bluuebunny/crossref_metadata_2025 huggingface dataset:
Carbonic anhydrase inhibition delays plasma lactate appearance with no effect on ventilatory threshold
Authors: Scheuermann Barry W. , Kowalchuk John M. , Paterson Donald H. , Cunningham David A.
Published: December 2017

The effect of carbonic anhydrase (CA) inhibition with acetazolamide (Acz, 10 mg/kg body wt iv) on exercise performance and the ventilatory (V˙eT) and lactate (LaT) thresholds was studied in seven men during ramp exercise (25 W/min) to exhaustion. Breath-by-breath measurements of gas exchange were obtained. Arterialized venous blood was sampled from a dorsal hand vein and analyzed for plasma pH,[Formula: see text], and lactate concentration ([La−]pl).V˙eT [expressed as O2 uptake (V˙o 2), ml/min] was determined using the V-slope method. LaT (expressed asV˙o 2, ml/min) was determined from the work rate (WR) at which [La−]plincreased 1.0 mM above rest levels. Peak WR was higher in control (Con) than in Acz sutdies [339 ± 14 vs. 315 ± 14 (SE) W]. Submaximal exercise V˙o 2 was similar in Acz and Con; the lowerV˙o 2 at exhaustion in Acz than in Con (3.824 ± 0.150 vs. 4.283 ± 0.148 l/min) was appropriate for the lower WR. CO2output (V˙co 2) was lower in Acz than in Con at exercise intensities ≥125 W and at exhaustion (4.375 ± 0.158 vs. 5.235 ± 0.148 l/min). [La−]plwas lower in Acz than in Con during submaximal exercise ≥150 W and at exhaustion (7.5 ± 1.1 vs. 11.5 ± 1.1 mmol/l).V˙eT was similar in Acz and Con (2.483 ± 0.086 and 2.362 ± 0.110 l/min, respectively), whereas the LaT occurred at a higherV˙o 2 in Acz than in Con (2.738 ± 0.223 vs. 2.190 ± 0.235 l/min). CA inhibition with Acz is associated with impaired elimination of CO2 during the non-steady-state condition of ramp exercise. The similarity inV˙eT in Con and Acz suggests that La−production is similar between conditions but La− appearance in plasma is reduced and/or La− uptake by other tissues is enhanced after the Acz treatment.
Water and carbohydrate ingestion during prolonged exercise increase maximal neuromuscular power
Authors: Fritzsche Ricardo G. , Switzer Thomas W. , Hodgkinson Bradley J. , Lee Suk-Ho , Martin James C. , Coyle Edward F.
Published: December 2017

This study investigated the individual and combined effects of water and carbohydrate ingestion during prolonged cycling on maximal neuromuscular power (Pmax), thermoregulation, cardiovascular function, and metabolism. Eight endurance-trained cyclists exercised for 122 min at 62% maximal oxygen uptake in a 35°C environment (50% relative humidity, 2 m/s fan speed). Pmax was measured in triplicate during 6-min periods beginning at 26, 56, 86, and 116 min. On four different occasions, immediately before and during exercise, subjects ingested 1) 3.28 ± 0.21 liters of water with no carbohydrate (W); 2) 3.39 ± 0.23 liters of a solution containing 204 ± 14 g of carbohydrate (W+C); 3) 204 ± 14 g of carbohydrate in only 0.49 ± 0.03 liter of solution (C); and 4) 0.37 ± 0.02 liter of water with no carbohydrate (placebo; Pl). These treatments were randomized, disguised, and presented double blind. At 26 min of exercise, Pmax was similar in all trials. From 26 to 116 min, Pmax declined 15.2 ± 3.3 and 14.5 ± 2.1% during C and Pl, respectively; 10.4 ± 1.9% during W (W > C, W > Pl; P< 0.05); and 7.4 ± 2.2% during W+C (W+C > W, W+C > C, and W+C > Pl; P < 0.05). As an interesting secondary findings, we also observed that carbohydrate ingestion increased heat production, final core temperature, and whole body sweating rate. We conclude that, during prolonged moderate-intensity exercise in a warm environment, ingestion of W attenuates the decline in Pmax. Furthermore, ingestion of W+C attenuates the decline in maximal power more than does W alone, and ingestion of C alone does not attenuate the decline in Pmax compared with Pl.
Effects of exercise on GLUT-4 and glycogenin gene expression in human skeletal muscle
Authors: Kraniou Yorgos , Cameron-Smith David , Misso Marie , Collier Greg , Hargreaves Mark
Published: December 2017

To investigate the effect of exercise on GLUT-4, hexokinase, and glycogenin gene expression in human skeletal muscle, 10 untrained subjects (6 women and 4 men, 21.4 ± 1.2 yr, 66.3 ± 5.0 kg, peak oxygen consumption = 2.30 ± 0.19 l/min) exercised for 60 min on a cycle ergometer at a power output requiring 73 ± 4% peak oxygen consumption. Muscle samples were obtained by needle biopsy before, immediately after, and 3 h after exercise. Gene expression was quantified, relative to 29S ribosomal protein cDNA, by RT-PCR. GLUT-4 gene expression was increased immediately after exercise (1.7 ± 0.4 vs. 0.9 ± 0.3 arbitrary units; P < 0.05) and remained significantly higher than baseline 3 h after the end of exercise (2.2 ± 0.4 vs. 0.9 ± 0.3 arbitrary units; P < 0.05). Hexokinase II gene expression was significantly higher than the resting value 3 h after the end of exercise (2.9 ± 0.4 vs. 1.3 ± 0.3 arbitrary units; P < 0.05). Exercise increased glycogenin mRNA more than twofold (2.8 ± 0.6 vs. 1.2 ± 0.2 arbitrary units; P < 0.05) 3 h after the end of exercise. For the first time, we report that a single bout of exercise is sufficient to cause upregulation of GLUT-4 and glycogenin gene expression in human skeletal muscle. Whether these increases, together with the associated increase in hexokinase II gene expression, lead to increased expression of these key proteins in skeletal muscle and contribute to the enhanced skeletal muscle glucose uptake, glycogen synthesis, and insulin action observed following exercise remains to be determined.
Alveolar environment influences the metabolic and biophysical properties of exogenous surfactants
Authors: Puligandla Pramod S. , Gill Tara , McCaig Lynda A. , Yao Li-Juan , Veldhuizen Ruud A. W. , Possmayer Fred , Lewis James F.
Published: December 2017

Several factors have been shown to influence the efficacy of exogenous surfactant therapy in the acute respiratory distress syndrome. We investigated the effects of four different alveolar environments (control, saline-lavaged, N-nitroso- N-methylurethane, and hydrochloric acid) on the metabolic and functional properties of two exogenous surfactant preparations: bovine lipid extract surfactant and recombinant surfactant-associated protein (SP) C drug product (rSPC) administered to each of these groups. The main difference between these preparations was the lack of SP-B in the rSPC. Our results demonstrated differences in the large aggregate pool sizes recovered from each of the experimental groups. We also observed differences in SP-A content, surface area cycling characteristics, and biophysical activities of these large aggregate forms after the administration of the two exogenous surfactant preparations. We conclude that the alveolar environment plays a critical role, influencing the overall efficacy of exogenous surfactant therapy. Thus further preclinical studies are warranted to investigate the specific factors within the alveolar environment that lead to the differences observed in this study.
Lung function and ventilation inhomogeneity in rat lungs after allergen challenge
Authors: Sánchez-Cifuentes M. Victoria , Rubio Maria L. , Ortega Mercedes , Peces-Barba German , Paiva Manuel , Verbanck Sylvia , Mangado Nicolás González
Published: December 2017

We studied the early response to ovalbumin challenge in sensitized Brown-Norway rats through its effect on N2, He, and SF6 phase III slopes of the single-breath washout and on indexes of lung function. Sensitized rats showed varying degrees of response in terms of pulmonary pressure (Pl), with increases ranging between 125 and 225% of baseline. The sensitized rats presented decreased quasistatic compliance, forced vital capacity, and end-expiratory flow, with all three lung function indexes showing a significant negative correlation with corresponding Pl values. They also showed significant positive correlations of Pl with the N2, He, and SF6 phase III slopes, reflecting diffusion-convection-dependent inhomogeneities generated by conformation changes throughout the entire rat lung. In addition, the rats showing the most marked Pl increases (>150% baseline Pl) also revealed a reversal of the SF6-He slope difference because of a more marked SF6 than He slope increase. This latter finding suggests that the degree of structural heterogeneity during early response is even more marked in the most peripheral rat lung generations.
Altered gravity downregulates aquaporin-1 protein expression in choroid plexus
Authors: Masseguin Christophe , Corcoran Merylee , Carcenac Carole , Daunton Nancy G. , Güell Antonio , Verkman Alan S. , Gabrion Jacqueline
Published: December 2017

Aquaporin-1 (AQP1) is a water channel expressed abundantly at the apical pole of choroidal epithelial cells. The protein expression was quantified by immunocytochemistry and confocal microscopy in adult rats adapted to altered gravity. AQP1 expression was decreased by 64% at the apical pole of choroidal cells in rats dissected 5.5–8 h after a 14-day spaceflight. AQP1 was significantly overexpressed in rats readapted for 2 days to Earth's gravity after an 11-day flight (48% overshoot, when compared with the value measured in control rats). In a ground-based model that simulates some effects of weightlessness and alters choroidal structures and functions, apical AQP1 expression was reduced by 44% in choroid plexus from rats suspended head down for 14 days and by 69% in rats suspended for 28 days. Apical AQP1 was rapidly enhanced in choroid plexus of rats dissected 6 h after a 14-day suspension (57% overshoot, in comparison with control rats) and restored to the control level when rats were dissected 2 days after the end of a 14-day suspension. Decreases in the apical expression of choroidal AQP1 were also noted in rats adapted to hypergravity in the NASA 24-ft centrifuge: AQP1 expression was reduced by 47% and 85% in rats adapted for 14 days to 2 G and 3 G, respectively. AQP1 is downregulated in the apical membrane of choroidal cells in response to altered gravity and is rapidly restored after readaptation to normal gravity. This suggests that water transport, which is partly involved in the choroidal production of cerebrospinal fluid, might be decreased during spaceflight and after chronic hypergravity.
Lung resistance and elastance in spontaneously breathing preterm infants: effects of breathing pattern and demographics
Authors: Pandit Paresh B. , Pyon Kee H. , Courtney Sherry E. , England Sandra E. , Habib Robert H.
Published: December 2017

Reported values of lung resistance (Rl) and elastance (El) in spontaneously breathing preterm neonates vary widely. We hypothesized that this variability in lung properties can be largely explained by both inter- and intrasubject variability in breathing pattern and demographics. Thirty-three neonates receiving nasal continuous positive airway pressure [weight 606–1,792 g, gestational age (GA) of 25–33 wk, 2–49 days old] were studied. Transpulmonary pressure was measured by esophageal manometry and airway flow by face mask pneumotachography. Breath-to-breath changes in Rl and El in each infant were estimated by Fourier analysis of impedance (Z) and by multiple linear regression (MLR). RlMLR(RlMLR= 0.85 × RlZ−0.43; r2= 0.95) and ElMLR(ElMLR= 0.97 × ElZ+ 8.4; r2= 0.98) were highly correlated to RlZand ElZ, respectively. Both Rl(mean ± SD; RlZ= 70 ± 38, RlMLR= 59 ± 36 cmH2O ⋅ s ⋅ l−1) and El (ElZ= 434 ± 212, ElMLR= 436 ± 210 cmH2O/l) exhibited wide intra- and intersubject variability. Regardless of computation method, Rl was found to decrease as a function of weight, age, respiratory rate (RR), and tidal volume (Vt) whereas it increased as a function of RR ⋅ Vt and inspiratory-to-expiratory time ratio (Ti/Te). El decreased with increasing weight, age, Vt and female gender and increased as RR and Ti/Te increased. We conclude that accounting for the effects of breathing pattern variability and demographic parameters on estimates of Rland El is essential if they are to be of clinical value. Multivariate statistical models of Rl and Elmay facilitate the interpretation of lung mechanics measurements in spontaneously breathing infants.
Renal vasopressin receptor expression and function in rats following spaceflight
Authors: Brooks David P. , Nambi Ponnal , Laping Nicholas J. , Olson Barbara A. , Pullen Mark , Wade Charles E.
Published: December 2017

It has been suggested there is a decreased renal responsiveness to vasopressin following spaceflight and that this may be the mechanism for the increased urine flow that is observed following return to normal gravity. In the present study, we have therefore measured vasopressin receptor expression and activity in kidneys taken from rats 1 and 14 days following spaceflight of 15 days duration. Measurements of renal vasopressin V2 and V1a receptor mRNA expression by quantitative RT-PCR demonstrated little difference at either 1 day or at 14 days following return from space. Evaluation of3H-labeled arginine vasopressin binding to membranes prepared from kidneys indicated that the majority of the vasopressin receptors were V2 receptors. Furthermore, the data suggested that binding to vasopressin V2 or V1areceptors was unaltered at 1 day and 14 days following spaceflight. Similarly, the ability of vasopressin to stimulate adenylate cyclase suggested no change in vasopressin V2 receptor activity in these animals. These data suggest that, whatever changes in fluid and electrolyte metabolism are observed following spaceflight, they are not mediated by changes in vasopressin receptor number or vasopressin-induced stimulation of adenylate cyclase.
Ventilatory and metabolic adaptations to walking and cycling in patients with COPD
Authors: Palange Paolo , Forte Silvia , Onorati Paolo , Manfredi Felice , Serra Pietro , Carlone S.
Published: December 2017

To test the hypothesis that in chronic obstructive pulmonary disease (COPD) patients the ventilatory and metabolic requirements during cycling and walking exercise are different, paralleling the level of breathlessness, we studied nine patients with moderate to severe, stable COPD. Each subject underwent two exercise protocols: a 1-min incremental cycle ergometer exercise (C) and a “shuttle” walking test (W). Oxygen uptake (V˙o 2), CO2output (V˙co 2), minute ventilation (V˙e), and heart rate (HR) were measured with a portable telemetric system. Venous blood lactates were monitored. Measurements of arterial blood gases and pH were obtained in seven patients. Physiological dead space-tidal volume ratio (Vd/Vt) was computed. At peak exercise, W vs. CV˙o 2,V˙e, and HR values were similar, whereasV˙co 2 (848 ± 69 vs. 1,225 ± 45 ml/min; P < 0.001) and lactate (1.5 ± 0.2 vs. 4.1 ± 0.2 meq/l; P < 0.001) were lower, ΔV˙e/ΔV˙co 2(35.7 ± 1.7 vs. 25.9 ± 1.3; P < 0.001) and ΔHR/ΔV˙o 2values (51 ± 3 vs. 40 ± 4; P < 0.05) were significantly higher. Analyses of arterial blood gases at peak exercise revealed higher Vd/Vt and lower arterial partial pressure of oxygen values for W compared with C. In COPD, reduced walking capacity is associated with an excessively high ventilatory demand. Decreased pulmonary gas exchange efficiency and arterial hypoxemia are likely to be responsible for the observed findings.
Historical Perspectives: Physiology in microgravity
Authors: West John B.
Published: December 2017

Studies of physiology in microgravity are remarkably recent, with almost all the data being obtained in the past 40 years. The first human spaceflight did not take place until 1961. Physiological measurements in connection with the early flights were crude, but, in the past 10 years, an enormous amount of new information has been obtained from experiments on Spacelab. The United States and Soviet/Russian programs have pursued different routes. The US has mainly concentrated on relatively short flights but with highly sophisticated equipment such as is available in Spacelab. In contrast, the Soviet/Russian program concentrated on first the Salyut and then the Mir space stations. These had the advantage of providing information about long-term exposure to microgravity, but the degree of sophistication of the measurements in space was less. It is hoped that the International Space Station will combine the best of both approaches. The most important physiological changes caused by microgravity include bone demineralization, skeletal muscle atrophy, vestibular problems causing space motion sickness, cardiovascular problems resulting in postflight orthostatic intolerance, and reductions in plasma volume and red cell mass. Pulmonary function is greatly altered but apparently not seriously impaired. Space exploration is a new frontier with long-term missions to the moon and Mars not far away. Understanding the physiological changes caused by long-duration microgravity remains a daunting challenge.
Central histamine contributed to temperature-induced polypnea in mice
Authors: Izumizaki Masahiko , Iwase Michiko , Kimura Hiroshi , Kuriyama Takayuki , Homma Ikuo
Published: December 2017

Breathing pattern is influenced by body temperature. However, the central mechanism for changing breathing patterns is unknown. Central histamine is involved in heat loss mechanisms in behavioral studies, but little is known about its effect on breathing patterns. We examined first the effect of body temperature on breathing patterns with increasing hypercapnia in conscious mice and then that of the depletion of central histamine by S(+)-α-fluoromethylhistidine hydrochloride (α-FMH) (100 mg/kg ip), a specific inhibitor of histidine decarboxylase, at normal and raised body temperatures. A raised body temperature increased respiratory frequency with reductions in both inspiratory and expiratory time and decreased tidal volume. On the other hand, α-FMH lowered respiratory frequency with a prolongation of expiratory time at the raised temperature; however, this was not observed at a normal temperature. These results indicate that central histamine contributes to an increase in respiratory frequency as a result of a reduction in expiratory time when body temperature is raised.
Effect of carbohydrate ingestion on glucose kinetics and muscle metabolism during intense endurance exercise
Authors: McConell Glenn K. , Canny Benedict J. , Daddo Marcus C. , Nance Marcus J. , Snow Rodney J.
Published: December 2017

There has been recent interest in the potential performance and metabolic effects of carbohydrate ingestion during exercise lasting ∼1 h. In this study, 13 well-trained men ingested in randomized order either a 6% glucose solution (CHO trial) or a placebo (Con trial) during exercise to exhaustion at 83 ± 1% peak oxygen uptake. In six subjects, vastus lateralis muscle was sampled at rest, at 32 min, and at exhaustion, and in six subjects, glucose kinetics was determined by infusion of [6,6-2H]glucose in both trials and ingestion of [6-3H]glucose in the CHO trial. Of the 84 g of glucose ingested during exercise in the CHO trial, only 22 g appeared in the peripheral circulation. This resulted in a small (12 g) but significant ( P < 0.05) increase in glucose uptake without influencing carbohydrate oxidation, muscle glycogen use, or time to exhaustion (CHO: 68.1 ± 4.1 min; Con: 69.6 ± 5.5 min). Decreases in muscle phosphocreatine content and increases in muscle inosine monophosphate and lactate content during exercise were similar in the two trials. Although endogenous glucose production during exercise was partially suppressed in the CHO trial, it remained significantly above preexercise levels throughout exercise. In conclusion, only 26% of the ingested glucose appeared in the peripheral circulation. Glucose ingestion increased glucose uptake and partially reduced endogenous glucose production but had no effect on carbohydrate oxidation, muscle metabolism, or time to exhaustion during exercise at 83% peak oxygen uptake.
Arterial properties of the carotid and femoral artery in endurance-trained and paraplegic subjects
Authors: Schmidt-Trucksäss Arno , Schmid Andreas , Brunner Christian , Scherer Nicole , Zäch Guido , Keul Joseph , Huonker Martin
Published: December 2017

In humans, the relationships of blood flow changes to structure, function, and shear rate of conducting arteries have not been thoroughly examined. Therefore, the purpose of this study was to investigate these parameters of the elastic-type, common carotid artery (CCA) and the muscular-type, common femoral artery (CFA) in long-term highly active and extremely inactive individuals, assuming that the impact of activity-induced blood flow changes on conduit arteries, if any, should be seen in these subjects. We examined 21 highly endurance-trained athletes (A), 10 paraplegic subjects (P), and 20 sedentary subjects (S) by means of noninvasive ultrasound. As a result, the CFA diameter and compliance were highest in A (9.7 ± 0.81 mm; 1.84 ± 0.54 mm2/kPa) and lowest in P (5.9 ± 0.7 mm; 0.54 ± 0.27 mm2/kPa) compared with S (8.3 ± 1.0 mm; 0.92 ± 0.48 mm2/kPa) with P < 0.01 among the groups. Both parameters correlated with each other ( r = 0.62; P < 0.01). Compared with A (378 ± 84 s−1; 37 ± 15 s−1) and S (356 ± 113 s−1; 36 ± 20 s−1), the peak and mean shear rates of the CFA were almost or more than doubled in P (588 ± 120 s−1; 89 ± 26 s−1). In the CCA, only the compliance and peak shear rate showed significant differences among the groups (A: 1.28 ± 0.47 mm2/kPa, 660 ± 138 s−1; S: 1.04 ± 0.27 mm2/kPa, 588 ± 109 s−1; P: 0.65 ± 0.22 mm2/kPa, 490 ± 149 s−1; P < 0.05). In conclusion, the results suggest a structural and functional adaptation in the CFA and a predominantly functional adaptation of the arterial wall properties to differences in the physical activity level and associated exercise-induced blood flow changes in the CCA. The results for humans confirm those from animal experiments. Similar shear rate values of S and P in the CFA support the hypothesis of constant shear stress regulation due to local blood flow changes in humans. On the other hand, the increased shear rate in the CFA in P indicates an at least partially nonphysiological response of the arterial wall in long-term chronic sympathectomy due to a change in local blood flow.
Structure of the primordial diaphragm and defects associated with nitrofen-induced CDH
Authors: Greer John J. , Cote David , Allan Douglas W. , Zhang Wei , Babiuk Randal P. , Ly Linh , Lemke Robert P. , Bagnall Keith
Published: December 2017

The goals of this study were to further our understanding of diaphragm embryogenesis and the pathogenesis of congenital diaphragmatic hernia (CDH). Past work suggests that the pleuroperitoneal fold (PPF) is the primary source of diaphragmatic musculature. Furthermore, defects associated with an animal model of CDH can be traced back to the formation of the PPF. This study was designed to elucidate the anatomic structure of the PPF and to determine which regions of the PPF malform in the well-established nitrofen model of CDH. This was achieved by producing three-dimensional renderings constructed from serial transverse sections of control and nitrofen-exposed rats at embryonic day 13.5. Renderings of left- and right-sided defects demonstrated that the malformations were always limited to the dorsolateral portions of the caudal regions of the PPF. These data provide an explanation of why the holes in diaphragmatic musculature associated with CDH are characteristically located in dorsolateral regions. Moreover, these data provide further evidence against the widely stated hypothesis that a failure of pleuroperitoneal canal closure underlies the pathogenesis of nitrofen-induced CDH.
Denopamine, a β1-adrenergic agonist, increases alveolar fluid clearance in ex vivo rat and guinea pig lungs
Authors: Sakuma Tsutomu , Tuchihara Chiharu , Ishigaki Masanobu , Osanai Kazuhiro , Nambu Yoshihiro , Toga Hirohisa , Takahashi Keiji , Ohya Nobuo , Kurihara Takayuki , Matthay Michael A.
Published: December 2017

The effect of denopamine, a selective β1-adrenergic agonist, on alveolar fluid clearance was determined in both ex vivo rat and guinea pig lungs. Alveolar fluid clearance was measured by the progressive increase in the concentration of Evans blue-labeled albumin over 1 h at 37°C. Denopamine (10−6 to 10−3 M) increased alveolar fluid clearance in a dose-dependent manner in ex vivo rat lungs. Denopamine also stimulated alveolar fluid clearance in guinea pig lungs. Atenolol, a selective β1-adrenergic antagonist, and amiloride, a sodium channel inhibitor, inhibited denopamine-stimulated alveolar fluid clearance. The potency of denopamine was similar to that of similar doses of isoproterenol or terbutaline. Short-term hypoxia (100% nitrogen for 1–2 h) did not alter the stimulatory effect of denopamine. Denopamine (10−4, 10−3 M) increased intracellular adenosine 3′,5′-cyclic monophosphate levels in cultured rat alveolar type II cells. In summary, denopamine, a selective β1-adrenergic agonist, stimulates alveolar fluid clearance in both ex vivo rat and guinea pig lungs.
Fetal lung growth after short-term tracheal occlusion is linearly related to intratracheal pressure
Authors: Kitano Yoshihiro , Von Allmen Daniel , Kanai Masaki , Quinn Theresa M. , Davies Paul , Kitano Yukie , Flake Alan W.
Published: December 2017

Prenatal tracheal occlusion (TO) has been shown to accelerate fetal lung growth, yet the mechanism is poorly understood. The goal of this study was to determine the relationship between fetal intratracheal pressure (Pitr) and fetal lung growth after TO. Fetal lambs underwent placement of an intratracheal catheter and a reference catheter at 115–120 days gestation (term, 145 days). Fetal Pitr was continuously controlled at three levels (high, 8 mmHg; moderate, 4 mmHg; low, 1 mmHg) by a servo-regulated pump. The animals were killed after 4 days, and the parameters of lung growth were compared. Lung volume (136.0 ± 16.7, 94.9 ± 9.7, 55.5 ± 12.4 ml/kg), lung-to-body weight ratio (6.31 ± 0.70, 4.89 ± 0.38, 3.39 ± 0.22%), whole right lung dry weight (3.01 ± 0.29, 2.53 ± 0.15, 2.07 ± 0.24 g/kg), right lung DNA (130.0 ± 11.3, 116.7 ± 8.6, 97.5 ± 10.9 mg/kg), and protein contents (1,865.5 ± 92.5, 1,657.6 ± 106.8, 1,312.0 ± 142.5 mg/kg) in high, moderate, and low groups, respectively, all increased in the moderate compared with the low group and increased further in the high compared with the moderate group. Morphometry confirmed a stepwise increase in the volume of respiratory region and alveolar surface area. We conclude that lung growth in the first 4 days after TO is closely correlated with fetal Pitr, offering additional evidence that an increase in lung expansion is one of the major factors responsible for TO-induced lung growth.
Cerebral gas embolism absorption during hyperbaric therapy: theory
Authors: Branger Annette B. , Lambertsen Christian J. , Eckmann David M.
Published: December 2017

Cerebral gas embolism is a serious consequence of diving. It is associated with decompression sickness and is assumed to cause severe neurological dysfunction. A mathematical model previously developed to calculate embolism absorption time based on in vivo bubble geometry is used in which various conditions of hyperbaric therapy are considered. Effects of varying external pressure and inert gas concentrations in the breathing mixtures, according to US Navy and Royal Navy diving treatment tables, are predicted. Recompression alone is calculated to reduce absorption times of a 50-nl bubble by up to 98% over the untreated case. Lowering the inhaled inert gas concentration from 67.5% to 50% reduces absorption time by 37% at a given pressure. Bubbles formed after diving and decompression with He are calculated to absorb up to 73% faster than bubbles created after diving and decompression with air, regardless of the recompression gas breathed. This model is a useful alternative to impractical clinical trials in assessing which initial step in hyperbaric therapy is most effective in eliminating cerebral gas embolisms should they occur.
Effects of SNP, ouabain, and amiloride on electrical potential profile of isolated sheep pleura
Authors: Hatzoglou C. H. , Gourgoulianis K. I. , Molyvdas P. A.
Published: December 2017

The fluid and solute transport properties of pleural tissue were studied by using specimens of intact visceral and parietal pleura from adult sheep lungs. The samples were transferred to the laboratory in a Krebs-Ringer solution at 4°C within 1 h from the death of the animal. The pleura was then mounted as a planar sheet in a Ussing-type chamber. The results that are presented in this study are the means of six different experiments. The spontaneous potential difference and the inhibitory effects of sodium nitroprusside (SNP), ouabain, and amiloride on transepithelial electrical resistance ( R TE) were measured. The spontaneous potential difference across parietal pleura was 0.5 ± 0.1 mV, whereas that across visceral pleura was 0.4 ± 0.1 mV. R TE of both pleura was very low: 22.02 ± 4.1 Ω · cm2 for visceral pleura and 22.02 ± 3.5 Ω · cm2 for parietal pleura. There was an increase in the R TE when SNP was added to the serosal bathing solution of parietal pleura and to the serosal or mucosal bathing solution in visceral pleura. The same was observed when ouabain was added to the mucosal surface of visceral pleura and to either the mucosal or serosal surface of parietal pleura. Furthermore, there was an increase in R TE when amiloride was added to the serosal bathing solution of parietal pleura. Consequently, the sheep pleura appears to play a role in the fluid and solute transport between the pleural capillaries and the pleural space. There results suggest that there is a Na+ and K+ transport across both the visceral and parietal pleura.
Respiratory mechanics and lung development in the rat from early age to adulthood
Authors: Gomes R. F. M. , Shardonofsky F. , Eidelman D. H. , Bates J. H. T.
Published: December 2017

The purpose of the present study was to establish how the dependence of respiratory mechanics on lung inflation changes during development. We studied seven groups of rats from 10 days to 3 mo of age at five levels of positive end-expiratory pressure (PEEP) from 0 to 7 hPa (1 hPa = 0.1 kPa ≈ 1 cmH2O). At each PEEP level, we measured respiratory system resistance and elastance at both 0.9 and 4.8 Hz to partition the mechanical properties into its airway and tissue components. Elastance increased more rapidly with PEEP in the younger animals, which we interpret as reflecting a more pronounced strain stiffening of the younger parenchyma. However, the decrease in airway resistance with PEEP was more pronounced in the older animals. Morphometric analysis showed that mean tissue density decreased and total alveolar surface area increased with age. Our data suggest that the mechanical interdependence between airways and parenchyma is weaker in very young animals compared with mature animals. This may play a role in the hyperresponsiveness of immaturity.
Assessment of respiratory system mechanics by artificial neural networks: an exploratory study
Authors: Perchiazzi Gaetano , Högman Marieann , Rylander Christian , Giuliani Rocco , Fiore Tommaso , Hedenstierna Göran
Published: December 2017

We evaluated 1) the performance of an artificial neural network (ANN)-based technology in assessing the respiratory system resistance (Rrs) and compliance (Crs) in a porcine model of acute lung injury and 2) the possibility of using, for ANN training, signals coming from an electrical analog (EA) of the lung. Two differently experienced ANNs were compared. One ANN (ANNBIO) was trained on tracings recorded at different time points after the administration of oleic acid in 10 anesthetized and paralyzed pigs during constant-flow mechanical ventilation. A second ANN (ANNMOD) was trained on EA simulations. Both ANNs were evaluated prospectively on data coming from four different pigs. Linear regression between ANN output and manually computed mechanics showed a regression coefficient ( R) of 0.98 for both ANNs in assessing Crs. On Rrs, ANNBIO showed a performance expressed by R= 0.40 and ANNMOD by R = 0.61. These results suggest that ANNs can learn to assess the respiratory system mechanics during mechanical ventilation but that the assessment of resistance and compliance by ANNs may require different approaches.
V˙o 2 and heart rate kinetics in cycling: transitions from an elevated baseline
Authors: Bearden S. E. , Moffatt R. J.
Published: December 2017

The purpose of this study was to examine oxygen consumption (V˙o 2) and heart rate kinetics during moderate and repeated bouts of heavy square-wave cycling from an exercising baseline. Eight healthy, male volunteers performed square-wave bouts of leg ergometry above and below the gas exchange threshold separated by recovery cycling at 35%V˙o 2 peak.V˙o 2 and heart rate kinetics were modeled, after removal of phase I data by use of a biphasic on-kinetics and monoexponential off-kinetics model. Fingertip capillary blood was sampled 45 s before each transition for base excess, HCO[Formula: see text] and lactate concentration, and pH. Base excess and HCO[Formula: see text] concentration were significantly lower, whereas lactate concentration and pH were not different before the second bout. The results confirm earlier reports of a smaller mean response time in the second heavy bout. This was the result of a significantly greater fast-component amplitude and smaller slow-component amplitude with invariant fast-component time constant. A role for local oxygen delivery limitation in heavy exercise transitions with unloaded but not moderate baselines is presented.
Attenuation of skeletal muscle and strength in the elderly: The Health ABC Study
Authors: Goodpaster Bret H. , Carlson Catherine L. , Visser Marjolein , Kelley David E. , Scherzinger Ann , Harris Tamara B. , Stamm Elizabeth , Newman Anne B.
Published: December 2017

Although loss of muscle mass is considered a cause of diminished muscle strength with aging, little is known regarding whether composition of aging muscle affects strength. The skeletal muscle attenuation coefficient, as determined by computed tomography, is a noninvasive measure of muscle density, and lower values reflect increased muscle lipid content. This investigation examined the hypothesis that lower values for muscle attenuation are associated with lower voluntary isokinetic knee extensor strength at 60°/s in 2,627 men and women aged 70–79 yr participating in baseline studies of the Health ABC Study, a longitudinal study of health, aging, and body composition. Strength was higher in men than in women (132.3 ± 34.5 vs. 81.4 ± 22.0 N · m, P < 0.01). Men had greater muscle attenuation values (37.3 ± 6.5 vs. 34.7 ± 7.0 Hounsfield units) and muscle cross-sectional area (CSA) at the midthigh than women (132.7 ± 22.4 vs. 93.3 ± 17.5 cm2, P < 0.01 for both). The strength per muscle CSA (specific force) was also higher in men (1.00 ± 0.21 vs. 0.88 ± 0.21 N · m · cm−2). The attenuation coefficient was significantly lower for hamstrings than for quadriceps (28.7 ± 8.7 vs. 41.1 ± 6.9 Hounsfield units, P < 0.01). Midthigh muscle attenuation values were lowest ( P < 0.01) in the eldest men and women and were negatively associated with total body fat ( r = −0.53, P < 0.01). Higher muscle attenuation values were also associated with greater specific force production ( r = 0.26, P < 0.01). Multivariate regression analysis revealed that the attenuation coefficient of muscle was independently associated with muscle strength after adjustment for muscle CSA and midthigh adipose tissue in men and women. These results demonstrate that the attenuation values of muscle on computed tomography in older persons can account for differences in muscle strength not attributed to muscle quantity.
Simulated microgravity enhances vasoconstrictor responsiveness of rat basilar artery
Authors: Zhang Le-Ning , Zhang Li-Fan , Ma Jin
Published: December 2017

Recently, hypertrophy and increased myogenic tone of brain vessels have been observed in rats after simulated microgravity. It is expected that simulated microgravity may also induce hyperreactivity of brain vessels. To test this hypothesis, Sprague-Dawley rats were subjected to a 4-wk tail-suspended hindlimb unloading (TS) to simulate the cardiovascular deconditioning effect of microgravity. After 4 wk, the vasoreactivity of isolated basilar arterial rings from TS rats to both receptor- and non-receptor-mediated vasoconstrictors, such as KCl, arginine vasopressin, or 5-hydroxytryptamine (5-HT), and vasodilators such as ACh, thrombin, adenosine, or sodium nitroprusside were examined and compared with those from simultaneous control (Cn) rats. In the first part of this study, it was found that the maximal isometric contractile responsiveness evoked by vasoconstrictors such as KCl, arginine vasopressin, or 5-HT was enhanced in basilar arterial rings from TS rats, whereas vasodilatory responsiveness to vasodilators showed no significant difference between TS and Cn rats. In the second part of this study, it was found that removal of the endothelium had no effects on the contractile responsiveness to 5-HT in basilar arterial rings from TS rats but enhanced markedly the responsiveness in basilar arterial rings from Cn rats to an extent comparable with that of TS rats. Application of tetraethylammonium also had no effects on the contractile response to 5-HT in basilar arterial rings from TS but significantly increased the responsiveness of basilar arterial rings from Cn rats with endothelium intact. These results showed that 4-wk simulated microgravity enhanced the vascular contractile responsiveness of basilar arterial rings to both receptor- and non-receptor-mediated vasoconstrictors, and the enhancement of 5-HT-induced contraction in TS rat basilar arteries was due to an impairment of endothelium-dependent mechanism. These results suggest that endothelium-derived hyperpolarizing factors are responsible for this endothelium-dependent attenuating modulatory mechanism in contractile responsiveness of rat basilar arteries to 5-HT.
Fatty acid oxidation in African-American and Caucasian women during physical activity
Authors: Hickner R. C. , Privette J. , McIver K. , Barakat H.
Published: December 2017

The goal of this study was to determine whether differences in physical activity-related fat oxidation exist between lean and obese African-American (LAA and OAA) and lean and obese Caucasian (LC and OC) premenopausal women. Lean AA (28.4 ± 2.8 yr, n = 7), LC (24.7 ± 1.8 yr, n = 9), OAA (30.9 ± 2.2 yr, n = 11), and OC (34.1 ± 2.5 yr, n = 9) women underwent preliminary assessment of peak aerobic capacity (V˙o 2 peak). On a subsequent testing day, participants exercised after an 8-h fast on a cycle ergometer at 15 W (∼40% V˙o 2 peak) for 10 min and then for 10 min at ∼65% V˙o 2 peak. Fatty acid oxidation was determined using the average respiratory exchange ratio and O2 consumption during minutes 5–9of the exercise session. Percent body fat and fat-free mass were lower ( P < 0.05) in LAA (25.8 ± 2.8% and 48.3 kg) and LC (26.4 ± 2.0% and 45.8 ± 1.7 kg) than in OAA (41.2 ± 1.3% and 58.8 ± 3.3 kg) and OC (39.3 ± 2.7% and 58.6 kg) women. Fat oxidation among the groups was analyzed statistically using analysis of covariance with fat-free mass andV˙o 2 peak as covariates. During exercise at 15 W, fat oxidation was as low in LAA (0.134 ± 0.024 g/min) as in OAA (0.144 ± 0.026 g/min) and OC (0.156 ± 0.020 g/min) women: all these rates of fat oxidation were lower than in LC women (0.200 ± 0.021 g/min, P < 0.05, LC vs. all other groups). Fatty acid oxidation during higher-intensity exercise (65%V˙o 2 peak) was higher in LC than in OC women but was not statistically different between African-American and Caucasian groups. Fatty acid oxidation was therefore lower during low-intensity physical activity in OAA, LAA, and OC than in LC women.
Effect of prior high-intensity exercise on exercise-induced arterial hypoxemia in Thoroughbred horses
Authors: Manohar Murli , Goetz Thomas E. , Hassan Aslam S.
Published: December 2017

Strenuously exercising horses exhibit arterial hypoxemia and exercise-induced pulmonary hemorrhage (EIPH), the latter resulting from stress failure of pulmonary capillaries. The present study was carried out to examine whether the structural changes in the blood-gas barrier caused by a prior bout of high-intensity short-term exercise capable of inducing EIPH would affect the arterial hypoxemia induced during a successive bout of exercise performed at the same workload. Two sets of experiments, double- and single-exercise-bout experiments, were carried out on seven healthy, sound Thoroughbred horses. Experiments were carried out in random order, 7 days apart. In the double-exercise experiments, horses performed two successive bouts (each lasting 120 s) of galloping at 14 m/s on a 3.5% uphill grade, separated by an interval of 6 min. Exertion at this workload induced arterial hypoxemia within 30 s of the onset of galloping as well as desaturation of Hb, a progressive rise in arterial Pco2, and acidosis as exercise duration increased from 30 to 120 s. In the single-exercise-bout experiments, blood-gas/pH data resembled those from the first run of the double-exercise experiments, and all horses experienced EIPH. Thus, in the double-exercise experiments, before the horses performed the second bout of galloping at 14 m/s on a 3.5% uphill grade, stress failure of pulmonary capillaries had occurred. Although arterial hypoxemia developed during the second run, arterial Po2values were significantly ( P < 0.01) higher than in the first run. Thus prior exercise not only failed to accentuate the severity of arterial hypoxemia, it actually diminished the magnitude of exercise-induced arterial hypoxemia. The decreased severity of exercise-induced arterial hypoxemia in the second run was due to an associated increase in alveolar Po2, as arterial Pco2was significantly lower than in the first run. Thus our data do not support a role for structural changes in the blood-gas barrier related to the stress failure of pulmonary capillaries in causing the exercise-induced arterial hypoxemia in horses.
Selected Contribution: Improved anoxic tolerance in rat diaphragm following intermittent hypoxia
Authors: Clanton Thomas L. , Wright Valerie P. , Reiser Peter J. , Klawitter Paul F. , Prabhakar Nanduri R.
Published: December 2017

Intermittent hypoxia (IH), associated with obstructive sleep apnea, initiates adaptive physiological responses in a variety of organs. Little is known about its influence on diaphragm. IH was simulated by exposing rats to alternating 15-s cycles of 5% O2 and 21% O2 for 5 min, 9 sets/h, 8 h/day, for 10 days. Controls did not experience IH. Diaphragms were excised 20–36 h after IH. Diaphragm bundles were studied in vitro or analyzed for myosin heavy chain isoform composition. No differences in maximum tetanic stress were observed between groups. However, peak twitch stress ( P < 0.005), twitch half-relaxation time ( P < 0.02), and tetanic stress at 20 or 30 Hz ( P < 0.05) were elevated in IH. No differences in expression of myosin heavy chain isoforms or susceptibility to fatigue were seen. Contractile function after 30 min of anoxia (95% N2-5% CO2) was markedly preserved at all stimulation frequencies during IH and at low frequencies after 15 min of reoxygenation. Anoxia-induced increases in passive muscle force were eliminated in the IH animals ( P < 0.01). These results demonstrate that IH induces adaptive responses in the diaphragm that preserve its function in anoxia.
Cytokine changes after a marathon race
Authors: Nieman David C. , Henson Dru A. , Smith Lucille L. , Utter Alan C. , Vinci Debra M. , Davis J. Mark , Kaminsky David E. , Shute Max
Published: December 2017

The influence of carbohydrate (1 l/h of a 6% carbohydrate beverage), gender, and age on pro- and anti-inflammatory plasma cytokine and hormone changes was studied in 98 runners for 1.5 h after two competitive marathon races. The marathoner runners were randomly assigned to carbohydrate (C, n = 48) and placebo (P, n = 50) groups, with beverages administered during the races in a double-blind fashion using color codes. Plasma glucose was higher and cortisol was lower in the C than in the P group after the race ( P < 0.001). For all subjects combined, plasma levels of interleukin (IL)-10, IL-1 receptor antagonist (IL-1ra), IL-6, and IL-8 rose significantly immediately after the race and remained above prerace levels 1.5 h later. The pattern of change in all cytokines did not differ significantly between the 12 women and 86 men in the study and the 23 subjects ≥50 yr of age and the 75 subjects <50 yr of age. The pattern of change in IL-10, IL-1ra, and IL-8, but not IL-6, differed significantly between the C and the P group, with higher postrace values measured for IL-10 (109% higher) and IL-1ra (212%) in the P group and for IL-8 (42%) in the C group. In conclusion, plasma levels of IL-10, IL-1ra, IL-6, and IL-8 rose strongly in runners after a competitive marathon, and this was not influenced by age or gender. Carbohydrate ingestion, however, had a major effect in attenuating increases in cortisol and two anti-inflammatory cytokines, IL-10 and IL-1ra.
General characteristics of the sigmoidal model equation representing quasi-static pulmonary P-V curves
Authors: Narusawa Uichiro
Published: December 2017

A pulmonary pressure-volume (P-V) curve represented by a sigmoidal model equation with four parameters, V(P) = a + b{1 + exp[−(P − c)/d]}−1, has been demonstrated to fit inflation and deflation data obtained under a variety of conditions extremely well. In the present report, a differential equation on V(P) is identified, thus relating the fourth parameter, d, to the difference between the upper and the lower asymptotes of the volume, b, through a proportionality constant, α, with its order of magnitude of 10−4to 10−5(in ml−1· cmH2O−1). When the model equation is normalized using a nondimensional volume, V̄(−1 < V̄ < 1), and a nondimensional pressure, P̄(=(p/c) − 1), the resulting P̄-V̄ curve depends on a single nondimensional parameter, Λ = αbc. A nondimensional work of expansion/compression,W̄1–2, is also obtained along the quasi-static sigmoidal P-V curve between an initial volume (at 1) and a final volume (at 2). Six sets of P-V data available in the literature are used to show the changes that occur in these two parameters (Λ defining the shape of the sigmoidal curve and W̄1–2accounting for the range of clinical data) with different conditions of the total respiratory system. The clinical usefulness of these parameters requires further study.
Purine salvage to adenine nucleotides in different skeletal muscle fiber types
Authors: Brault Jeffrey J. , Terjung Ronald L.
Published: December 2017

Rates of purine salvage of adenine and hypoxanthine into the adenine nucleotide (AdN) pool of the different skeletal muscle phenotype sections of the rat were measured using an isolated perfused hindlimb preparation. Tissue adenine and hypoxanthine concentrations and specific activities were controlled over a broad range of purine concentrations, ranging from 3 to 100 times normal, by employing an isolated rat hindlimb preparation perfused at a high flow rate. Incorporation of [3H]adenine or [3H]hypoxanthine into the AdN pool was not meaningfully influenced by tissue purine concentration over the range evaluated (∼0.10–1.6 μmol/g). Purine salvage rates were greater ( P < 0.05) for adenine than for hypoxanthine (35–55 and 20–30 nmol · h−1 · g−1, respectively) and moderately different ( P < 0.05) among fiber types. The low-oxidative fast-twitch white muscle section exhibited relatively low rates of purine salvage that were ∼65% of rates in the high-oxidative fast-twitch red section of the gastrocnemius. The soleus muscle, characterized by slow-twitch red fibers, exhibited a high rate of adenine salvage but a low rate of hypoxanthine salvage. Addition of ribose to the perfusion medium increased salvage of adenine (up to 3- to 6-fold, P < 0.001) and hypoxanthine (up to 6- to 8-fold, P < 0.001), depending on fiber type, over a range of concentrations up to 10 mM. This is consistent with tissue 5-phosphoribosyl-1-pyrophosphate being rate limiting for purine salvage. Purine salvage is favored over de novo synthesis, inasmuch as delivery of adenine to the muscle decreased ( P < 0.005) de novo synthesis of AdN. Providing ribose did not alter this preference of purine salvage pathway over de novo synthesis of AdN. In the absence of ribose supplementation, purine salvage rates are relatively low, especially compared with the AdN pool size in skeletal muscle.