bluuebunny/crossref_metadata_2025 huggingface dataset:
Thixotropy of rib cage respiratory muscles in normal subjects
Authors: Homma Ikuo , Hagbarth Karl-Erik
Published: December 2017

In this study, we searched for signs of thixotropic behavior in human rib cage respiratory muscles. If rib cage respiratory muscles possess thixotropic properties similar to those seen in other skeletal muscles in animals and humans, we expect resting rib cage circumference would be temporarily changed after deep rib cage inflations or deflations and that these aftereffects would be particularly pronounced in trials that combine conditioning deep inflations or deflations with forceful isometric contractions of the respiratory muscles. We used induction plethysmography to obtain a continuous relative measure of rib cage circumference changes during quiet breathing in 12 healthy subjects. Rib cage position at the end of the expiratory phase (EEP) was used as an index of resting rib cage circumference. Comparisons were made between EEP values of five spontaneous breaths immediately before and after six types of conditioning maneuvers: deep inspiration (DI); deep expiration (DE); DI combined with forceful effort to inspire (FII) or expire (FEI); and DE combined with forceful effort to inspire (FIE) or expire (FEE), both with temporary airway occlusion. The aftereffects of the conditioning maneuvers on EEP values were consistent with the supposition that human respiratory muscles possess thixotropic properties. EEP values were significantly enhanced after all conditioning maneuvers involving DI, and the aftereffects were particularly pronounced in the FII and FEI trials. In contrast, EEP values were reduced after DE maneuvers. The aftereffects were statistically significant for the FEE and FIE, but not DE, trials. It is suggested that respiratory muscle thixotropy may contribute to the pulmonary hyperinflation seen in patients with chronic obstructive pulmonary disease.
Distribution of pulmonary ventilation using Xe-enhanced computed tomography in prone and supine dogs
Authors: Marcucci Catherine , Nyhan Daniel , Simon Brett A.
Published: December 2017

Xe-enhanced computed tomography (CT; Xe-CT) is a method for the noninvasive measurement of regional pulmonary ventilation in intact subjects, determined from the washin and washout rates of the radiodense, nonradioactive gas Xe, as measured in serial CT scans. We used the Xe-CT ventilation method, along with other quantitative CT measurements, to investigate the distribution of regional lung ventilation and air content in healthy, anesthetized, mechanically ventilated dogs in the prone and supine postures. Vertical gradients in regional ventilation and air content were measured in five mongrel dogs in both prone and supine postures at four axial lung locations. In the supine position, ventilation increased with dependent location, with a mean slope of 7.3%/cm lung height, whereas no ventilation gradients were found at any location in the prone position. These results agree quantitatively with other published studies. In addition, six different animals were studied (3 supine, 3 prone) to examine the longitudinal distribution of ventilation and air content. The prone lungs were more uniformly inflated compared with the supine, which were less well expanded at the base than apex. Ventilation index, a measure of regional ventilation relative to whole lung ventilation, increased steeply from apex to base in the supine animals, whereas it was again more uniform in the prone condition. We conclude that the Xe-CT method provides a reasonable, quantitative measurement of regional ventilation and promises to be a valuable tool for the noninvasive determination of regional lung function.
The lung diffusing capacity for nitric oxide in rats is increased during endotoxemia
Authors: Stitt John T. , DuBois Arthur B.
Published: December 2017

Rats, when injected with endotoxin, begin to exhale nitric oxide (NO) within 1 h. This study measured the diffusing capacity for NO in the lungs of rats (Dl NO) under both control and endotoxemic conditions, and it also estimated the rate at which endogenous NO (V˙p NO) enters the distal compartment of the lung, both in control rats and during endotoxemia. Dl NO increased from 0.68 ± 0.12 (SE) ml · min−1 · mmHg−1 in control rats to 1.17 ± 0.25 ml · min−1 · mmHg−1 in endotoxemic rats. V˙p NO was 2.6 ± 0.5 nl/min in control rats and attained a value of 218.6 ± 50.1 nl/min at the height of NO exhalation 3 h after the endotoxin. We suggest that increased Dl NO reflects an increase in pulmonary membrane diffusing capacity, caused by a pulmonary hypertension that is due to neutrophil aggregation in the lung capillaries. Dl NO may also be increased by an enlarged pulmonary capillary volume because of the vasodilatory effects of the endogenous NO that is produced by the lung in response to the endotoxin. NO production by the lungs in response to endotoxin is unique in that it is the only situation reported to date in which pathologically induced increases in NO exhalation originate from the alveolar compartment of the lung, as opposed to the small conducting airways.
Effects of hypercapnia and hypocapnia on [Ca2+]imobilization in human pulmonary artery endothelial cells
Authors: Nishio Kazumi , Suzuki Yukio , Takeshita Kei , Aoki Takuya , Kudo Hiroyasu , Sato Nagato , Naoki Katsuhiko , Miyao Naoki , Ishii Makoto , Yamaguchi Kazuhiro
Published: December 2017

The hydrogen ion is an important factor in the alteration of vascular tone in pulmonary circulation. Endothelial cells modulate vascular tone by producing vasoactive substances such as prostacyclin (PGI2) through a process depending on intracellular Ca2+concentration ([Ca2+]i). We studied the influence of CO2-related pH changes on [Ca2+]iand PGI2production in human pulmonary artery endothelial cells (HPAECs). Hypercapnic acidosis appreciably increased [Ca2+]ifrom 112 ± 24 to 157 ± 38 nmol/l. Intracellular acidification at a normal extracellular pH increased [Ca2+]icomparable to that observed during hypercapnic acidosis. The hypercapnia-induced increase in [Ca2+]iwas unchanged by the removal of Ca2+from the extracellular medium or by the depletion of thapsigargin-sensitive intracellular Ca2+stores. Hypercapnic acidosis may thus release Ca2+from pH-sensitive but thapsigargin-insensitive intracellular Ca2+stores. Hypocapnic alkalosis caused a fivefold increase in [Ca2+]icompared with hypercapnic acidosis. Intracellular alkalinization at a normal extracellular pH did not affect [Ca2+]i. The hypocapnia-evoked increase in [Ca2+]iwas decreased from 242 ± 56 to 50 ± 32 nmol/l by the removal of extracellular Ca2+. The main mechanism affecting the hypocapnia-dependent [Ca2+]iincrease was thought to be the augmented influx of extracellular Ca2+mediated by extracellular alkalosis. Hypercapnic acidosis caused little change in PGI2production, but hypocapnic alkalosis increased it markedly. In conclusion, both hypercapnic acidosis and hypocapnic alkalosis increase [Ca2+]iin HPAECs, but the mechanisms and pathophysiological significance of these increases may differ qualitatively.
Blood-brain barrier permeability during dopamine-induced hypertension in fetal sheep
Authors: Harris Andrew P. , Robinson Roderick , Koehler Raymond C. , Traystman Richard J. , Gleason Christine A.
Published: December 2017

Dopamine is often used as a pressor agent in sick newborn infants, but an increase in arterial blood pressure could disrupt the blood-brain barrier (BBB), especially in the preterm newborn. Using time-dated pregnant sheep, we tested the hypothesis that dopamine-induced hypertension increases fetal BBB permeability and cerebral water content. Barrier permeability was assessed in nine brain regions, including cerebral cortex, caudate, thalamus, brain stem, cerebellum, and spinal cord, by intravenous injection of the small tracer molecule [14C]aminoisobutyric acid at 10 min after the start of dopamine or saline infusion. We studied 23 chronically catheterized fetal sheep at 0.6 (93 days, n = 10) and 0.9 (132 days, n = 13) gestation. Intravenous infusion of dopamine increased mean arterial pressure from 38 ± 3 to 53 ± 5 mmHg in 93-day fetuses and from 55 ± 5 to 77 ± 8 mmHg in 132-day fetuses without a decrease in arterial O2content. These 40% increases in arterial pressure are close to the maximum hypertension reported for physiological stresses at these ages in fetal sheep. No significant increases in the brain transfer coefficient of aminoisobutyric acid were detected in any brain region in dopamine-treated fetuses compared with saline controls at 0.6 or 0.9 gestation. There was also no significant increase in cortical water content with dopamine infusion at either age. We conclude that a 40% increase in mean arterial pressure during dopamine infusion in normoxic fetal sheep does not produce substantial BBB disruption or cerebral edema even as early as 0.6 gestation.
Analysis of tracheal mechanics and applications
Authors: Holzhäuser Ulrich , Lambert Rodney K.
Published: December 2017

We have developed a mathematical model for a tracheal ring that consists of a “horseshoe” of cartilage with its tips joined by a membrane. The ring is subjected to a uniform transmural pressure (Ptm) difference. The model was used to calculate the cross-sectional area ( A) of the trachea. Whereas the mechanics of the deformation of the cartilage were analyzed using elastica theory, the posterior membrane was treated as a simple membrane that is inextensible under changes in Ptm. The membrane can be specified to be of any length less than baseline and thus can represent a posterior membrane under tension. The cartilage can have specifiable nonuniform unstressed curvature as well as nonuniform bending stiffness. We have investigated the effect on the tracheal A-Ptm curve of posterior membrane length and tensile force in the membrane, cartilage shape and elasticity, and localized weakening of the cartilage. The model predictions are in good agreement with magnetic resonance imaging data from rabbit tracheas and show that the shape of the horseshoe as well as the posterior membrane force are important determinants of tracheal compliance.
Selected Contribution: NO released to flow reduces myogenic tone of skeletal muscle arterioles by decreasing smooth muscle Ca2+sensitivity
Authors: Ungvari Zoltan , Koller Akos
Published: December 2017

To clarify the contribution of intracellular Ca2+concentration ([Ca2+]i)-dependent and -independent signaling mechanisms in arteriolar smooth muscle (aSM) to modulation of arteriolar myogenic tone by nitric oxide (NO), released in response to increases in intraluminal flow from the endothelium, changes in aSM [Ca2+]iand diameter of isolated rat gracilis muscle arterioles (pretreated with indomethacin) were studied by fluorescent videomicroscopy. At an intraluminal pressure of 80 mmHg, [Ca2+]isignificantly increased and myogenic tone developed in response to elevations of extracellular Ca2+concentration. The Ca2+channel inhibitor nimodipine substantially decreased [Ca2+]iand completely inhibited myogenic tone. Dilations to intraluminal flow (that were inhibited by Nω-nitro-l-arginine methyl ester) or dilations to the NO donor S-nitroso- N-acetyl-dl-penicillamine (that were inhibited by the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one) were not accompanied by substantial decreases in aSM [Ca2+]i. 8-Bromoguanosine cGMP and the cGMP-specific phosphodiesterase inhibitor zaprinast significantly dilated arterioles yet elicited only minimal decreases in [Ca2+]i. Thus flow-induced endothelial release of NO elicits relaxation of arteriolar smooth muscle by a cGMP-dependent decrease of the Ca2+sensitivity of the contractile apparatus without substantial changes in the pressure-induced level of [Ca2+]i.
Selective muscle hypertrophy, changes in EMG and force, and serum hormones during strength training in older women
Authors: Häkkinen Keijo , Pakarinen Arto , Kraemer William J. , Häkkinen Arja , Valkeinen Heli , Alen Markku
Published: December 2017

Effects of strength training (ST) for 21 wk were examined in 10 older women (64 ± 3 yr). Electromyogram, maximal isometric force, one-repetition maximum strength, and rate of force development of the leg extensors, muscle cross-sectional area (CSA) of the quadriceps femoris (QF) and of vastus lateralis (VL), medialis (VM), intermedius (VI) and rectus femoris (RF) throughout the lengths of 3/12–12/15 (Lf) of the femur, muscle fiber proportion and areas of types I, IIa, and IIb of the VL were evaluated. Serum hormone concentrations of testosterone, growth hormone (GH), cortisol, and IGF-I were analyzed for the resting, preexercise, and postexercise conditions. After the 21-wk ST, maximal force increased by 37% ( P < 0.001) and 1-RM by 29% ( P < 0.001), accompanied by an increase ( P < 0.01) in rate of force development. The integrated electromyograms of the vastus muscles increased ( P < 0.05). The CSA of the total QF increased ( P < 0.05) throughout the length of the femur by 5–9%. The increases were significant ( P< 0.05) at 7/15–12/15 Lf for VL and at 3/15–8/15 Lf for VM, at 5/15–9/15 for VI and at 9/15 ( P < 0.05) for RF. The fiber areas of type I ( P < 0.05), IIa ( P < 0.001), and IIb ( P < 0.001) increased by 22–36%. No changes occurred during ST in serum basal concentrations of the hormones examined, but the level of testosterone correlated with the changes in the CSA of the QF ( r = 0.64, P < 0.05). An acute increase of GH ( P < 0.05), remaining elevated up to 30 min ( P < 0.05) postloading, was observed only at posttraining. Both neural adaptations and the capacity of skeletal muscle to undergo training-induced hypertrophy even in older women explain the strength gains. The increases in the CSA of the QF occurred throughout its length but differed selectively between the individual muscles. The serum concentrations of hormones remained unaltered, but a low level of testosterone may be a limiting factor in training-induced muscle hypertrophy. The magnitude and time duration of the acute GH response may be important physiological indicators of anabolic adaptations during strength training even in older women.
Neck muscle vibration disrupts steering of locomotion
Authors: Bove Marco , Diverio Manuela , Pozzo Thierry , Schieppati Marco
Published: December 2017

Neck muscle vibration was applied to human subjects to assess the influences of neck abnormal proprioceptive input on the organization and execution of gait. Subjects walked blindfolded to a previously seen target, located straight ahead at ∼4 m. Vibration was applied on the right side of the neck, both during and before walking. The variables measured were length, duration, and velocity of trajectory; relative and absolute frontal errors at target; and width of walking support base. Vibration applied during locomotion produced an undershoot of target and deviation of gait trajectory toward the side opposite to vibration. Vibration applied before locomotion produced no effect on length of trajectory but slowing of velocity and nonsystematic deviation. When vibration frequency was increased, the amplitude of the nonsystematic deviation increased. Vibration applied during or before stance trials had minor effects on body sway. Vibration before stance had no effect on the position of mean center of foot pressure, whereas vibration during stance displaced it to the side opposite to the vibrated muscle. We suggest that vibration during locomotion reduces length and velocity of trajectory because of a direct action on the locomotor centers and produces trajectory deviation related to its effect on stance. Vibration before locomotion causes a major, nonsystematic deviation from the planned trajectory, possibly connected to a disorientation of the internal references.
Hysteresivity of the lung and tissue strip in the normal rat: effects of heterogeneities
Authors: Sakai Hiroaki , Ingenito Edward P. , Mora Rene , Abbay Senay , Cavalcante Francisco S. A. , Lutchen Kenneth R. , Suki Béla
Published: December 2017

We measured lung impedance in rats in closed chest (CC), open chest (OC), and isolated lungs (IL) at four transpulmonary pressures with a optimal ventilator waveform. Data were analyzed with an homogeneous linear or an inhomogeneous linear model. Both models include tissue damping and elastance and airway inertance. The homogeneous linear model includes airway resistance (Raw), whereas the inhomogeneous linear model has a continuous distribution of Raw characterized by the mean Raw and the standard deviation of Raw (SDR). Lung mechanics were compared with tissue strip mechanics at frequencies and operating stresses comparable to those during lung impedance measurements. The hysteresivity (η) was calculated as tissue damping/elastance. We found that 1) airway and tissue parameters were different in the IL than in the CC and OC conditions; 2) SDR was lowest in the IL; and 3) η in IL at low transpulmonary pressure was similar to η in the tissue strip. We conclude that η is primarily determined by lung connective tissue, and its elevated estimates from impedance data in the CC and OC conditions are a consequence of compartment-like heterogeneity being greater in CC and OC conditions than in the IL.
Historical perspective on airway smooth muscle: the saga of a frustrated cell
Authors: Seow C. Y. , Fredberg J. J.
Published: December 2017

Despite the lack of a clearly defined physiological function, airway smooth muscle receives substantial attention because of its involvement in the pathogenesis of asthma. Recent investigations have turned to the ways in which the muscle is influenced by its dynamic microenvironment. Ordinarily, airway smooth muscle presents little problem, even when maximally activated, because unending mechanical perturbations provided by spontaneous tidal breathing put airway smooth muscle in a perpetual state of “limbo,” keeping its contractile machinery off balance and unable to achieve its force-generating potential. The dynamic microenvironment affects airway smooth muscle in at least two ways: by acute changes associated with disruption of myosin binding and by chronic changes associated with plastic restructuring of contractile and cytoskeletal filament organization. Plastic restructuring can occur when dynamic length changes occur between sequential contractile events or within a single contractile event. Impairment of these normal responses of airway smooth muscle to its dynamic environment may be implicated in airway hyperresponsiveness in asthma.
Skeletal muscle capillarity and angiogenic mRNA levels after exercise training in normoxia and chronic hypoxia
Authors: Olfert I. Mark , Breen Ellen C. , Mathieu-Costello Odile , Wagner Peter D.
Published: December 2017

Gene expression of vascular endothelial growth factor (VEGF), and to a lesser extent of transforming growth factor-β1 (TGF-β1) and basic fibroblast growth factor (bFGF), has been found to increase in rat skeletal muscle after a single exercise bout. In addition, acute hypoxia augments the VEGF mRNA response to exercise, which suggests that, if VEGF is important in muscle angiogenesis, hypoxic training might produce greater capillary growth than normoxic training. Therefore, we examined the effects of exercise training (treadmill running at the same absolute intensity) in normoxia and hypoxia (inspired O2 fraction = 0.12) on rat skeletal muscle capillarity and on resting and postexercise gene expression of VEGF, its major receptors (flt-1 and flk-1), TGF-β1, and bFGF. Normoxic training did not alter basal or exercise-induced VEGF mRNA levels but produced a modest twofold increase in bFGF mRNA ( P < 0.05). Rats trained in hypoxia exhibited an attenuated VEGF mRNA response to exercise (1.8-fold compared 3.4-fold with normoxic training; P< 0.05), absent TGF-β1 and flt-1 mRNA responses to exercise, and an approximately threefold ( P < 0.05) decrease in bFGF mRNA levels. flk-1 mRNA levels were not significantly altered by either normoxic or hypoxic training. An increase in skeletal muscle capillarity was observed only in hypoxically trained rats. These data show that, whereas training in hypoxia potentiates the adaptive angiogenic response of skeletal muscle to a given absolute intensity of exercise, this was not evident in the gene expression of VEGF or its receptors when assessed at the end of training.
Airway stability and heterogeneity in the constricted lung
Authors: Anafi Ron C. , Wilson Theodore A.
Published: December 2017

The effect of bronchoconstriction on airway resistance is known to be spatially heterogeneous and dependent on tidal volume. We present a model of a single terminal airway that explains these features. The model describes a feedback between flow and airway resistance mediated by parenchymal interdependence and the mechanics of activated smooth muscle. The pressure-tidal volume relationship for a constricted terminal airway is computed and shown to be sigmoidal. Constricted terminal airways are predicted to have two stable states: one effectively open and one nearly closed. We argue that the heterogeneity of whole lung constriction is a consequence of this behavior. Airways are partitioned between the two states to accommodate total flow, and changes in tidal volume and end-expiratory pressure affect the number of airways in each state. Quantitative predictions for whole lung resistance and elastance agree with data from previously published studies on lung impedance.
Glucose uptake and metabolic stress in rat muscles stimulated electrically with different protocols
Authors: Aslesen Rune , Engebretsen Ellen M. L. , Franch Jesper , Jensen Jørgen
Published: December 2017

In the present study, the relationship between the pattern of electrical stimulation and glucose uptake was investigated in slow-twitch muscles (soleus) and fast-twitch muscles (epitrochlearis) from Wistar rats. Muscles were stimulated electrically for 30 min in vitro with either single pulses (frequencies varied between 0.8 and 15 Hz) or with 200-ms trains (0.1–2 Hz). Glucose uptake (measured with tracer amount of 2-[3H]deoxyglucose) increased with increasing number of impulses whether delivered as single pulses or as short trains. The highest glucose uptake achieved with short tetanic contractions was similar in soleus and epitrochlearis (10.9 ± 0.7 and 12.0 ± 0.8 mmol · kg dry wt−1· 30 min−1, respectively). Single pulses, on the other hand, increased contraction-stimulated glucose uptake less in soleus than in epitrochlearis (7.5 ± 1.1 and 11.7 ± 0.5 mmol · kg dry wt−1· 30 min−1, respectively; P < 0.02). Glucose uptake correlated with glycogen breakdown in soleus ( r = 0.84, P < 0.0001) and (epitrochlearis: r = 0.91, P < 0.0001). Contraction-stimulated glucose uptake also correlated with breakdown of ATP and PCr and with reduction in force. Our data suggest that metabolic stress mediates contraction-stimulated glucose uptake.
Genetic selection of mice for high voluntary wheel running: effect on skeletal muscle glucose uptake
Authors: Dumke C. L. , Rhodes J. S. , Garland T. , Maslowski E. , Swallow J. G. , Wetter A. C. , Cartee G. D.
Published: December 2017

Effects of genetic selection for high wheel-running activity (17th generation) and access to running wheels on skeletal muscle glucose uptake were studied in mice with the following treatments for 8 wk: 1) access to unlocked wheels; 2) same as 1, but wheels locked 48 h before glucose uptake measurement; or 3) wheels always locked. Selected mice ran more than random-bred (nonselected) mice (8-wk mean ± SE = 8,243 ± 711 vs. 3,719 ± 233 revolutions/day). Body weight was 5–13% lower for selected vs. nonselected groups. Fat pad/body weight was ∼40% lower for selected vs. nonselected and unlocked vs. locked groups. Insulin-stimulated glucose uptake and fat pad/body weight were inversely correlated for isolated soleus ( r = −0.333; P < 0.005) but not extensor digitorum longus (EDL) or epitrochlearis muscles. Insulin-stimulated glucose uptake was higher in EDL ( P < 0.02) for selected vs. nonselected mice. Glucose uptake did not differ by wheel group, and amount of running did not correlate with glucose uptake for any muscle. Wheel running by mice did not enhance subsequent glucose uptake by isolated muscles.
Selected Contribution: Synergism between TNF-α and IL-1β in airway smooth muscle cells: implications for β-adrenergic responsiveness
Authors: Moore Paul E. , Lahiri Thomas , Laporte Johanne D. , Church Trudi , Panettieri Reynold A. , Shore Stephanie A.
Published: December 2017

In human cultured airway smooth muscle cells, interleukin (IL)-1β increases cyclooxygenase (COX)-2 expression and PGE2release, ultimately resulting in decreased β-adrenergic responsiveness. In this study, we aimed to determine whether tumor necrosis factor-α (TNF-α) synergizes with IL-1β in the induction of these events. TNF-α alone, at concentrations up to 10 ng/ml, had no effect on COX-2 protein expression; at concentrations as low as 0.1 ng/ml, it significantly enhanced the ability of IL-1β (0.2 ng/ml) to induce COX-2 and to increase PGE2release. IL-1β and TNF-α in combination also significantly enhanced COX-2 promoter activity, indicating that synergism between the cytokines is mediated at the level of gene transcription. Although IL-1β and TNF-α each increased nuclear factor-κB activation and induced extracellular regulated kinase and p38 phosphorylation, combined administration of the cytokines did not enhance either nuclear factor-κB or mitogen-activated protein kinase activation. Combined administration of IL-1β (0.2 ng/ml) and TNF-α (0.1 or 1.0 ng/ml) reduced the ability of isoproterenol to decrease human airway smooth muscle cell stiffness, as measured by magnetic twisting cytometry, even though individually these cytokines, at these concentrations, had no effect on isoproterenol responses. Treatment with the selective COX-2 inhibitor NS-398 abolished the synergistic effects of TNF-α and IL-1β on β-adrenergic responsiveness. Our results indicate that low concentrations of IL-1β and TNF-α synergize to promote β-adrenergic hyporesponsiveness and that effects on COX-2 expression and PGE2are responsible for these events. The data suggest that the simultaneous release in the airway, of even very small amounts of cytokines, can have important functional consequences.
Analysis of the harmonic content of the tidal flow waveforms in infants
Authors: Frey Urs , Silverman Michael , Suki Bela
Published: December 2017

The aim of this study was to examine whether the spectral characteristics of tidal flow waveform reflect the interaction between the control of breathing and lung mechanics in 10 healthy infants (H), 10 infants with a history of wheezing disorders (W), and 10 infants with chronic lung disease (CLD). From the flow waveform, we calculated a shape index, the harmonic distortion ( k d), which quantifies the extent to which a periodic signal deviates from a sine wave. The k d of the entire tidal flow waveform did not significantly discriminate between diagnostic groups. However, k d was sensitive to maturation: it increased from 0.26 at 1 mo to 0.37 at 6 mo of age ( P < 0.002). Furthermore, the frequency ( f) spectra of the flow (V˙) amplitudes between 0.13 and 10 Hz followed a power law:V˙( f) ∼ f − s , where s(slope) is the exponent in the power law. The exponent of the healthy infants s(H) was 4.24 [95% confidence interval (CI) = 0.2] at 1 mo, 4.39 (CI = 0.16) at 6 mo, and 4.35 (CI = 0.19) at 12 mo and not significantly changing with age. The mean value of s(W) was marginally lower (4.09 ± 0.28; P < 0.05) than that of s(H). The mean s(CLD) was significantly lower (3.04 ± 0.31; P < 0.001). Lower values of s and higher values of k d indicate an increased complexity of the feedback mechanisms determining tidal flow waveform and may be associated with disease.
Reduction in hybrid single muscle fiber proportions with resistance training in humans
Authors: Williamson D. L. , Gallagher P. M. , Carroll C. C. , Raue U. , Trappe S. W.
Published: December 2017

The purpose of this investigation was to examine the effects of 12 wk of progressive resistance training (PRT) on single muscle fiber myosin heavy chain (MHC; I, I/IIa, I/IIa/IIx, IIa, IIa/IIx, IIx) isoform proportions in young individuals. Young, untrained men (YM; n = 6) and women (YW; n = 6) (age = 22 ± 1 and 25 ± 2 yr for YW and YM, respectively) received pre- and post-PRT muscle biopsies from the right vastus lateralis for single muscle fiber MHC distribution by electrophoretic analysis (192 ± 5 pre- and 183 ± 6 post-fibers/subject analyzed; 4,495 fibers total). Data are presented as percentages of the total fibers analyzed per subject. The PRT protocol elicited an increase in the pure MHC IIa (Δ = + 24 and + 27; YW and YM, respectively; P < 0.05) with no change in the pure MHC I distribution. The hybrid MHC distributions decreased I/IIa/IIx (Δ = −2; YM and YW; P < 0.05), IIa/IIx (Δ = −13 and −19 for YM and YW, respectively; P < 0.05), and total hybrid fiber proportion (I/IIa + I/IIa/IIx + IIa/IIx) decreased (Δ = −19 and −30 for YM and YW, respectively; P < 0.05) with the training, as did the MHC IIx distribution (Δ = −2; YW only; P < 0.05). Alterations in the predominance of MHC isoforms within hybrid fibers (decrease in MHC I-dominant I/IIa and nondominant MHC IIa/IIx, increase in MHC IIa-dominant IIa/IIx; P < 0.05) appeared to contribute to the increase in the MHC IIa proportion. Electrophoresis of muscle cross sections revealed an ∼7% increase ( P< 0.05) in MHC IIa proportion in both groups, whereas the MHC IIx decrease by 7.5 and 11.6% post-PRT in YW and YM, respectively. MHC I proportions increase in YM by 4.8% ( P < 0.05) post-PRT. These findings further support previous resistance training data in young adults with respect to the increase in the MHC IIa proportions but demonstrate that a majority of the change can be attributed to the decrease in single-fiber hybrid proportions.
Effects of tidal volume stretch on airway constriction in vivo
Authors: Brown Robert , Mitzner Wayne
Published: December 2017

Tidal stresses are thought to be involved in maintaining airway patency in vivo. The present study examined the effects of normal stresses exerted by the lung parenchyma during tidal ventilation on recovery from agonist-induced airway constriction. In seven anesthetized dogs, one lung was selectively ventilated with a Univent endotracheal tube (Vitaid, Lewiston, NY). Airway tone was increased either transiently (intravenous bolus) or continuously (intravenous infusion) with methacholine (MCh). During one-lung ventilation, changes in the airway size of both lungs were measured for up to 40 min during recovery from constriction by using high-resolution computed tomography. After recovery to baseline, the alternate lung was ventilated, and the protocol was repeated. The absence of tidal stresses led to an attenuated recovery from either transient or steady-state airway constriction. The effectiveness or lack thereof of normal tidal stress in stabilizing airway size may be one factor that contributes to the lack of reversal with tidal breathing and deep inspiration seen in asthmatic subjects.
Exercise-induced oxidative stress affects erythrocytes in sedentary rats but not exercise-trained rats
Authors: Şentürk Ümit Kemal , Gündüz Filiz , Kuru Oktay , Aktekin Mehmet R. , Kipmen Dijle , Yalçin Özlem , Bor-Küçükatay Melek , Yeşilkaya Akin , Başkurt Oğuz K.
Published: December 2017

Oxidant stress is one of the factors proposed to be responsible for damaged erythrocytes observed during and after exercise. The impact of exertional oxidant stress after acute exhaustive treadmill running on erythrocyte damage was investigated in sedentary (Sed) and exercise-trained (ET) rats treated with or without antioxidant vitamins C and E. Exhaustive exercise led to statistically significant increments in the levels of thiobarbituric acid-reactive substance (TBARS) and H2O2-induced TBARS in Sed rats and resulted in functional and structural alterations in erythrocytes (plasma hemoglobin concentrations, methemoglobin levels, and rise in osmotic fragility of erythrocytes with decrease in erythrocyte deformability). Administration of antioxidant vitamin for 1 mo before exhaustive exercises prevented lipid peroxidation (TBARS, H2O2-induced TBARS) in Sed rats without any functional or structural alterations in erythrocytes. Parameters indicating erythrocyte lipid peroxidation and deterioration after exhaustive exercise in rats trained regularly with treadmill running for 1 mo were not different from those in Sed controls. Erythrocyte lipid peroxidation (TBARS) increased in exhausted-ET rats compared with ET controls; however, the plasma hemoglobin, methemoglobin levels, and erythrocyte osmotic fragility and deformability did not differ. Exhaustive exercise-induced lipid peroxidation in ET rats on antioxidant vitamin treatment was prevented, whereas functional and structural parameters of erythrocytes were not different from those of the ET controls. We conclude that exertional oxidant stress contributed to erythrocyte deterioration due to exercise in Sed but not in ET rats.
Effects of vagal denervation on cardiorespiratory and behavioral responses in the newborn lamb
Authors: Lalani Salim , Remmers John E. , Green Francis H. , Bukhari Ashfaq , Ford Gordon T. , Hasan Shabih U.
Published: December 2017

Recently, Wong et al. (Wong KA, Bano A, Rigaux A, Wang B, Bharadwaj B, Schurch S, Green F, Remmers JE, and Hasan SU, J Appl Physiol 85: 849–859, 1998) demonstrated that fetal lambs that have undergone vagal denervation prenatally do not establish adequate alveolar ventilation shortly after birth. In their study, however, vagal denervation was performed prenatally and the deleterious effects of vagal denervation on breathing patterns and gas exchange could have resulted from the prenatal actions of the neurotomy. To quantify the relative roles of pre- vs. postnatal vagal denervation on control of breathing, we studied 14 newborn lambs; 6 were sham operated, and 8 were vagally denervated below the origin of the recurrent laryngeal nerve. Postoperatively, all denervated animals became hypoxemic and seven of eight succumbed to respiratory failure. In vagally denervated lambs, expiratory time increased, whereas respiratory rate, minute ventilation, and lung compliance decreased compared with the sham-operated animals. In the early postoperative period, the frequency of augmented breaths was lower but gradually increased over time in the denervated vs. sham-operated group. The dynamic functional residual capacity was significantly higher than the passive functional residual capacity among the sham-operated group compared with the denervated group. No significant differences were observed in the prevalence of various sleep states and in the amount of total phospholipids or large- and small-aggregate surfactants between the two groups. We provide new evidence indicating that intrauterine actions of denervation are not required to explain the effects of vagal denervation on postnatal survival. Our data suggest that vagal input is critical in the maintenance of normal breathing patterns, end-expiratory lung volume, and gas exchange during the early neonatal period.
Anorexic effect of K+channel blockade in mesenteric arterial smooth muscle and intestinal epithelial cells
Authors: McDaniel Sharon S. , Platoshyn Oleksandr , Yu Ying , Sweeney Michele , Miriel Victor A. , Golovina Vera A. , Krick Stefanie , Lapp Bethany R. , Wang Jian-Ying , Yuan Jason X.-J.
Published: December 2017

Activity of voltage-gated K+(Kv) channels controls membrane potential ( Em). Membrane depolarization due to blockade of K+channels in mesenteric artery smooth muscle cells (MASMC) should increase cytoplasmic free Ca2+concentration ([Ca2+]cyt) and cause vasoconstriction, which may subsequently reduce the mesenteric blood flow and inhibit the transportation of absorbed nutrients to the liver and adipose tissue. In this study, we characterized and compared the electrophysiological properties and molecular identities of Kv channels and examined the role of Kv channel function in regulating Emin MASMC and intestinal epithelial cells (IEC). MASMC and IEC functionally expressed multiple Kv channel α- and β-subunits (Kv1.1, Kv1.2, Kv1.3, Kv1.4, Kv1.5, Kv2.1, Kv4.3, and Kv9.3, as well as Kvβ1.1, Kvβ2.1, and Kvβ3), but only MASMC expressed voltage-dependent Ca2+channels. The current density and the activation and inactivation kinetics of whole cell Kv currents were similar in MASMC and IEC. Extracellular application of 4-aminopyridine (4-AP), a Kv-channel blocker, reduced whole cell Kv currents and caused Emdepolarization in both MASMC and IEC. The 4-AP-induced Emdepolarization increased [Ca2+]cytin MASMC and caused mesenteric vasoconstriction. Furthermore, ingestion of 4-AP significantly reduced the weight gain in rats. These results suggest that MASMC and IEC express multiple Kv channel α- and β-subunits. The function of these Kv channels plays an important role in controlling Em. The membrane depolarization-mediated increase in [Ca2+]cytin MASMC and mesenteric vasoconstriction may inhibit transportation of absorbed nutrients via mesenteric circulation and limit weight gain.
Bronchoprotective and bronchodilatory effects of deep inspiration in rabbits subjected to bronchial challenge
Authors: Gunst S. J. , Shen X. , Ramchandani R. , Tepper R. S.
Published: December 2017

The effect of deep inspiration (DI) on airway responsiveness differs in asthmatic and normal human subjects. The mechanism for the effects of DI on airway responsiveness in vivo has not been identified. To elucidate potential mechanisms, we compared the effects of DI imposed before or during induced bronchoconstriction on the airway response to methacholine (MCh) in rabbits. The changes in airway resistance in response to intravenous MCh were continuously monitored. DI depressed the maximum response to MCh when imposed before or during the MCh challenge; however, the inhibitory effect of DI was greater when imposed during bronchoconstriction. Because immature rabbits have greater airway reactivity than mature rabbits, we compared the effects of DI on their airway responses. No differences were observed. Our results suggest that the mechanisms by which DI inhibits airway responsiveness do not depend on prior activation of airway smooth muscle (ASM). These results are consistent with the possibility that reorganization of the contractile apparatus caused by stretch of ASM during DI contributes to depression of the airway response.
Activation of human quadriceps femoris during isometric, concentric, and eccentric contractions
Authors: Babault Nicolas , Pousson Michel , Ballay Yves , Van Hoecke Jacques
Published: December 2017

Maximal and submaximal activation level of the right knee-extensor muscle group were studied during isometric and slow isokinetic muscular contractions in eight male subjects. The activation level was quantified by means of the twitch interpolation technique. A single electrical impulse was delivered, whatever the contraction mode, on the femoral nerve at a constant 50° knee flexion (0° = full extension). Concentric, eccentric (both at 20°/s velocity), and isometric voluntary activation levels were then calculated. The mean activation levels during maximal eccentric and maximal concentric contractions were 88.3 and 89.7%, respectively, and were significantly lower ( P < 0.05) with respect to maximal isometric contractions (95.2%). The relationship between voluntary activation levels and submaximal torques was linearly fitted ( P < 0.01): comparison of slopes indicated lower activation levels during submaximal eccentric compared with isometric or concentric contractions. It is concluded that reduced neural drive is present during 20°/s maximal concentric and both maximal and submaximal eccentric contractions. These results indicate a voluntary activation dependency on both tension levels and type of muscular actions in the human knee-extensor muscle group.
Effect of aging on fatigue characteristics of elbow flexor muscles during sustained submaximal contraction
Authors: Bilodeau Martin , Henderson Tara K. , Nolta Brian E. , Pursley Paul J. , Sandfort Gretchen L.
Published: December 2017

The purpose of this study was to compare fatigue-related measures of central and peripheral mechanisms between young and elderly subjects for a task performed with elbow flexor muscles. Ten young and nine elderly subjects performed a sustained submaximal fatigue task at 35% of their maximum voluntary contraction torque. Measures of neuromuscular function, reflecting changes in neuromuscular propagation, voluntary activation, excitation-contraction-relaxation processes, and metabolite buildup, were taken before, during, and after the fatigue task. The main results were the absence of neuromuscular propagation failure in either young or elderly subjects, the presence of central fatigue at the end of the fatigue task in 7 of 9 elderly but only 3 of 10 young subjects, and lesser changes in twitch torque contraction-relaxation variables and electromyographic median frequency in elderly compared with young subjects. The lesser fatigue-related changes in twitch contraction speed and median frequency in elderly compared with young subjects could reflect the increase in type I-to-type II fiber area reported with old age. The presence of significant central fatigue can apparently minimize some of the potential differences present in peripheral fatigue sites.
Flowmetric comparison of respiratory inductance plethysmography and pneumotachography in horses
Authors: Hoffman Andrew , Kuehn Heike , Riedelberger Klaus , Kupcinskas Rachel , Miskovic Mary Beth
Published: December 2017

Respiratory inductance plethysmographic (RIP) and pneumotachographic (Pn) flows were compared dynamically in horses with bronchoconstriction. On a breath-by-breath basis, RIP was normalized to inspiratory volume from Pn, and peak [peak of subtracted final exhalation waveform (SFEmax)] and selected area [integral of subtracted final waveform during first 25% of exhaled volume (SFEint)] differences between RIP and Pn flows during early expiration were measured in three settings: 1) healthy horses ( n = 8) undergoing histamine bronchoprovocation; 2) horses with naturally occurring lower airway obstruction (AO) ( n = 7); and 3) healthy horses ( n = 6) given lobeline · HCl to induce hyperpnea. In setting 1, histamine challenge induced a dose-dependent increase in SFEmaxand SFEintdifferences. A test index of airway reactivity (interpolated histamine dose that increased SFEmaxby 35%) closely correlated ( rs= 0.93, P = 0.001) with a conventional index (histamine dose that induced a 35% decrease in dynamic compliance). In setting 2, in horses with AO, SFEmaxand SFEintwere markedly elevated, and their absolute values correlated significantly ( P < 0.005) with pulmonary resistance and the maximum change in transpulmonary pressure. The effects of bronchodilator treatment on the SFEmaxand SFEintwere also highly significant ( P < 0.0001). In setting 3, hyperpnea, but not tachypnea, caused significant ( P < 0.01) increases in SFEmaxbut not in SFEint. In conclusion, dynamic comparisons between RIP and Pn provide a defensible method for quantifying AO during tidal breathing, without the need for invasive instrumentation.
Dopaminergic modulation of ventilation in obese Zucker rats
Authors: Nakano Hitoshi , Lee Shin-Da , Farkas Gaspar A.
Published: December 2017

To investigate the hypothesis that the impaired respiratory drive noted in morbid obesity was attributable to altered dopaminergic mechanisms acting on peripheral and/or central chemoreflex sensitivity, seven obese and seven lean Zucker rats were studied at 11 wk of age. Ventilation (V˙e) was measured by the barometric technique during hyperoxic (100% O2), normoxic (21% O2), hypoxic (10% O2), and hypercapnic (7% CO2) exposures after the administration of vehicle (control), haloperidol [Hal, 1 mg/kg, a central and peripheral dopamine (Da) receptor antagonist], or domperidone (Dom, 0.5 mg/kg, a peripheral Da receptor antagonist). In both lean and obese rats, Hal increased tidal volume and decreased respiratory frequency during hyperoxia or normoxia, resulting in an unchanged V˙e. In contrast, Dom did not affect tidal volume, frequency, orV˙e during hyperoxia or normoxia. During hypoxia, however, V˙e significantly increased from 1,132 ± 136 to 1,348 ± 98 ml · kg−1 · min−1( P < 0.01) after the administration of Dom in obese rats, whereas no change was observed in lean rats. Hal significantly decreased V˙e during hypoxia compared with control in lean but not obese rats. In both lean and obese rats, Hal decreasedV˙e in response to hypercapnia, whereas Dom had no effect. Our major findings suggest that peripheral chemosensitivity to hypoxia in obese Zucker rats is reduced as a result of an increased dopaminergic receptor modulation in the carotid body.
Neural responses to intravenous serotonin revealed by functional magnetic resonance imaging
Authors: Henderson Luke A. , Yu Pearl L. , Frysinger Robert C. , Galons Jean-Philippe , Bandler Richard , Harper Ronald M.
Published: December 2017

We examined the sequence of neural responses to the hypotension, bradycardia, and apnea evoked by intravenous administration of 5-hydroxytryptamine (serotonin). Functional magnetic resonance imaging signal changes were assessed in nine isoflurane-anesthetized cats during baseline and after a bolus intravenous low dose (10 μg/kg) or high dose (20–30 μg/kg) of 5-hydroxytryptamine. In all cats, high-dose challenges elicited rapid-onset, transient signal declines in the intermediate portion of the solitary tract nucleus, caudal midline and caudal and rostral ventrolateral medulla, and fastigial nucleus of the cerebellum. Slightly delayed phasic declines appeared in the dentate and interpositus nuclei and dorsolateral pons. Late-developing responses also emerged in the solitary tract nucleus, parapyramidal region, periaqueductal gray, spinal trigeminal nucleus, inferior olivary nucleus, cerebellar vermis, and fastigial nucleus. Amygdala and hypothalamic sites showed delayed and prolonged signal increases. Intravenous serotonin infusion recruits cerebellar, amygdala, and hypothalamic sites in addition to classic brain stem cardiopulmonary areas and exhibits site-specific temporal patterns.
Ca2+ release from ryanodine-sensitive store contributes to mechanism of hypoxic vasoconstriction in rat lungs
Authors: Morio Yoshiteru , McMurtry Ivan F.
Published: December 2017

Studies of thapsigargin, cyclopiazonic acid, and ryanodine in isolated pulmonary arteries and smooth muscle cells suggest that release of Ca2+ from inositol 1,4,5-trisphosphate (IP3)- and/or ryanodine-sensitive sarcoplasmic reticulum Ca2+ stores is a component of the mechanism of acute hypoxic pulmonary vasoconstriction (HPV). However, the actions of these agents on HPV in perfused lungs have not been reported. Thus we tested effects of thapsigargin and cyclopiazonic acid, inhibitors of sarcoplasmic reticulum Ca2+-ATPase, and of ryanodine, an agent that either locks the ryanodine receptor open or blocks it, on HPV in salt solution-perfused rat lungs. After inhibition of cyclooxygenase and nitric oxide synthase, thapsigargin (10 nM) and cyclopiazonic acid (5 μM) augmented the vasoconstriction to 0% but not to 3% inspired O2. Relatively high concentrations of ryanodine (100 and 300 μM) blunted HPV in nitric oxide synthase-inhibited lungs. The results indicate that release of Ca2+ from the ryanodine-sensitive, but not the IP3-sensitive, store, contributes to the mechanism of HPV in perfused rat lungs and that Ca2+-ATPase-dependent Ca2+ buffering moderates the response to severe hypoxia.