vs. control). In the FOG-type red gastrocnemius muscle, similar findings were obtained (control, 0.64 ± 0.11; ACh I, 1.36 ± 0.21; ACh II, 0.73 ± 0.16; SNP, 1.30 ± 0.21 ml · min−1 · 100 g−1 · mmHg; P < 0.05, ACh I and SNP vs. control). In the FG-type white gastrocnemius muscle, neither ACh nor SNP increased conductance. Similar findings were obtained when muscles were combined into high- and low-oxidative muscle groups. Indomethacin had no effect on responses to ACh. These data indicate that endothelium-dependent vasodilation is exhibited by high-oxidative, but not low-oxidative, rat skeletal muscle. Furthermore, endothelium-dependent vasodilation in high-oxidative muscle appears to be primarily mediated by nitric oxide.
Efficacy of intermittent, regional microclimate cooling
Authors: Cheuvront Samuel N. , Kolka Margaret A. , Cadarette Bruce S. , Montain Scott J. , Sawka Michael N.
Published: March 2015

The vasomotor response to cold may compromise the capacity for microclimate cooling (MCC) to reduce thermoregulatory strain. This study examined the hypothesis that intermittent, regional MCC (IRC) would abate this response and improve heat loss when compared with constant MCC (CC) during exercise heat stress. In addition, the relative effectiveness of four different IRC regimens was compared. Five heat-acclimated men attempted six experimental trials of treadmill walking (∼225 W/m2) in a warm climate (dry bulb temperature = 30°C, dewpoint temperature = 11°C) while wearing chemical protective clothing (insulation = 2.1; moisture permeability = 0.32) with a water-perfused (21°C) cooling undergarment. The six trials conducted were CC (continuous perfusion) of 72% body surface area (BSA), two IRC regimens cooling 36% BSA by using 2:2 (IRC1) or 4:4 (IRC2) min on-off perfusion ratios, two IRC regimens cooling 18% BSA by using 1:3 (IRC3) or 2:6 (IRC4) min on-off perfusion ratios, and a no cooling (NC) control. Compared with NC, CC significantly reduced changes in rectal temperature (∼1.2°C) and heart rate (∼60 beats/min) ( P < 0.05). The four IRC regimens all provided a similar reduction in exercise heat strain and were 164–215% more efficient than CC because of greater heat flux over a smaller BSA. These findings indicate that the IRC approach to MCC is a more efficient means of cooling when compared with CC paradigms and can improve MCC capacity by reducing power requirements.
Diffusional screening in the human pulmonary acinus
Authors: Felici M. , Filoche M. , Sapoval B.
Published: March 2015

In the mammalian lung acini, O2 diffuses into quasi-static air toward the alveolar membrane, where the gas exchange with blood takes place. The O2 flux is then influenced by the O2diffusivity, the membrane permeability, and the acinus geometric complexity. This phenomenon has been recently studied in an abstract geometric model of the acinus, the Hilbert acinus (Sapoval B, Filoche M, and Weibel ER, Proc Natl Acad Sci USA 99: 10411, 2002). This is extended here to a more realistic geometry originated from the morphological model of Kitaoka et al. (Kitaoka K, Tamura S, and Takaki R, J Appl Physiol 88: 2260–2268, 2000). Two-dimensional numerical simulations of the steady-state diffusion equation with mixed boundary conditions are used to quantify the process. The alveolar O2 concentration, or partial pressure, and the O2 flux are computed and show that diffusional screening exists at rest. These results confirm that smaller acini are more efficient, as suggested for the Hilbert acini.
Antifibrotic effects of suramin in injured skeletal muscle after laceration
Authors: Chan Yi-Sheng , Li Yong , Foster William , Horaguchi Takashi , Somogyi George , Fu Freddie H. , Huard Johnny
Published: March 2015

Muscle injuries are very common in traumatology and sports medicine. Although muscle tissue can regenerate postinjury, the healing process is slow and often incomplete; complete recovery after skeletal muscle injury is hindered by fibrosis. Our studies have shown that decreased fibrosis could improve muscle healing. Suramin has been found to inhibit transforming growth factor (TGF)-β1 expression by competitively binding to the growth factor receptor. We conducted a series of tests to determine the antifibrotic effects of suramin on muscle laceration injuries. Our results demonstrate that suramin (50 μg/ml) can effectively decrease fibroblast proliferation and fibrotic-protein expression (α-smooth muscle actin) in vitro. In vivo, direct injection of suramin (2.5 mg) into injured murine muscle resulted in effective inhibition of muscle fibrosis and enhanced muscle regeneration, which led to efficient functional muscle recovery. These results support our hypothesis that prevention of fibrosis could enhance muscle regeneration, thereby facilitating more efficient muscle healing. This study could significantly contribute to the development of strategies to promote efficient muscle healing and functional recovery.
Regulation of brain water during acute hyperosmolality in ovine fetuses, lambs, and adults
Authors: Stonestreet Barbara S. , Oen-Hsiao Joyce M. , Petersson Katherine H. , Sadowska Grazyna B. , Patlak Clifford S.
Published: March 2015

In adult rats, when plasma osmolality increases, water flows across the blood-brain barrier down its concentration gradient from brain to plasma, and brain volume deceases. The brain responds to this stress by gaining osmotically active solutes, which limit water loss. This phenomenon is termed brain volume (water) regulation. We tested the hypothesis that brain volume regulation is more effective in young lambs and adult sheep than in fetuses, premature lambs, and newborn lambs. Brain water responses to acute hyperosmolality were measured in the cerebral cortex, cerebellum, and medulla of fetuses at 60 and 90% of gestation, premature ventilated lambs at 90% of gestation, newborn lambs, young lambs at 20–30 days of age, and adult sheep. After exposure of the sheep to increases in systemic osmolality with mannitol plus NaCl, brain water content and electrolytes were quantified. The ideal osmometer is a system in which impermeable solutes do not enter or leave in response to an osmotic stress. There were significant differences from an ideal osmometer in the cerebral cortex of fetuses at 90% of gestation, cerebral cortex, and cerebellum of newborn lambs, and cerebral cortex, cerebellum, and medulla of young lambs and adult sheep; however, there were no differences in the brain regions of fetuses at 60% of gestation and premature lambs, cerebellum and medulla of fetuses at 90% of gestation, and medulla of newborn lambs. We conclude that 1) brain water loss is maximal and brain volume regulation impaired in most brain regions of fetuses at 60 and 90% of gestation and premature lambs; 2) brain volume regulation develops first in the cerebral cortex of the fetuses at 90% of gestation and in the cerebral cortex and cerebellum of newborn lambs, and then it develops in the medulla of the lambs at 20–30 days of age; 3) brain water loss is limited and volume regulation present in the brain regions of young lambs and adult sheep; and 4) the ability of the brain to exhibit volume regulation develops in a region- and age-related fashion.
A biphasic model of limb venous compliance: a comparison with linear and exponential models
Authors: Risk Marcelo R. , Lirofonis Vasilios , Armentano Ricardo L. , Freeman Roy
Published: March 2015

Compliance is not linear within the physiological range of pressures, and linear modeling may not describe venous physiology adequately. Forearm and calf venous compliance were assessed in nine subjects. Venous compliance was modeled by using a biphasic model with high- and low-pressure linear phases separated by a breakpoint. This model was compared with a linear model and several exponential models. The biphasic, linear, and two-parameter exponential models best represented the data. The mean coefficient of determination for the biphasic model was greater than for the linear and exponential models in the calf (biphasic 0.94 ± 0.04, exponential 0.81 ± 0.16, P = not significant; and linear 0.54 ± 0.05, P < 0.05) and forearm (biphasic 0.83 ± 0.17, exponential 0.79 ± 0.15, P = not significant; and linear 0.51 ± 0.06, P < 0.05). The breakpoint pressure in the biphasic model was higher in the calf than the forearm, 34.4 ± 3.9 vs. 29.1 ± 4.5 mmHg, P < 0.05. A biphasic model can describe limb venous compliance and delineate differences in venous physiology at high and low pressures. The steep low-pressure phase of the compliance curve extends to higher pressures in the calf than in the forearm, thereby enlarging the range of pressures over which hemodynamic regulation by the calf venous circulation occurs.
Prolonged hypobaric hypoxemia attenuates vasopressin secretion and renal response to osmostimulation in men
Authors: Bestle Morten H. , Olsen Niels V. , Poulsen Troels D. , Roach Robert , Fogh-Andersen Niels , Bie Peter
Published: March 2015

Effects of hypobaric hypoxemia on endocrine and renal parameters of body fluid homeostasis were investigated in eight normal men during a sojourn of 8 days at an altitude of 4,559 m. Endocrine and renal responses to an osmotic stimulus (5% hypertonic saline, 3.6 ml/kg over 1 h) were investigated at sea level and on day 6 at altitude. Several days of hypobaric hypoxemia reduced body weight (−2.1 ± 0.4 kg), increased plasma osmolality (+5.3 ± 1.4 mosmol/kgH2O), elevated blood pressure (+12 ± 1 mmHg), reduced creatinine clearance (122 ± 6 to 96 ± 10 ml/min), inhibited the renin system (19.5 ± 2.0 to 10.9 ± 0.9 mU/l) and plasma vasopressin (1.14 ± 0.16 to 0.38 ± 0.06 pg/ml), and doubled circulating levels of norepinephrine (103 ± 16 to 191 ± 35 pg/ml) and endothelin-1 (3.0 ± 0.2 to 6.3 ± 0.6 pg/ml), whereas urodilatin excretion rate decreased from day 2 (all changes P < 0.05 compared with sea level). Plasma arginine vasopressin response and the antidiuretic response to hypertonic saline loading were unchanged, but the natriuretic response was attenuated. In conclusion, chronic hypobaric hypoxemia 1) elevates the set point of plasma osmolality-to-plasma vasopressin relationship, possibly because of concurrent hypertension, thereby causing hypovolemia and hyperosmolality, and 2) blunts the natriuretic response to hypertonic volume expansion, possibly because of elevated circulating levels of norepinephrine and endothelin, reduced urodilatin synthesis, or attenuated inhibition of the renin system.
Involvement of nitric oxide synthase in skeletal muscle adaptation to chronic overload
Authors: Smith Lori W. , Smith John D. , Criswell David S.
Published: March 2015

The purpose of this study was to determine the necessity of nitric oxide (NO) for hypertrophy and fiber-type transition in overloaded (OL) skeletal muscle. Endogenous NO production was blocked by administering N G-nitro-l-arginine methyl ester (l-NAME; 0.75 mg/ml; ∼100 mg · kg−1 · day−1) in drinking water. Thirty-eight female Sprague-Dawley rats (∼250 g) were randomly divided into four groups: control-nonoverloaded (Non-OL), control-OL, l-NAME-Non-OL, andl-NAME-OL. Chronic overload of the plantaris was induced bilaterally by surgical removal of the gastrocnemius and soleus. Rats in the Non-OL groups received sham surgeries. l-NAME treatment began 24 h before surgery and continued until the rats were killed 14 days postsurgery. Although OL induced hypertrophy in both control (+76%) and l-NAME (+39%) conditions ( P < 0.05), mean plantaris-to-body mass ratio in thel-NAME-OL group was significantly lower ( P< 0.05) than that in the control-OL group. Microphotometric analysis of histochemically determined fiber types revealed increases in cross-sectional area ( P < 0.05) for all fiber types (types I, IIA, and IIB/X) in the OL plantaris from control rats, whereas l-NAME-OL rats exhibited increases only in type I and IIB/X fibers. SDS-PAGE analysis of myosin heavy chain (MHC) composition in the plantaris indicated a significant ( P< 0.05) OL effect in the control rats. Specifically, the mean proportion of type I MHC increased 6% ( P < 0.05), whereas the proportion of type IIb MHC decreased ∼9% ( P < 0.05). No significant OL effects on MHC profile were observed in the l-NAME rats. These data support a role of NO in overload-induced skeletal muscle hypertrophy and fiber-type transition.
Measurement of meal-stimulated gastric acid secretion by in vivo gastric autotitration
Authors: Gardner Jerry D. , Ciociola Arthur A. , Robinson Malcolm
Published: March 2015

Measurement of meal- stimulated gastric acid secretion using manual intragastric titration is demanding in terms of personnel and specialized equipment. In the present study, we used a new method, in vivo gastric autotitration, to determine meal-stimulated gastric acid secretion. Gastric pH was measured every 4 s before, during, and after ingestion of a standard meal in 24 healthy subjects. Placebo, ranitidine (150 mg), ranitidine (75 mg), or famotidine (10 mg) was given 1 h after the beginning of the meal. Meal-stimulated gastric acid secretion was calculated from the amount of HCl required to titrate the homogenized standard meal to pH 2 in vitro (119 mmol) and the time required for the pH of the ingested meal to decrease to pH 2 in vivo. Values for pH were also converted to acid concentration (mM), and integrated acidity was calculated from the cumulative, time-weighted means of the acid concentrations for every fourth second of the postprandial recording period. Control meal-stimulated gastric acid secretion was 60 (40–71) mmol/h (median; interquartile range), and each histamine H2-receptor antagonist significantly decreased secretion by ∼50%. Meal-stimulated acid secretion correlated directly with postprandial integrated gastric acidity ( r = 0.72; P = 0.0001). Thus intragastric autotitration is a convenient, reproducible method for measuring gastric acid secretion after ingestion of a solid meal and offers several advantages over manual intragastric titration.
Maximizing quantitative accuracy of lung airway lumen and wall measures obtained from X-ray CT imaging
Authors: Saba Osama I. , Hoffman Eric A. , Reinhardt Joseph M.
Published: March 2015

To objectively quantify airway geometry from three-dimensional computed tomographic (CT) images, an idealized (circular cross section) airway model is parameterized by airway luminal caliber, wall thickness, and tilt angle. Using a two-dimensional CT slice, an initial guess for the airway center, and the full-width-half-maximum principle, we form an estimate of inner and outer airway wall locations. We then fit ellipses to the inner and outer airway walls via a direct least squares fit and use the major and minor axes of the ellipses to estimate the tilt and in-plane rotation angles. Convolving the airway model, initialized with these estimates, with the three-dimensional scanner point-spread function forms the predicted image. The difference between predicted and actual images is minimized by refining the model parameter estimates via a multidimensional, unconstrained, nonlinear minimization routine. When optimization converges, airway model parameters estimate the airway inner and outer radii and tilt angle. Results using a Plexiglas phantom show that tilt angle is estimated to within ±4° and both inner and outer radii to within one-half pixel when a “standard” CT reconstruction kernel is used. By opening up the ability to measure airways that are not oriented perpendicular to the scanning plane, this method allows evaluation of a greater sampling of airways in a two-dimensional CT slice than previously possible. In addition, by combining the tilt-angle compensation with the deconvolution method, we provide significant improvement over the previous full-width-half-maximum method for assessing location of the luminal edge but not the outer edge of the airway wall.
Altered functional coupling of coronary K+channels in diabetic dyslipidemic pigs is prevented by exercise
Authors: Mokelke E. A. , Hu Q. , Song M. , Toro L. , Reddy H. K. , Sturek M.
Published: March 2015

Chronic hyperglycemia and hypercholesterolemia have been shown to alter ionic currents in vascular smooth muscle. We tested the hypothesis that the combined effect of hyperglycemia and hyperlipidemia (diabetic dyslipidemia) would increase the Ca2+-sensitive K+(KCa) current as a compensatory response to an increase in intracellular Ca2+concentration. We also hypothesized that exercise training would prevent this elevation in KCacurrent. Miniature Yucatan swine were randomly assigned to five groups: control, standard pig chow (C, n = 6); hyperlipidemic, high-fat pig chow (H, n = 5); diabetic, standard pig chow (D, n = 7); diabetic, high-fat pig chow (“diabetic dyslipidemic,” DD, n = 12); and exercise-trained DD (DDX, n = 9). High-fat chow consisted of standard minipig chow supplemented with cholesterol (2%) and coconut oil. Increased coronary vasoconstriction assessed in vivo and in vitro in DD was prevented by exercise. Patch-clamp experiments performed on right coronary artery smooth muscle cells resulted in greater K+current densities in the H, D, and DD groups vs. the DDX group between -10 and 40 mV. In fura 2-loaded cells, current activated by caffeine-induced Ca2+release was greater in H, D, and DD compared with C and DDX ( P < 0.05), whereas intracellular Ca2+concentration was not different across groups. Finally, there were no differences in the KCaor Kvchannel protein content between groups. These data indicate that hyperglycemia, hyperlipidemia, and diabetic dyslipidemia lead to elevated whole cell K+current and increased functional coupling of KCaand Ca2+release. Endurance exercise prevented increased coupling of Ca2+release to KCachannel activation in diabetic dyslipidemia.
Mild renal hypertension alters run training effects on the frequency response of rat cardiomyocyte mechanics
Authors: Palmer Bradley M. , Mokelke Eric A. , Thayer Anne M. , Moore Russell L.
Published: March 2015

We examined the effects of run training on the frequency dependence of cardiomyocyte mechanics and intracellular calcium concentration ([Ca2+]i) dynamics in rats with mild renal hypertension. Male Fischer 344 rats aged 2–3 mo underwent a sham operation or stenosis of the left renal artery, which increased systolic blood pressure 20–30 mmHg. Half of the rats in each group underwent treadmill run training for >16 wk. Isolated cardiomyocytes were paced at 1.0 and 0.2 Hz in 2 mM external Ca2+ concentration at 29°C. Under these conditions, negative frequency responses, i.e., decreased value with increased frequency, were recorded for peak shortening, shortening velocity, and the integral of the [Ca2+]i transient in both groups. Run training amplified the negative frequency response for the integral of the [Ca2+]i transient in both groups, but it amplified the negative frequency response for the shortening dynamics only in the normotensive sham-operated and not in the hypertensive rats. These results, as well as others for relaxation parameters, suggest that renal hypertension altered the effects of run training on the frequency response for cardiomyocyte contractile apparatus and/or passive mechanical properties, which respond to [Ca2+]i.
Heterogeneous responses of human limbs to infused adrenergic agonists: a gravitational effect?
Authors: Pawelczyk James A. , Levine Benjamin D.
Published: March 2015

Unlike quadrupeds, the legs of humans are regularly exposed to elevated pressures relative to the arms. We hypothesized that this “dependent hypertension” would be associated with altered adrenergic responsiveness. Isoproterenol (0.75–24 ng · 100 ml limb volume−1 · min−1) and phenylephrine (0.025–0.8 μg · 100 ml limb volume−1 · min−1) were infused incrementally in the brachial and femoral arteries of 12 normal volunteers; changes in limb blood flow were quantified by using strain-gauge plethysmography. Compared with the forearm, baseline calf vascular resistance was greater (38.8 ± 2.5 vs. 26.9 ± 2.0 mmHg · 100 ml · min · ml−1; P < 0.001) and maximal conductance was lower (46.1 ± 11.9 vs. 59.4 ± 13.4 ml · ml−1 · min−1 · mmHg−1; P < 0.03). Vascular conductance did not differ between the two limbs during isoproterenol infusions, whereas decreases in vascular conductance were greater in the calf than the forearm during phenylephrine infusions ( P < 0.001). With responses normalized to maximal conductance, the half-maximal response for phenylephrine was significantly less for the calf than the forearm ( P < 0.001), whereas the half-maximal response for isoproterenol did not differ between limbs. We conclude that α1- but not β-adrenergic-receptor responsiveness in human limbs is nonuniform. The relatively greater response to α1-adrenergic-receptor stimulation in the calf may represent an adaptive mechanism that limits blood pooling and capillary filtration in the legs during standing.
Severe muscle dysfunction precedes collagen tissue proliferation inmdxmouse diaphragm
Authors: Coirault Catherine , Pignol Bernadette , Cooper Racquel N. , Butler-Browne Gillian , Chabrier Pierre-Etienne , Lecarpentier Yves
Published: March 2015

After extensive necrosis, progressive diaphragm muscle weakness in the mdx mouse is thought to reflect progressive replacement of contractile tissue by fibrosis. However, little has been documented on diaphragm muscle performance at the stage at which necrosis and fibrosis are limited. Diaphragm morphometric characteristics, muscle performance, and cross-bridge (CB) properties were investigated in 6-wk-old control (C) and mdx mice. Compared with C, maximum tetanic tension and shortening velocity were 37 and 32% lower, respectively, in mdx mice (each P < 0.05). The total number of active CB per millimeter squared (13.0 ± 1.2 vs. 18.4 ± 1.7 × 109/mm2, P < 0.05) and the CB elementary force (8.0 ± 0.2 vs. 9.0 ± 0.1 pN, P < 0.01) were lower in mdx than in C. The time cycle duration was lower in mdx than in C (127 ± 18 vs. 267 ± 61 ms, P < 0.05). Percentages of fiber necrosis represented 2.8 ± 0.6% of the total muscle fibers, and collagen surface area occupied 3.6 ± 0.7% in mdx diaphragm. Our results pointed to severe muscular dysfunction in mdx mouse diaphragm, despite limited necrotic and fibrotic lesions.
Resting tension characteristics in differentiating intact rat fast- and slow-twitch muscle fibers
Authors: Mutungi Gabriel , Trinick John , Ranatunga K. W.
Published: March 2015

The postnatal changes in resting muscle tension were investigated at 20°C by using small muscle fiber bundles isolated from either the extensor digitorum longus or the soleus of both neonatal (7–21 days old) and adult rats. The results show that the tension-extension characteristics of the bundles depended on the age of the rats. For example, both the extensor digitorum longus and soleus bundles of rats older than 14 days showed characteristic differences that were absent in bundles from younger rats. Furthermore, the tension-extension relation of the adult slow muscle fiber bundles were similar to those of the two neonatal muscles and were shifted to longer sarcomere lengths relative to those of the adult fast-fiber bundles. Thus, at the extended sarcomere length of 2.9 μm, the adult fast muscle fiber bundles developed higher resting tensions (5.6 ± 0.5 kN/m2) than either the two neonatal (∼3 kN/m2) or the adult slow (3.1 ± 0.4 kN/m2) muscle fiber bundles. At all ages examined, the resting tension responses to a ramp stretch were qualitatively similar and consisted of three components: a viscous, a viscoelastic, and an elastic tension. However, in rats older than 14 days, all three tension components showed clear fast- and slow-fiber type differences that were absent in younger rats. Bundles from 7-day-old rats also developed significantly lower resting tensions than the corresponding adult ones. Additionally, the resting tension characteristics of the adult muscles were not affected by chemical skinning. From these results, we conclude that in rats resting muscle tension, like active tension, differentiates within the first 3 wk after birth.
Contribution of mono- and biarticular muscles to extending knee joint moments in runners and cyclists
Authors: Savelberg H. H. C. M. , Meijer K.
Published: March 2015

Motor actions are governed by coordinated activation of mono- and biarticular muscles. This study considered differences in mono- and biarticular knee extensors between runners and cyclists in the context of adaptations to task-specific movement requirements. Two hypotheses were tested: 1) the length-at-use hypothesis, which is that muscle adapts to have it operate around optimal length; and 2) the contraction-mode hypothesis, which is that eccentrically active muscles prefer to operate on the ascending limb of the length-force curve. Ten runners and ten cyclists performed maximal, isometric knee extensions on a dynamometer at five knee and four hip joint angles. This approach allowed the separation of the contribution of mono- and biarticular extensors. Three major differences occurred: 1) compared with runners, monoarticular extensors of cyclists reach optimal length at larger muscle length; 2) in runners, optimal length of the biarticular extensor is shifted to larger lengths; and 3) the moment generated by monoarticular extensor was larger in cyclists. Mono- and biarticular extensors respond to different adaptation triggers in runners and cyclists. Monoarticular muscles seem to adapt to the length-at-use, whereas biarticular muscles were found to be sensitive to the contraction-mode hypothesis.