bluuebunny/crossref_metadata_2025 huggingface dataset:
A physiological level of clenbuterol does not prevent atrophy or loss of force in skeletal muscle of old rats
Authors: Chen Kuangjen D. , Alway Stephen E.
Published: December 2017

Supraphysiological levels of clenbuterol (CL) reduce muscle degradation in both young and old animals; however, these pharmacological levels induce side effects that are unacceptable in the elderly. In this study, we tested the hypothesis that a “physiological” dose of CL (10 μg · kg−1· day−1) would attenuate the loss of in situ isometric force and mass in muscles of senescent rats during hindlimb suspension (HS). Adult (3 mo) and senescent (38 mo) Fischer 344 × Brown Norway rats received CL or a placebo during 21 days of normal-weight-bearing or HS conditions (8 rats/age group). HS reduced soleus muscle weight-to-body weight ratio by 31%, muscle cross-sectional area by 37%, and maximal isometric tetanic force (Po) by 76% in senescent rats. CL attenuated the loss of Poand muscle weight by 17 and 8%, respectively, in the soleus of senescent rats relative to HS+placebo conditions, but it did not improve muscle weight normalized for body weight. CL did not reduce the decrease in soleus Poor mass after HS in adult rats. CL failed to reduce the loss of plantaris weight (−20%) and Po(−46%) in senescent rats after HS. Our data support the conclusion that physiological levels of CL do not improve fast muscle atrophy and only modestly reduce slow muscle atrophy, and, therefore, it is largely an ineffective countermeasure for preventing muscle wasting from HS in senescent rats.
Exercise-dependent growth hormone release is linked to markers of heightened central adrenergic outflow
Authors: Weltman Arthur , Pritzlaff Cathy J. , Wideman Laurie , Weltman Judy Y. , Blumer Jeffery L. , Abbott Robert D. , Hartman Mark L. , Veldhuis Johannes D.
Published: December 2017

To test the hypothesis that heightened sympathetic outflow precedes and predicts the magnitude of the growth hormone (GH) response to acute exercise (Ex), we studied 10 men [age 26.1 ± 1.7 (SE) yr] six times in randomly assigned order (control and 5 Ex intensities). During exercise, subjects exercised for 30 min (0900–0930) on each occasion at a single intensity: 25 and 75% of the difference between lactate threshold (LT) and rest (0.25LT, 0.75LT), at LT, and at 25 and 75% of the difference between LT and peak (1.25LT, 1.75LT). Mean values for peak plasma epinephrine (Epi), plasma norepinephrine (NE), and serum GH concentrations were determined [Epi: 328 ± 93 (SE), 513 ± 76, 584 ± 109, 660 ± 72, and 2,614 ± 579 pmol/l; NE: 2.3 ± 0.2, 3.9 ± 0.4, 6.9 ± 1.0, 10.7 ± 1.6, and 23.9 ± 3.9 nmol/l; GH: 3.6 ± 1.5, 6.6 ± 2.0, 7.0 ± 2.0, 10.7 ± 2.4, and 13.7 ± 2.2 μg/l for 0.25, 0.75, 1.0, 1.25, and 1.75LT, respectively]. In all instances, the time of peak plasma Epi and NE preceded peak GH release. Plasma concentrations of Epi and NE always peaked at 20 min after the onset of Ex, whereas times to peak for GH were 54 ± 6 (SE), 44 ± 5, 38 ± 4, 38 ± 4, and 37 ± 2 min after the onset of Ex for 0.25–1.75LT, respectively. ANOVA revealed that intensity of exercise did not affect the foregoing time delay between peak NE or Epi and peak GH (range 17–24 min), with the exception of 0.25LT ( P < 0.05). Within-subject linear regression analysis disclosed that, with increasing exercise intensity, change in (Δ) GH was proportionate to both ΔNE ( P = 0.002) and ΔEpi ( P = 0.014). Furthermore, within-subject multiple-regression analysis indicated that the significant GH increment associated with an antecedent rise in NE ( P = 0.02) could not be explained by changes in Epi alone ( P = 0.77). Our results suggest that exercise intensity and GH release in the human may be coupled mechanistically by central adrenergic activation.
Effects of desferrioxamine on serum erythropoietin and ventilatory sensitivity to hypoxia in humans
Authors: Ren Xiaohui , Dorrington Keith L. , Maxwell Patrick H. , Robbins Peter A.
Published: December 2017

In cell culture, hypoxia stabilizes a transcriptional complex called hypoxia-inducible factor-1 (HIF-1) that increases erythropoietin (Epo) formation. One hallmark of HIF-1 responses is that they can be induced by iron chelation. The first aim of this study was to examine whether an infusion of desferrioxamine (DFO) increased serum Epo in humans. If so, this might provide a paradigm for identifying other HIF-1 responses in humans. Consequently a second aim was to determine whether an infusion of DFO would mimic prolonged hypoxia and increase the acute hypoxic ventilatory response (AHVR). Sixteen volunteers undertook two protocols: 1) continuous infusion of DFO over 8 h and 2) control. Epo and AHVR were measured at fixed times during and after the protocols. The results show that 1) compared with control, Epo increased in most subjects at 8 h [52.8 ± 57.7 vs. 6.9 ± 2.5 (SD) mIU/ml, for DFO = 4 g/70 kg body wt, P < 0.05] and 12 h (63.7 ± 76.3 vs. 7.3 ± 2.5 mIU/ml, P < 0.001) after the start of DFO administration and 2) DFO had no significant effect on AHVR. We conclude that, whereas infusions of DFO mimic hypoxia by increasing Epo, they do not mimic prolonged hypoxia by augmenting AHVR.
Pulmonary blood flow remains fractal down to the level of gas exchange
Authors: Glenny Robb W. , Bernard Susan L. , Robertson H. Thomas
Published: December 2017

The spatial distribution of pulmonary blood flow is increasingly heterogeneous as progressively smaller lung regions are examined. To determine the extent of perfusion heterogeneity at the level of gas exchange, we studied blood flow distributions in rat lungs by using an imaging cryomicrotome. Approximately 150,000 fluorescent 15-μm-diameter microspheres were injected into tail veins of five awake rats. The rats were heavily anesthetized; the lungs were removed, filled with an optimal cutting tissue compound, and frozen; and the spatial location of every microsphere was determined. The data were mathematically dissected with the use of an unbiased random sampling method. The coefficients of variation of microsphere distributions were determined at varying sampling volumes. Perfusion heterogeneity increased linearly on a log-log plot of coefficient of variation vs. volume, down to the smallest sampling size of 0.53 mm3. The average fractal dimension, a scale-independent measure of perfusion distribution, was 1.2. This value is similar to that of other larger species such as dogs, pigs, and horses. Pulmonary perfusion heterogeneity increases continuously and remains fractal down to the acinar level. Despite the large degree of perfusion heterogeneity at the acinar level, gases are efficiently exchanged.
Continuous intracellular recording from mammalian neurons exposed to hyperbaric helium, oxygen, or air
Authors: Dean Jay B. , Mulkey Daniel K.
Published: December 2017

We developed a hyperbaric chamber for intracellular recording in rat brain stem slices during continuous compression and decompression of the tissue bath with the inert gas helium. Air, rather than helium, was also used as the compression medium in some cases to increase tissue nitrogen levels. An important feature is the chamber door, which opens or closes rapidly at 1 atmosphere absolute (ATA) for increased accessibility of the microelectrode. The door also closes and seals smoothly without disrupting the intracellular recording. Hyperbaric oxygen was administered during helium compression using a separate pressure cylinder filled with perfusate equilibrated with 2.3–3.3 ATA oxygen. Measurements of tissue/bath Po 2 and pH confirmed that the effects of compression using helium or air could be differentiated from those due to increased Po 2. One hundred and thirteen neurons were studied during 375 compression cycles ranging from 1 to 20 ATA (mode 3.0 ATA). We conclude that it is technically feasible to record intracellularly from the same mammalian neuron while changing ambient pressure over a physiologically important range. These techniques will be useful for studying how various hyperbaric environments affect neurophysiological mechanisms.
Invited Review: What do we know about the effects of spaceflight on bone?
Authors: Turner Russell T.
Published: December 2017

This review of the peer-reviewed literature focuses on the effects of spaceflight on bone. Studies performed in humans and laboratory animals have revealed abnormalities in bone and mineral metabolism that suggest that long-duration spaceflight will have detrimental effects on the skeleton. However, because of large gaps in our knowledge, it is not presently possible to estimate the magnitude of the health risk, individual variations in risk, effective countermeasures, or mechanism(s) of action. Specific recommendations are made for future research to ascertain risk and develop appropriate countermeasures.
Adaptation of laser-Doppler flowmetry to measure cerebral blood flow in the fetal sheep
Authors: Lan Jiang , Hunter Christian J. , Murata Tomoaki , Power Gordon G.
Published: December 2017

The purpose of this study was to devise a means to use laser-Doppler flowmetry to measure cerebral perfusion before birth. The method has not been used previously, largely because of intrauterine movement artifacts. To minimize movement artifacts, a probe holder was molded from epoxy putty to the contour of the fetal skull. A curved 18-gauge needle was embedded in the holder. At surgery, the holder, probe, and skull were fixed together with tissue glue. Residual signals were recorded after fetal death and after maternal death 1 h later. These averaged <5% of baseline flow signals, indicating minimal movement artifact. To test the usefulness of the method, cerebral flow responses were measured during moderate fetal hypoxia induced by giving the ewes ∼10% oxygen in nitrogen to breathe. As fetal arterial Po 2 decreased from 21.1 ± 0.5 to 10.7 ± 0.4 Torr during a 30-min period, cerebral perfusion increased progressively to 56 ± 8% above baseline. Perfusion then returned to baseline levels during a 30-min recovery period. These responses are quantitatively similar to those spot observations that have been recorded earlier using labeled microspheres. We conclude that cerebral perfusion can be successfully measured by using laser-Doppler flowmetry with the unanesthetized, chronically prepared fetal sheep as an experimental model. With this method, relative changes of perfusion from a small volume of the ovine fetal brain can be measured on a continuous basis, and movement artifacts can be reduced to 5% of measured flow values.
Gastrointestinal function during exercise: comparison of water, sports drink, and sports drink with caffeine
Authors: Van Nieuwenhoven M. A. , Brummer R.-J. M. , Brouns F.
Published: December 2017

Caffeine is suspected to affect gastrointestinal function. We therefore investigated whether supplementation of a carbohydrate-electrolyte solution (CES) sports drink with 150 mg/l caffeine leads to alterations in gastrointestinal variables compared with a normal CES and water using a standardized rest-exercise-rest protocol. Ten well-trained subjects underwent a rest-cycling-rest protocol three times. Esophageal motility, gastroesophageal reflux, and intragastric pH were measured by use of a transnasal catheter. Orocecal transit time was measured using breath-H2 measurements. A sugar absorption test was applied to determine intestinal permeability and glucose absorption. Gastric emptying was measured via the 13C-acetate breath test. In the postexercise episode, midesophageal pressure was significantly lower in the CES + caffeine trial compared with the water trial ( P = 0.017). There were no significant differences between the three drinks for gastric pH and reflux during the preexercise, the cycling, and the postexercise episode, respectively. Gastric emptying, orocecal transit time, and intestinal permeability showed no significant differences between the three trials. However, glucose absorption was significantly increased in the CES + caffeine trial compared with the CES trial ( P = 0.017). No significant differences in gastroesophageal reflux, gastric pH, or gastrointestinal transit could be observed between the CES, the CES + caffeine, and the water trials. However, intestinal glucose uptake was increased in the CES + caffeine trial.
Ventilatory responses to acute and chronic hypoxia in mice: effects of dopamine D2receptors
Authors: Huey K. A. , Low M. J. , Kelly M. A. , Juarez R. , Szewczak J. M. , Powell F. L.
Published: December 2017

We used genetically engineered D2receptor-deficient [D2-(−/−)] and wild-type [D2-(+/+)] mice to test the hypothesis that dopamine D2receptors modulate the ventilatory response to acute hypoxia [hypoxic ventilatory response (HVR)] and hypercapnia [hypercapnic ventilatory response (HCVR)] and time-dependent changes in ventilation during chronic hypoxia. HVR was independent of gender in D2-(+/+) mice and significantly greater in D2-(−/−) than in D2-(+/+) female mice. HCVR was significantly greater in female D2–(+/+) mice than in male D2-(+/+) and was greater in D2-(−/−) male mice than in D2-(+/+) male mice. Exposure to hypoxia for 2–8 days was studied in male mice only. D2-(+/+) mice showed time-dependent increases in “baseline” ventilation (inspired Po2= 214 Torr) and hypoxic stimulated ventilation (inspired Po2= 70 Torr) after 8 days of acclimatization to hypoxia, but D2-(−/−) mice did not. Hence, dopamine D2receptors modulate the acute HVR and HCVR in mice in a gender-specific manner and contribute to time-dependent changes in ventilation and the acute HVR during acclimatization to hypoxia.
Effects of anodal vs. cathodal pacing on the mechanical performance of the isolated rabbit heart
Authors: Thakral Anshul , Stein Louis H. , Shenai Mahesh , Gramatikov Boris I. , Thakor Nitish V.
Published: December 2017

Previous studies have suggested that anodal pacing enhances electrical conduction in the heart near the pacing site. It was hypothesized that enhanced conduction by anodal pacing would also enhance ventricular pressure in the heart. Left ventricular pressure measurements were made in isolated, Langendorff-perfused rabbit hearts by means of a Millar pressure transducer with the use of a balloon catheter fixed in the left ventricle. The pressure wave was analyzed for maximum pressure (Pmax) generated in the left ventricle and the work done by the left ventricle (Parea). Eight hearts were paced with monophasic square-wave pulses of varying amplitudes (2, 4, 6, and 8 V) with 100 pulses of each waveform delivered to the epicardium. Anodal stimulation pulses showed statistically significant improvement in mechanical response at 2, 4, and 8 V. Relative to unipolar cathodal pacing, unipolar anodal pacing improved Pmax by 4.4 ± 2.3 (SD), 5.3 ± 3.1, 3.5 ± 4.9, and 4.8 ± 1.9% at 2, 4, 6, and 8 V, respectively. Unipolar anodal stimulation also improved Parea by 9.0 ± 3.0, 12.0 ± 6.0, 10.1 ± 7.7, and 11.9 ± 6.0% at 2, 4, 6, and 8 V, respectively. Improvements in Pmax and Parea indicate that an anodally paced heart has a stronger mechanical response than does a cathodally paced heart. Anodal pacing might be useful as a novel therapeutic technology to treat mechanically impaired or failed hearts.
Increases in submaximal cycling efficiency mediated by altitude acclimatization
Authors: Green H. J. , Roy B. , Grant S. , Hughson R. , Burnett M. , Otto C. , Pipe A. , McKenzie D. , Johnson M.
Published: December 2017

To investigate the hypothesis that respiratory gas exchange and, in particular, the O2consumption (V˙o2) response to exercise is altered after a 21-day expedition to 6,194 m, five male climbers (age 28.2 ± 2 yr; weight 76.9 ± 4.3 kg; means ± SE) performed a progressive and prolonged two-step cycle test both before and 3–4 days after return to sea level. During both exercise tests, a depression ( P < 0.05) inV˙o2(l/min) and an increase ( P < 0.05) in minute ventilation (V˙e btps; l/min) and respiratory exchange ratio were observed after the expedition. These changes occurred in the absence of changes in CO2production (l/min). During steady-state submaximal exercise, net efficiency, calculated from the rates of the mechanical power output to the energy expended (V˙o2) above that measured at rest, increased ( P < 0.05) from 25.9 ± 1.6 to 31.3 ± 1.3% at the lighter power output and from 24.4 ± 1.3 to 29.5 ± 1.5% at the heavy power output. These changes were accompanied by a 4.5% reduction ( P< 0.05) in peak V˙o2(3.99 ± 0.17 vs. 3.81 ± 0.18 l/min). After the expedition, an increase ( P < 0.05) in hemoglobin concentration (15.0 ± 0.49 vs. 15.8 ± 0.41 g/100 ml) was found. It is concluded that, because resting V˙o2was unchanged, net efficiency is enhanced during submaximal exercise after a mountaineering expedition when the exercise is performed soon after return to sea level conditions.
Invited Review: Gravitational biology of the neuromotor systems: a perspective to the next era
Authors: Edgerton V. Reggie , Roy Roland R.
Published: December 2017

Earth's gravity has had a significant impact on the designs of the neuromotor systems that have evolved. Early indications are that gravity also plays a key role in the ontogenesis of some of these design features. The purpose of the present review is not to assess and interpret a body of knowledge in the usual sense of a review but to look ahead, given some of the general concepts that have evolved and observations made to date, which can guide our future approach to gravitational biology. We are now approaching an era in gravitational biology during which well-controlled experiments can be conducted for sustained periods in a microgravity environment. Thus it is now possible to study in greater detail the role of gravity in phylogenesis and ontogenesis. Experiments can range from those conducted on the simplest levels of organization of the components that comprise the neuromotor system to those conducted on the whole organism. Generally, the impact of Earth's gravitational environment on living systems becomes more complex as the level of integration of the biological phenomenon of interest increases. Studies of the effects of gravitational vectors on neuromotor systems have and should continue to provide unique insight into these mechanisms that control and maintain neural control systems designed to function in Earth's gravitational environment. A number of examples are given of how a gravitational biology perspective can lead to a clearer understanding of neuromotor disorders. Furthermore, the technologies developed for spaceflight studies have contributed and should continue to contribute to studies of motor dysfunctions, such as spinal cord injury and stroke. Disorders associated with energy support and delivery systems and how these functions are altered by sedentary life styles at 1 G and by space travel in a microgravity environment are also discussed.
Effects of fatigue on sarcoplasmic reticulum and myofibrillar properties of rat single muscle fibers
Authors: Danieli-Betto D. , Germinario E. , Esposito A. , Biral D. , Betto R.
Published: December 2017

Force decline during fatigue in skeletal muscle is attributed mainly to progressive alterations of the intracellular milieu. Metabolite changes and the decline in free myoplasmic calcium influence the activation and contractile processes. This study was aimed at evaluating whether fatigue also causes persistent modifications of key myofibrillar and sarcoplasmic reticulum (SR) proteins that contribute to tension reduction. The presence of such modifications was investigated in chemically skinned fibers, a procedure that replaces the fatigued cytoplasm from the muscle fiber with a normal medium. Myofibrillar Ca2+sensitivity was reduced in slow-twitch muscle (for example, the pCa value corresponding to 50% of maximum tension was 6.23 ± 0.03 vs. 5.99 + 0.05, P < 0.01, in rested and fatigued fibers) and not modified in fast-twitch muscle. Phosphorylation of the regulatory myosin light chain isoform increased in fast-twitch muscle. The rate of SR Ca2+uptake was increased in slow-twitch muscle fibers (14.2 ± 1.0 vs. 19.6 ± 2.5 nmol · min−1· mg fiber protein−1, P < 0.05) and not altered in fast-twitch fibers. No persistent modifications of SR Ca2+release properties were found. These results indicate that persistent modifications of myofibrillar and SR properties contribute to fatigue-induced muscle force decline only in slow fibers. These alterations may be either enhanced or counteracted, in vivo, by the metabolic changes that normally occur during fatigue development.
Respiratory neuronal activity during apnea and poststimulatory effects of laryngeal origin in the cat
Authors: Bongianni Fulvia , Mutolo Donatella , Carfì Marco , Fontana Giovanni A. , Pantaleo Tito
Published: December 2017

We investigated the behavior of medullary respiratory neurons in cats under pentobarbitone anesthesia, vagotomized, paralysed, and artificially ventilated to elucidate neural mechanisms underlying apnea and poststimulatory respiratory depression induced by superior laryngeal nerve (SLN) stimulation. Inspiratory neurons were completely inhibited during SLN stimulation and poststimulatory apnea. During recovery of inspiratory activity, augmenting inspiratory neurons were depressed, decrementing inspiratory neurons were excited, and late inspiratory neurons displayed unchanged bursts closely locked to the end of the inspiratory phase. Augmenting expiratory neurons were either silenced or displayed different levels of tonic activity during SLN stimulation; some of them were clearly activated. These expiratory neurons displayed activity during poststimulatory apnea, before the onset of the first recovery phrenic burst. Postinspiratory or decrementing expiratory neurons were activated during SLN stimulation; their discharge continued with a decreasing trend during poststimulatory apnea. The results support the three-phase theory of rhythm generation and the view that SLN stimulation provokes a postinspiratory apnea that could represent the inhibitory component of respiratory reflexes of laryngeal origin, such as swallowing. In addition, because a subpopulation of augmenting expiratory neurons displays activation during SLN stimulation, the hypothesis can be advanced that not only postinspiratory, or decrementing expiratory neurons, but also augmenting expiratory neurons may be involved in the genesis of apnea and poststimulatory phenomena. Finally, the increase in the activity of decrementing inspiratory neurons after the end of SLN stimulation may contribute to the generation of poststimulatory respiratory depression by providing an inhibitory input to bulbospinal augmenting inspiratory neurons.
Blood pressure and heart rate during periodic breathing while asleep at high altitude
Authors: Insalaco Giuseppe , Romano Salvatore , Salvaggio Adriana , Braghiroli Alberto , Lanfranchi Paola , Patruno Vincenzo , Marrone Oreste , Bonsignore Maria R. , Donner Claudio F. , Bonsignore Giovanni
Published: December 2017

The ventilatory and arterial blood pressure (ABP) responses to isocapnic hypoxia during wakefulness progressively increased in normal subjects staying 4 wk at 5,050 m (Insalaco G, Romano S, Salvaggio A, Braghiroli A, Lanfranchi P, Patruno V, Donner CF, and Bonsignore G; J Appl Physiol 80: 1724–1730, 1996). In the same subjects ( n = 5, age 28–34 yr) and expedition, nocturnal polysomnography with ABP and heart rate (HR) recordings were obtained during the 1st and 4th week to study the cardiovascular effects of phasic (i.e., periodic breathing-dependent) vs. tonic (i.e., acclimatization-dependent) hypoxia during sleep. Both ABP and HR fluctuated during non-rapid eye movement sleep periodic breathing. None of the subjects exhibited an ABP increase during the ventilatory phases that correlated with the lowest arterial oxygen saturation of the preceding pauses. Despite attenuation of hypoxemia, ABP and HR behaviors during sleep in the 4th wk were similar to those in the 1st wk. Because ABP during periodic breathing in the ventilatory phase increased similarly to the ABP response to progressive hypoxia during wakefulness, ABP variations during ventilatory phases may reflect ABP responsiveness to peripheral chemoreflex sensitivity rather than the absolute value of hypoxemia, suggesting a major tonic effect of hypoxia on cardiorespiratory control at high altitude.
Resistance training increases total energy expenditure and free-living physical activity in older adults
Authors: Hunter Gary R. , Wetzstein Carla J. , Fields David A. , Brown Amanda , Bamman Marcas M.
Published: December 2017

The purpose of this study was to determine what effects 26 wk of resistance training have on resting energy expenditure (REE), total free-living energy expenditure (TEE), activity-related energy expenditure (AEE), engagement in free-living physical activity as measured by the activity-related time equivalent (ARTE) index, and respiratory exchange ratio (RER) in 61- to 77-yr-old men ( n = 8) and women ( n = 7). Before and after training, body composition (four-compartment model), strength, REE, TEE (doubly labeled water), AEE (TEE − REE + thermic response to meals), and ARTE (AEE adjusted for energy cost of standard activities) were evaluated. Strength (36%) and fat-free mass (2 kg) significantly increased, but body weight did not change. REE increased 6.8%, whereas resting RER decreased from 0.86 to 0.83. TEE (12%) and ARTE (38%) increased significantly, and AEE (30%) approached significance ( P = 0.06). The TEE increase remained significant even after adjustment for the energy expenditure of the resistance training. In response to resistance training, TEE increased and RER decreased. The increase in TEE occurred as a result of increases in both REE and physical activity. These results suggest that resistance training may have value in increasing energy expenditure and lipid oxidation rates in older adults, thereby improving their metabolic profiles.
Venoarterial CO2 difference during regional ischemic or hypoxic hypoxia
Authors: Vallet Benoit , Teboul Jean-Louis , Cain Stephen , Curtis Scott
Published: December 2017

To test the role of blood flow in tissue hypoxia-related increased veno-arterial Pco 2difference (ΔPco 2), we decreased O2 delivery (D˙o 2) by either decreasing flow [ischemic hypoxia (IH)] or arterial Po 2 [hypoxic hypoxia (HH)] in an in situ, vascularly isolated, innervated dog hindlimb perfused with a pump-membrane oxygenator system. Twelve anesthetized and ventilated dogs were studied, with systemic hemodynamics maintained within normal range. In the IH group ( n = 6), hindlimbD˙o 2 was progressively lowered every 15 min by decreasing pump-controlled flow from 60 to 10 ml · kg−1 · min−1, with arterial Po 2 constant at 100 Torr. In the HH group ( n = 6), hindlimbD˙o 2 was progressively lowered every 15 min by decreasing Po 2 from 100 to 15 Torr, when flow was constant at 60 ml · kg−1 · min−1. LimbD˙o 2, O2 uptake (V˙o 2), and ΔPco 2 were obtained every 15 min. Below the criticalD˙o 2,V˙o 2 decreased, indicating dysoxia, and O2 extraction ratio (V˙o 2/D˙o 2) rose continuously and similarly in both groups, reaching a maximal value of ∼90%. ΔPco 2 significantly increased in IH but never differed from baseline in HH. We conclude that absence of increased ΔPco 2 does not preclude the presence of tissue dysoxia and that decreased flow is a major determinant in increased ΔPco 2.
Diaspirin cross-linked hemoglobin improves oxygen extraction capabilities in endotoxic shock
Authors: Creteur Jacques , Zhang Haibo , De Backer Daniel , Sun Qinghua , Vincent Jean-Louis
Published: December 2017

We studied the effects of diaspirin cross-linked hemoglobin (DCLHb), a cell-free hemoglobin derived from human erythrocytes, on blood flow distribution and tissue oxygen extraction capabilities in endotoxic shock. Eighteen pentobarbital sodium-anesthetized, mechanically ventilated dogs received 2 mg/kg of E. coli endotoxin, followed by saline resuscitation to restore cardiac filling pressures to baseline levels. The animals were randomly divided into three groups: six served as control, six received DCLHb at a dose of 500 mg/kg ( group 1) and six DCLHb at a dose of 1,000 mg/kg ( group 2). Cardiac tamponade was then induced by saline injection in the pericardial sac to progressively reduce cardiac index and thereby allow study of tissue oxygen extraction capabilities. DCLHb had a dose-dependent vasopressor effect but did not significantly alter cardiac index or regional blood flow. During cardiac tamponade, critical oxygen delivery was 12.8 ± 0.7 ml · kg−1· min−1in the control group, but 8.6 ± 0.9 and 8.2 ± 0.7 ml · kg−1· min−1in groups 1 and 2, respectively (both P < 0.05 vs. control group). The critical oxygen extraction ratio was 39.1 ± 3.1% in the control group but 58.7 ± 12.8% and 60.2 ± 9.0% in groups 1and 2, respectively. We conclude that DCLHb can improve whole body oxygen extraction capabilities during endotoxic shock in dogs.
Unilateral lung edema: effects on pulmonary gas exchange, hemodynamics, and pulmonary perfusion distribution
Authors: Slama Klaus , Gesch Mareike , Böck Johannes C. , Pietschmann Sylvia M. , Schaffartzik Walter , Pison Ulrich
Published: December 2017

Two types of unilateral lung edema in sheep were characterized regarding their effects on pulmonary gas exchange, hemodynamics, and distribution of pulmonary perfusion. One edema type was induced with aerosolized HCl (0.15 M, pH 1.0) and the other with NaCl (0.15 M, pH 7.4). Both aerosols were nebulized continuously for 4 h into left lungs. In HCl-treated animals, pulmonary gas exchange deteriorated [from a partial arterial O2 pressure-to-inspired O2 fraction ratio (PaO2 /Fi O2 ) of 254 at baseline to 187 after 4 h HCl]. In addition, pulmonary artery pressure and total pulmonary vascular resistance increased (from 16 to 19 mmHg and from 133 to 154 dyn · s · cm−5, respectively). In NaCl-treated animals, only the central venous pressure significantly increased (from 7 to 9 mmHg). Distribution of pulmonary perfusion (measured with fluorescent microspheres) changed differently in both groups. After HCl application, 6% more blood flow was directed to the treated lung, whereas, after NaCl, 5% more blood flow was directed to the untreated lung. HCl and NaCl treatment both induce an equivalent lung edema, but only HCl treatment is associated with gas exchange alteration and tissue damage. Redistribution of pulmonary perfusion maintains gas exchange during NaCl treatment and decreases it during HCl inhalation.
5-Hydroxytryptophan-induced respiratory recovery after cervical spinal cord hemisection in rats
Authors: Zhou Shi-Yi , Goshgarian Harry G.
Published: December 2017

The present study investigates the role of serotonin in respiratory recovery after spinal cord injury. Experiments were conducted on C2 spinal cord hemisected, anesthetized, vagotomized, paralyzed, and artificially ventilated rats in which end-tidal CO2 was monitored and maintained. Before drug administration, the phrenic nerve ipsilateral to hemisection showed no respiratory-related activity due to the disruption of the descending bulbospinal respiratory pathways by spinal cord hemisection. 5-Hydroxytryptophan (5-HTP), a serotonin precursor, was administrated intravenously. 5-HTP induced time- and dose-dependent increases in respiratory recovery in the phrenic nerve ipsilateral to hemisection. Although the 5-HTP-induced recovery was initially accompanied by an increase in activity in the contralateral phrenic nerve, suggesting an increase in descending respiratory drive, the recovery persisted well after activity in the contralateral nerve returned to predrug levels. 5-HTP-induced effects were reversed by a serotonin receptor antagonist, methysergide. Because experiments were conducted on animals subjected to C2 spinal cord hemisection, the recovery was most likely mediated by the activation of a latent respiratory pathway spared by the spinal cord injury. The results suggest that serotonin is an important neuromodulator in the unmasking of the latent respiratory pathway after spinal cord injury. In addition, the results also suggest that the maintenance of 5-HTP-induced respiratory recovery may not require a continuous enhancement of central respiratory drive.
Mechanical properties of cultured human airway smooth muscle cells from 0.05 to 0.4 Hz
Authors: Maksym Geoffrey N. , Fabry Ben , Butler James P. , Navajas Daniel , Tschumperlin Daniel J. , Laporte Johanne D. , Fredberg Jeffrey J.
Published: December 2017

We investigated the rheological properties of living human airway smooth muscle cells in culture and monitored the changes in rheological properties induced by exogenous stimuli. We oscillated small magnetic microbeads bound specifically to integrin receptors and computed the storage modulus (G′) and loss modulus (G") from the applied torque and the resulting rotational motion of the beads as determined from their remanent magnetic field. Under baseline conditions, G′ increased weakly with frequency, whereas G" was independent of the frequency. The cell was predominantly elastic, with the ratio of G" to G′ (defined as η) being ∼0.35 at all frequencies. G′ and G" increased together after contractile activation and decreased together after deactivation, whereas η remained unaltered in each case. Thus elastic and dissipative stresses were coupled during changes in contractile activation. G′ and G" decreased with disruption of the actin fibers by cytochalasin D, but η increased. These results imply that the mechanisms for frictional energy loss and elastic energy storage in the living cell are coupled and reside within the cytoskeleton.
Continuous enteral nutrition attenuates pulmonary edema in rats exposed to 100% oxygen
Authors: Factor Phillip , Ridge Karen , Alverdy John , Sznajder Jacob I.
Published: December 2017

Adult rats exposed to hyperoxia develop anorexia, weight loss, and a lung injury characterized by pulmonary edema and decreased lung liquid clearance. We hypothesized that maintenance of nutrition during hyperoxia could attenuate hyperoxia-induced pulmonary edema. To test this hypothesis, we enterally fed adult male Sprague-Dawley rats via gastrostomy tubes and exposed them to oxygen (inspired O2 fraction >0.95) for 64 h. In contrast to controls, enterally fed hyperoxic animals did not lose weight and had smaller pleural effusions and wet-to-dry weight ratios (a measure of lung edema) that were not different from room air controls. Enterally fed rats exposed to hyperoxia had increased levels of mRNA for the Na+-K+-ATPase α1- and β1-subunits and glutathione peroxidase. These findings suggest that maintenance of nutrition during an oxidative lung injury reduces lung edema, perhaps by allowing for continued expression and function of protective proteins such as the Na+-K+-ATPase.
Simplified rat intubation using a new oropharyngeal intubation wedge
Authors: Jou I-Ming , Tsai Ya-Ting , Tsai Ching-Lin , Wu Ming-Ho , Chang Han-Yu , Wang Nai-San
Published: December 2017

Our new oropharyngeal intubation wedge made from a plastic 3-ml syringe has been used successfully for the expansion of the oropharyngeal cavity and visualization of vocal cords for endotracheal intubation in the rat. All the animals we used tolerated the intubation and ventilation procedures in a series of experiments. After the proper setting of the respirator, vital signs were maintained within normal range. The postmortem examination and measurements in the upper airway confirmed that the endotracheal tube was properly sited and also demonstrated the precise size of the device that should be used. The main advantages of this method include low cost, simplicity, and reliability. Furthermore, because no expensive, elaborate, difficult-to-operate, or hard-to-get special equipment is needed, this technique can be used in every laboratory.
Initial ventilatory and circulatory responses to dynamic exercise are slowed in the elderly
Authors: Ishida Koji , Sato Yasutake , Katayama Keisho , Miyamura Miharu
Published: December 2017

To elucidate the characteristics of ventilatory and circulatory responses at the onset of brief and light exercise in the elderly, 13 healthy, elderly men, aged 66.8 yr (mean), exerted bilateral leg extension-flexion movements for only 20 s with a weight around each ankle, with each weight being ∼2.5% of their body mass. Similar movements were passively performed on the subjects by the experimenters. These results were compared with those of 13 healthy, young men (22.9 yr). Minute ventilation increased at the onset of voluntary exercise and passive movements in both groups but showed a slower increase in the elderly. Heart rate also increased in both groups but showed less change in the elderly. Mean blood pressure temporarily decreased in both groups but less in the elderly. The magnitude of relative change (gain) of heart rate in the elderly was significantly smaller than that in the young, whereas the increasing rate to reach one-half of the gain (response time) of ventilation in the elderly was significantly slower than that in the young. Similar tendencies were observed in the passive movements. It is concluded that the elderly show slower ventilatory response and attenuated circulatory response at the onset of dynamic voluntary exercise and passive movements.
Effect of gravity on aerosol dispersion and deposition in the human lung after periods of breath holding
Authors: Darquenne Chantal , Paiva Manuel , Prisk G. Kim
Published: December 2017

To determine the extent of the role that gravity plays in dispersion and deposition during breath holds, we performed aerosol bolus inhalations of 1-μm-diameter particles followed by breath holds of various lengths on four subjects on the ground (1G) and during short periods of microgravity (μG). Boluses of ∼70 ml were inhaled to penetration volumes (Vp) of 150 and 500 ml, at a constant flow rate of ∼0.45 l/s. Aerosol concentration and flow rate were continuously measured at the mouth. Aerosol deposition and dispersion were calculated from these data. Deposition was independent of breath-hold time at both Vp in μG, whereas, in 1G, deposition increased with increasing breath hold time. At Vp = 150 ml, dispersion was similar at both gravity levels and increased with breath hold time. At Vp = 500 ml, dispersion in 1G was always significantly higher than in μG. The data provide direct evidence that gravitational sedimentation is the main mechanism of deposition and dispersion during breath holds. The data also suggest that cardiogenic mixing and turbulent mixing contribute to deposition and dispersion at shallow Vp.
Inhaled budesonide inhibits OVA-induced airway narrowing, inflammation, and cys-LT synthesis in BN rats
Authors: Xu Lijing , Olivenstein Ronald , Martin James G. , Powell William S.
Published: December 2017

The objective of the present investigation was to examine the effects of an inhaled glucocorticoid, budesonide, on antigen-induced production of cysteinyl leukotrienes (cys-LTs) and pulmonary inflammatory cell infiltration in the Brown Norway rat, an animal model of asthma. Two weeks after sensitization to ovalbumin, rats were treated with budesonide (2.5 mg/kg) 18 and 1 h before challenge with antigen. Budesonide abolished the late response to ovalbumin ( P < 0.02) and strongly inhibited the in vivo synthesis of N-acetyl-leukotriene E4, an indicator of cys-LT synthesis, during this period ( P < 0.005). Both total bronchoalveolar lavage (BAL) cells ( P < 0.01) and BAL macrophages ( P < 0.005) were markedly reduced to ∼25% of their control levels after treatment with budesonide. It can be concluded that inhibition of the antigen-induced late response in Brown Norway rats by budesonide is associated with reductions in both BAL macrophages and cys-LT synthesis. It is possible that the effect of budesonide on cys-LT synthesis is related to its effects on pulmonary macrophages.
Effects of phrenicotomy and exercise on hypoxia-induced changes in phrenic motor output
Authors: Bach Karen B. , Mitchell Gordon S.
Published: December 2017

To investigate models of plasticity in respiratory motor output, we determined the effects of chronic unilateral phrenicotomy and/or exercise on time-dependent responses to episodic hypoxia in the contralateral phrenic nerve. Anesthetized (urethane), ventilated, and vagotomized rats were presented with three, 5-min episodes of isocapnic hypoxia (11% O2), separated by 5 min of hyperoxia (50% O2). Integrated phrenic (and hypoglossal) nerve discharge were recorded before and during each hypoxic episode, for the first 5 min after the first hypoxic episode, and at 30 and 60 min after the final episode. Of 36 rats, one-half were sedentary while the other one-half had free access to a running wheel; each of these groups was split into three subgroups: 1) unoperated, 2) chronic left phrenicotomy (27–37 days), and 3) sham operated. Neither unilateral phrenicotomy nor running wheel activity influenced the short-term hypoxic phrenic response (during hypoxia) or long-term facilitation (posthypoxia). Posthypoxia frequency decline was exaggerated in phrenicotomized-sedentary rats relative to unoperated-sedentary rats (change in burst frequency = −23 ± 4 vs. −11 ± 5 bursts/min, respectively; 5 min posthypoxia; P < 0.05), an effect that was eliminated by spontaneous exercise. The results indicate that neither voluntary running nor unilateral phrenicotomy has major effects on time-dependent hypoxic phrenic responses, with the exception of an unexpected effect of phrenicotomy on posthypoxia frequency decline in sedentary rats.
Downhill running preferentially increases CGRP in fast glycolytic muscle fibers
Authors: Homonko Darlene A. , Theriault Elizabeth
Published: December 2017

Calcitonin gene-related peptide (CGRP) is present in some spinal cord motoneurons and at neuromuscular junctions in skeletal muscle. We previously reported increased numbers of CGRP-positive (CGRP+) motoneurons supplying hindlimb extensors after downhill exercise (Homonko DA and Theriault E, Inter J Sport Med 18: 1–7, 1997). The present study identifies the responding population with respect to muscle and motoneuron pool and correlates changes in CGRP with muscle fiber type-identified end plates. Twenty seven rats were divided into the following groups: control and 72 h and 2 wk postexercise. FluoroGold was injected into the soleus, lateral gastrocnemius, and the proximal (mixed fiber type) or distal (fast-twitch glycolytic) regions of the medial gastrocnemius (MG). Untrained animals ran downhill on a treadmill for 30 min. The number of FluoroGold/CGRP+ motoneurons within proximal and distal MG increased by 72 h postexercise ( P < 0.05). No significant changes were observed in soleus or lateral gastrocnemius motoneurons postexercise. The number of α-bungarotoxin/CGRP+ motor end plates in the MG increased exclusively at fast-twitch glycolytic muscle fibers 72 h and 2 wk postexercise ( P < 0.05). One interpretation of these results is that unaccustomed exercise preferentially activates fast-twitch glycolytic muscle fibers in the MG.
Aminophylline modulation of the mouse respiratory network changes during postnatal maturation
Authors: Wilken B. , Ramirez J. M. , Hanefeld F. , Richter D. W.
Published: December 2017

Aminophylline is a respiratory stimulant commonly used for the treatment of central apnea. Experiences from clinical practice, however, revealed that aminophylline is not reliably effective in preterm infants, whereas it is normally effective in infants and mature patients. In an established animal model for postnatal development of respiratory control mechanisms, we therefore examined the hypothesis that the clinical observations reflect a developmental change in the sensitivity of the central respiratory network to methylxanthines. The medullary respiratory network was isolated at different postnatal ages ( postnatal days 1–13; P1–P13) in a transverse mouse brain stem slice preparation. This preparation contains the pre-Bötzinger complex (PBC), a region that is critical for generation of respiratory rhythm. Spontaneous rhythmic respiratory activity was recorded from the hypoglossal (XII) rootlets and from neurons in the PBC by using the whole cell patch clamp technique. Bath-applied aminophylline [20 μM] increased the frequency (+41%) in neonatal animals (P1–P6) without affecting the amplitude of respiratory burst activity in XII rootlets. The same concentration of aminophylline did not have any significant effect on the frequency of respiratory XII bursts but increased the amplitude (+31%) in juvenile animals (P7–P13). In the same age group, aminophylline also augmented the amplitude and the duration of respiratory synaptic drive currents in respiratory PBC neurons. The data demonstrate that augmentation of the respiratory output is due to direct enhancement of central respiratory network activity and increase of synaptic drive of hypoglossal motoneurons in juvenile, but not neonatal, animals. This indicates a developmental change in the efficacy of aminophylline to reinforce central respiratory network activity. Therefore, we believe that the variable success in treating respiratory disturbances in premature infants reflects maturational changes in the expression of receptors and/or intracellular signal pathways in the central respiratory network.
Postprandial lipemia in young men and women of contrasting training status
Authors: Herd Sara L. , Lawrence Janet E. M. , Malkova Dale , Murphy Marie H. , Mastana Sarabjit , Hardman Adrianne E.
Published: December 2017

This study compared the postprandial triacylglycerol (TAG) response to a high-fat meal in trained and untrained normolipidemic young adults after 2 days' abstinence from exercise. Fifty-three subjects (11 endurance-trained men, 9 endurance-trained women, 10 sprint/strength-trained men, 11 untrained men, 11 untrained women) consumed a meal (1.2 g fat, 1.1 g carbohydrate, 66 kJ per kg body mass) after a 12-h fast. Venous blood samples were obtained in the fasted state and at intervals until 6 h. Postprandial responses were the areas under the plasma or serum concentration-vs.-time curves. Neither fasting TAG concentrations nor the postprandial TAG response differed between trained and untrained subjects. The insulinemic response was 29% lower in endurance-trained men than in untrained men [mean difference −37.4 (95% confidence interval −62.9 to −22.9) μIU/ml × h, P = 0.01]. Responses of plasma glucose, serum insulin, and plasma nonesterified fatty acids were all lower for endurance-trained men than for untrained men. These findings suggest that, in young adults, no effect of training on postprandial lipemia can be detected after 60 h without exercise. The effect on postprandial insulinemia may persist for longer.
Invited Review: Mechanochemical signal transduction in the fetal lung
Authors: Liu Mingyao , Post Martin
Published: December 2017

Growth and maturation of fetal lungs are regulated by both humoral and physical factors. Mechanical stretch stimulates fetal lung cell proliferation and affects fetal lung maturation by influencing the production of extracellular matrix molecules and the expression of specific genes of fetal lung cells. These effects are mediated through special signal transduction pathways in fetal lung cells. Various in vivo and in vitro model systems have been developed to investigate the mechanotransduction process. The diversity and discrepancy of these studies have raised many questions. We will briefly summarize mechanical force-induced signals in fetal lung cell proliferation and differentiation and then discuss several important issues related to these studies.