bluuebunny/crossref_metadata_2025 huggingface dataset:
Simulated microgravity increases myogenic tone in rat cerebral arteries
Authors: Geary Greg G. , Krause Diana N. , Purdy Ralph E. , Duckles Sue P.
Published: December 2017

Adaptation of the cerebral circulation to microgravity was investigated in rat middle cerebral arteries after 20 days of hindlimb unweighting (HU). Myogenic responses were measured in isolated, pressurized arteries from HU and control animals. Maximal passive lumen diameters, obtained in the absence of extracellular Ca2+ plus EDTA, were not significantly different between groups (249 vs. 258 μm). In physiological salt solution, arteries from both HU and control animals maintained a constant lumen diameter when subjected to incremental increases in transmural pressure (20–80 mmHg). However, the diameter of arteries from HU animals was significantly smaller than that of arteries from control animals at all pressures; this difference could be eliminated by exposure to the nitric oxide synthase inhibitor N G-nitro-l-arginine methyl ester. After HU treatment, transient distensibility of the artery wall in response to pressure was also significantly decreased, whereas the frequency and amplitude of vasomotion were increased. The latter changes were not affected by N G-nitro-l-arginine methyl ester. Thus simulated microgravity increases cerebral artery myogenic tone through both nitric oxide synthase-dependent and -independent mechanisms.
A murine skeletal muscle ischemia-reperfusion injury model: differential pathology in BALB/c and DBA/2N mice
Authors: Carter W. O. , Bull C. , Bortolon E. , Yang L. , Jesmok G. J. , Gundel R. H.
Published: December 2017

Ischemia-reperfusion injuries can occur with diseases such as myocardial infarction and stroke and during surgical procedures such as organ transplantation and correction of aortic aneurysms. We developed a murine model to mimic abdominal aortic aneurysm repair with cross-clamping of the aorta distal to the renal artery. After model development, we compared the normal complement BALB/c mouse with the C5-deficient DBA/2N mouse. To assess quantitative differences, we measured neuromuscular function up to 72 h after ischemia with a subjective clinical scoring system, as well as plasma chemistries, hematology, and histopathology. There were significant increases in clinical scores and creatine phosphokinase, lactate dehydrogenase, and muscle histopathology scores in BALB/c mice compared with those in DBA/2N mice and sham-surgery mice. Muscle histopathology scores of the cranial tibialis and quadriceps correlated well with clinical signs, creatine phosphokinase, and lactate dehydrogenase, and indicated the greatest pathology in these muscle groups. We developed a murine model of skeletal muscle ischemia-reperfusion injury that can utilize the benefits of murine genetic and transgenic models to assess therapeutic principles of this model. Additionally, we have shown a significant reduction in clinical signs, plasma muscle enzyme concentrations, and muscle pathology in the C5-deficient DBA/2N mouse in this model.
Dopamine, sensory discharge, and stimulus interaction with CO2 and O2 in cat carotid body
Authors: Buerk D. G. , Osanai S. , Mokashi A. , Lahiri S.
Published: December 2017

It is hypothesized that carotid body chemosensory activity is coupled to neurosecretion. The purpose of this study was to examine whether there was a correspondence between carotid body tissue dopamine (DA) levels and neuronal discharge (ND) measured from the carotid sinus nerve of perfused cat carotid bodies and to characterize interaction between CO2 and O2 in these responses. ND and tissue DA were measured after changing from normoxic, normocapnic control bicarbonate buffer ([Formula: see text]>120 Torr, [Formula: see text] 25–30 Torr, pH ∼ 7.4) to normoxic hypercapnia ([Formula: see text] 55–57 Torr, pH 7.1–7.2) or to hypoxic solutions ([Formula: see text] 30–35 Torr) with normocapnia ([Formula: see text] 25–30 Torr, pH ∼ 7.4) or hypocapnia ([Formula: see text]10–15 Torr, pH 7.6–7.8). Similar temporal changes for ND and tissue DA were found for all of the stimuli, although there was a much different proportional relationship for normoxic hypercapnia. Both ND and DA increased above baseline values during flow interruption and normocapnic hypoxia, and both decreased below baseline values during hypoxic hypocapnia. In contrast, normoxic hypercapnia caused an initial increase in ND, from a baseline of 175 ± 12 (SE) to a peak of 593 ± 20 impulses/s within 4.6 ± 0.9 s, followed by adaptation, whereas ND declined to 423 ± 20 impulses/s after 1 min. Tissue DA initially increased from a baseline of 17.9 ± 1.2 μM to a peak of 23.2 ± 1.2 μM within 3.0 ± 0.7 s, then declined to 2.6 ± 1.0 μM. The substantial decrease in tissue DA during normoxic hypercapnia was not consistent with the parallel changes in DA with ND that were observed for hypoxic stimuli.
Small bowel tonometry is more accurate than gastric tonometry in detecting gut ischemia
Authors: Walley Keith R. , Friesen Byron P. , Humer Michael F. , Phang P. Terry
Published: December 2017

Gastric tonometer[Formula: see text] measurement may help identify gut ischemia in critically ill patients but is frequently associated with large measurement errors. We tested the hypothesis that small bowel tonometer [Formula: see text]measurement yields more accurate information. In 10 anesthetized, mechanically ventilated pigs subject to progressive hemorrhage, we measured gut oxygen delivery and consumption. We also measured tonometer [Formula: see text] minus arterial[Formula: see text]([Formula: see text]) and calculated the corresponding intracellular pH from tonometers placed in the stomach and jejunum. We found that the correlation coefficient ( r 2) for biphasic gut oxygen delivery-[Formula: see text]relationships was 0.29 ± 0.52 for the gastric tonometer vs. 0.76 ± 0.25 for the small bowel tonometer ( P < 0.05). In addition, the critical gastric tonometer [Formula: see text]was excessively high and variable (62.9 ± 39.6) compared with the critical small bowel tonometer[Formula: see text] (17.0 ± 15.0, P < 0.01). Small bowel tonometer[Formula: see text] was closely correlated with superior mesenteric vein [Formula: see text]( r 2 = 0.81, P < 0.001), whereas gastric tonometer [Formula: see text] was not ( r 2 = −0.13, P = not significant). We conclude that measurement of gastric tonometer[Formula: see text] yields excessively noisy and inaccurate data on the onset of gut anaerobic metabolism in hemorrhagic shock. Small bowel tonometer [Formula: see text] is less noisy and, as a result, is superior in detecting gut hypoperfusion and the onset of anaerobic metabolism.
Fuel metabolism in men and women during and after long-duration exercise
Authors: Horton Tracy J. , Pagliassotti Michael J. , Hobbs Karen , Hill James O.
Published: December 2017

This study aimed to determine gender-based differences in fuel metabolism in response to long-duration exercise. Fuel oxidation and the metabolic response to exercise were compared in men ( n = 14) and women ( n = 13) during 2 h (40% of maximal O2 uptake) of cycling and 2 h of postexercise recovery. In addition, subjects completed a separate control day on which no exercise was performed. Fuel oxidation was measured using indirect calorimetry, and blood samples were drawn for the determination of circulating substrate and hormone levels. During exercise, women derived proportionally more of the total energy expended from fat oxidation (50.9 ± 1.8 and 43.7 ± 2.1% for women and men, respectively, P < 0.02), whereas men derived proportionally more energy from carbohydrate oxidation (53.1 ± 2.1 and 45.7 ± 1.8% for men and women, respectively, P < 0.01). These gender-based differences were not observed before exercise, after exercise, or on the control day. Epinephrine ( P < 0.007) and norepinephrine ( P < 0.0009) levels were significantly greater during exercise in men than in women (peak epinephrine concentrations: 208 ± 36 and 121 ± 15 pg/ml in men and women, respectively; peak norepinephrine concentrations: 924 ± 125 and 659 ± 68 pg/ml in men and women, respectively). As circulating glycerol levels were not different between the two groups, this suggests that women may be more sensitive to the lipolytic action of the catecholamines. In conclusion, these data support the view that different priorities are placed on lipid and carbohydrate oxidation during exercise in men and women and that these gender-based differences extend to the catecholamine response to exercise.
Effects of inspiratory and expiratory positive pressure difference on airflow dynamics during sleep
Authors: Sériès F. , Marc I.
Published: December 2017

We measured the effects of dissociating inspiratory and expiratory positive pressure (Pi and Pe, respectively) on the inspiratory flow limitation pattern and on genioglossus (GG) activity in nine sleep apnea patients. Measurements were made at two different levels of Pi with stepwise increases in Pe. Flow-limited breaths were observed during each recording session. In six of nine subjects, maximal inspiratory flow (V˙i max) was correlated with the difference between Pi and Pe (correlations were negative in 5 subjects, positive in 1 subject). In three other patients,V˙i maxwas not influenced by the amount of pressure difference. A positive relationship between tonic and/or phasic GG electromyographic activities and Pi-Pedifference was observed at least at one Pi level in all patients. This correlation was observed independently of the presence or absence of any relationship betweenV˙i maxand the amount of pressure difference. Our results suggest that increasing the Pi-Pedifference (i.e., decreasing Pe) may be associated with a significant worsening in inspiratory flow limitation and that theV˙i max-pressure difference behavior is not dependent on the GG electromyographic-pressure response.
Expression of acetylcholine receptor mRNAs in atrophying and nonatrophying skeletal muscles of old rats
Authors: Gomes Ronald R. , Booth Frank W.
Published: December 2017

We examined the age-related association in skeletal muscle between atrophy and expression of mRNAs encoding both the γ-subunit of the nicotinic acetylcholine receptor (AChR), and myogenin, a transcription factor that upregulates expression of the γ-subunit promoter. Gastrocnemius and biceps brachii muscles were collected from young (2-mo-old), adult (18-mo-old), and old (31-mo-old) Fischer 344/Brown Norway F1 generation cross male rats. In the gastrocnemius muscles of old vs. young and adult rats, lower muscle mass was accompanied by significantly elevated AChR γ-subunit and myogenin mRNA levels. In contrast, the biceps brachii muscle exhibited neither atrophy nor as drastic a change in AChR γ-subunit and myogenin mRNA levels with age. Expression of the AChR ε-subunit mRNA did not change with age in either gastrocnemius or biceps brachii muscles. Thus changes in skeletal muscle AChR γ-subunit and myogenin mRNA levels may be more related to atrophy than to chronological age in old rats.
Cardiovascular and Valsalva responses during parabolic flight
Authors: Schlegel Todd T. , Benavides Edgar W. , Barker Donald C. , Brown Troy E. , Harm Deborah L. , DeSilva Suresh J. , Low Phillip A.
Published: December 2017

We investigated the integrated cardiovascular responses of 15 human subjects to the acute gravitational changes (micro- and hypergravity portions) of parabolic flight. Measurements were made with subjects quietly seated and while subjects performed controlled Valsalva maneuvers. During quiet, seated, parabolic flight, mean arterial pressure increased during the transition into microgravity but decreased as microgravity was sustained. The decrease in mean arterial pressure was accompanied by immediate reflexive increases in heart rate but by absent (or later-than-expected) reflexive increases in total vascular resistance. Mean arterial pressure responses in Valsalva phases IIl, III, and IV were accentuated in hypergravity relative to microgravity ( P < 0.01, P < 0.01, and P < 0.05, respectively), but accentuations differed qualitatively and quantitatively from those induced by a supine-to-seated postural change in 1 G. This study is the first systematic evaluation of temporal and Valsalva-related changes in cardiovascular parameters during parabolic flight. Results suggest that arterial baroreflex control of vascular resistance may be modified by alterations of cardiopulmonary, vestibular, and/or other receptor activity.
Instrumentation for the remote monitoring of physiological and behavioral variables
Authors: Andrews R. D.
Published: December 2017

Few commercial products are available for investigators who wish to monitor multiple physiological and behavioral variables in unrestrained subjects. When telemetry is not practical, e.g., in studies of at-sea diving physiology, one of the only options is to design and build a custom data-logging instrument. This paper describes how a data logger was developed for the successful long-term monitoring of dive depth, swim speed, heart rate, water temperature, and multiple body temperatures from free-ranging northern elephant seals. The task was facilitated by using a commercially available single-board computer designed specifically for portable multichannel data acquisition and, where possible, off-the-shelf sensors/transducers available with integrated signal-conditioning circuits. A smaller data logger for monitoring the electrocardiogram, body temperature, and dive behavior of double-crested cormorants is also described to illustrate the flexibility and simplicity of this approach. Although it is customized for diving animals, with incorporation of the appropriate sensors the basic design should be applicable to studies of comparative, environmental, or exercise physiology involving most medium-to-large animals, including humans.
Effects of changes in pH and CO2 on pulmonary arterial wall tension are not endothelium dependent
Authors: Sweeney Michèle , Beddy David , Honner Valerie , Sinnott Bridget , O’Regan Ronan G. , McLoughlin Paul
Published: December 2017

We examined the changes in isolated pulmonary artery (PA) wall tension on switching from control conditions (pH 7.38 ± 0.01,[Formula: see text] 32.9 ± 0.4 Torr) to isohydric hypercapnia (pH change 0.00 ± 0.01,[Formula: see text] change 24.9 ± 1.1 Torr) or normocapnic acidosis (pH change −0.28 ± 0.01,[Formula: see text] change −0.3 ± 0.04 Torr) and the role of the endothelium in these responses. In rat PA, submaximally contracted with phenylephrine, isohydric hypercapnia did not cause a significant change in mean (± SE) tension [3.0 ± 1.8% maximal phenylephrine-induced tension (Po)]. Endothelial removal did not alter this response. In aortic preparations, isohydric hypercapnia caused significant ( P < 0.01) relaxation (−27.4 ± 3.2% Po), which was largely endothelium dependent. Normocapnic acidosis caused relaxation of PA (−20.2 ± 2.6% Po), which was less ( P < 0.01) than that observed in aortic preparations (−35.7 ± 3.4% Po). Endothelial removal left the pulmonary response unchanged while increasing ( P < 0.01) the aortic relaxation (−53.1 ± 4.4% Po). These data show that isohydric hypercapnia does not alter PA tone. Reduction of PA tone in normocapnic acidosis is endothelium independent and substantially less than that of systemic vessels.
Grip strength changes over 27 yr in Japanese-American men
Authors: Rantanen T. , Masaki K. , Foley D. , Izmirlian G. , White L. , Guralnik J. M.
Published: December 2017

The aim of this study was to describe changes in grip strength over a follow-up period of ∼27 yr and to study the associations of rate of strength decline with weight change and chronic conditions. The data are from the Honolulu Heart Program, a prospective population-based study established in 1965. Participants at exam 1 were 8,006 men (ages 45–68 yr) who were of Japanese ancestry and living in Hawaii. At follow-up, 3,741 men (age range, 71–96 yr) participated. Those who died before the follow-up showed significantly lower grip-strength values at baseline than did the survivors. The average annualized strength change among the survivors was −1.0%. Steeper decline (>1.5%/yr) was associated with older age at baseline, greater weight decrease, and chronic conditions such as stroke, diabetes, arthritis, coronary heart disease, and chronic obstructive pulmonary disease. The risk factors for having very low hand-grip strength at follow-up, here termed grip-strength disability (≤21 kg, the lowest 10th percentile), were largely same as those for steep strength decline. However, the age-adjusted correlation between baseline and follow-up strength was strong ( r = 0.557, P < 0.001); i.e., those who showed greater grip strength at baseline were also likely to do so 27 yr later. Consequently, those in the lowest grip-strength tertile at baseline had about eight times greater risk of grip-strength disability than those in the highest tertile because of their lower reserve of strength. In old age, maintenance of optimal body mass may help prevent steep strength decrease and poor absolute strength.
Effects of the ovarian cycle on sympathetic neural outflow during static exercise
Authors: Ettinger Steven M. , Silber David H. , Gray Kristen S. , Smith Michael B. , Yang Qing X. , Kunselman Allen R. , Sinoway Lawrence I.
Published: December 2017

We compared reflex responses to static handgrip at 30% maximal voluntary contraction (MVC) in 10 women (mean age 24.1 ± 1.7 yr) during two phases of their ovarian cycle: the menstrual phase ( days 1–4) and the follicular phase ( days 10–12). Changes in muscle sympathetic nerve activity (MSNA; microneurography) in response to static exercise were greater during the menstrual compared with follicular phase (phase effect P = 0.01). Levels of estrogen were less during the menstrual phase (75 ± 5.5 vs. 116 ± 9.6 pg/ml, days 1–4 vs. days 10–12; P = 0.002). Generated tension did not explain differences in MSNA responses (MVC: 29.3 ± 1.3 vs. 28.2 ± 1.5 kg, days 1–4 vs. days 10–12; P = 0.13). In a group of experiments with the use of31P-NMR spectroscopy, no phase effect was observed for H+and[Formula: see text] concentrations ( n = 5). During an ischemic rhythmic handgrip paradigm (20% MVC), a phase effect was not observed for MSNA or H+or[Formula: see text] concentrations, suggesting that blood flow was necessary for the expression of the cycle-related effect. The present studies suggest that, during static handgrip exercise, MSNA is increased during the menstrual compared with the follicular phase of the ovarian cycle.
Shortening and [Ca2+] dynamics of left ventricular myocytes isolated from exercise-trained rats
Authors: Palmer Bradley M. , Thayer Anne M. , Snyder Steven M. , Moore Russell L.
Published: December 2017

The effects of run endurance training and fura 2 loading on the contractile function and Ca2+ regulation of rat left ventricular myocytes were examined. In myocytes not loaded with fura 2, the maximal extent of myocyte shortening was reduced with training under our pacing conditions [0.5 Hz at 2.0 and 0.75 mM external Ca2+ concentration ([Ca2+]o)], although training had no effect on the temporal characteristics. The “light” loading of myocytes with fura 2 markedly suppressed (∼50%) maximal shortening in the sedentary and trained groups, although the temporal characteristics of myocyte shortening were significantly prolonged in the trained group. No discernible differences in the dynamic characteristics of the intracellular Ca2+ concentration ([Ca2+]) transient were detected at 2.0 mM [Ca2+]o, although peak [Ca2+] and rate of [Ca2+] rise during caffeine contracture were greater in the trained state at 0.75 mM [Ca2+]o. We conclude that training induced a diminished myocyte contractile function under the conditions studied here and a more effective coupling of inward Ca2+ current to sarcoplasmic reticulum Ca2+ release at low [Ca2+]o, and that fura 2 and its loading vehicle DMSO significantly alter the intrinsic characteristics of myocyte contractile function and Ca2+ regulation.
Novel transitions in MHC isoforms: separate and combined effects of thyroid hormone and mechanical unloading
Authors: Caiozzo Vincent J. , Baker Michael J. , Baldwin Kenneth M.
Published: December 2017

Single-fiber ( n = 3,818 fibers) electrophoretic analyses were used to delineate the separate and combined effects of hyperthyroidism (T3) and hindlimb suspension (HS) on the myosin heavy chain (MHC) isoform composition (1-, 2-, and 4-wk time points) of the rat soleus muscle. The key findings of this study are as follows. First, T3and HS both altered the distribution of MHC isoforms at the single-fiber level; however, the populations of fibers produced by these two interventions were clearly different from one another. Second, T3+ HS rapidly converted the soleus into a fast muscle, producing large increases in the relative contents of the fast type IIx and IIb MHC isoforms which were primarily expressed in several populations of hybrid fibers (e.g., types I/IIa/IIx, I/IIx/IIb, I/IIa/IIx/IIb). Finally, T3+ HS produced unique populations of hybrid fibers that did not adhere to the I↔IIa↔IIx↔IIb sequential scheme of MHC plasticity. Collectively, the findings of this study demonstrate that the intervention of T3+ HS is a powerful model for manipulating and studying MHC isoform plasticity in slow skeletal muscle.
Characteristics of the infant arousal response
Authors: McNamara Frances , Wulbrand Henning , Thach Bradley T.
Published: December 2017

Arousal is considered to be an important response to a life-threatening stimulus. Recently, it has been shown that the infant arousal response to an elevated inspired CO2 level occurs as a sequence of events involving presumptive brain stem responses before awakening (A. Lijowska, N. Reed, B. Chiodini, and B. T. Thach. Am. J. Respir. Crit. Care Med. 151: A151, 1995; A. S. Lijowska, N. W. Reed, B. A. Mertins Chiodini, and B. T. Thach. J. Appl. Physiol. 83: 219–228, 1997). We wanted to further evaluate the relationship of subcortical reflexes to cortical arousal in infants. We used a nonrespiratory (tactile) stimulus to elicit arousal in infants during non-rapid-eye-movement (NREM) and rapid-eye-movement (REM) sleep. We found that a tactile stimulus elicited an arousal sequence that commenced with a spinal withdrawal reflex, was followed by brain stem responses (respiratory and startle responses), and ended in a cortical arousal. The entire pathway or part of it in the order of spinal to cortical responses could be elicited. REM and NREM responses were similar except for significant differences in the latencies of spinal and subcortical reflexes. These observations suggest that the infant arousal response to a tactile stimulus involves a progression of central nervous system activation from the spinal to cortical levels. The different components of the arousal pathway may be important for an infant to respond appropriately to stimuli during sleep without necessarily disturbing sleep.
Pulmonary embolization causes hypoxemia by redistributing regional blood flow without changing ventilation
Authors: Altemeier William A. , Robertson H. Thomas , McKinney Steve , Glenny Robb W.
Published: December 2017

To explore mechanisms of hypoxemia after acute pulmonary embolism, we measured regional pulmonary blood flow and alveolar ventilation before and after embolization with 780-μm beads in five anesthetized, mechanically ventilated pigs. Regional ventilation and perfusion were determined in ∼2.0-cm3 lung volumes by using 1-μm-diameter aerosolized and 15-μm-diameter injected fluorescent microspheres. Hypoxemia after embolization resulted from increased perfusion to regions with low ventilation-to-perfusion ratios. Embolization caused an increase in perfusion heterogeneity and a fall in the correlation between ventilation and perfusion. Correlation between regional ventilation pre- and postembolization was greater than correlation between regional perfusion pre- and postembolization. The majority of regional ventilation-to-perfusion ratio heterogeneity was attributable to changes in regional perfusion. Regional perfusion redistribution without compensatory changes in regional ventilation is responsible for hypoxemia after pulmonary vascular embolization in pigs.
Brain stem lesion size determined by DEAD red or conjugation of neurotoxin to fluorescent beads
Authors: Nattie Eugene E. , Erlichman Joseph S. , Li Aihua
Published: December 2017

Neurotoxin microinjected into the retrotrapezoid nucleus of anesthetized rats decreases phrenic activity and eliminates the response to CO2. In unanesthetized rats, such treatment has no effect on awake, resting breathing and decreases CO2 sensitivity by 40% (M. Akilesh, M. Kamper, A. Li, and E. E. Nattie. J. Appl. Physiol. 82: 469–479, 1997). One important factor in explaining these disparate results is the actual size of the anatomic lesion. In the present study, we injected ibotenic acid into the retrotrapezoid nucleus of anesthetized rats and evaluated lesion size by using two new approaches: 1) DEAD red, a fluorescent probe that enters impaired cells through leaky membranes and binds to nucleic acids, and 2) conjugation of toxin to fluorescent beads. With the use of DEAD red, the region containing labeled dying cells was 313 ± 104 nl ( n = 4), six times larger than the initial injected volume, and the physiological effects on phrenic amplitude, the CO2 response, and blood pressure began within minutes and were substantial. With conjugated toxin, in theory, neuronal damage would be limited to the region of detectable fluorescence (49 ± 10 nl; n = 4). Effects on phrenic amplitude, CO2 sensitivity, and blood pressure were absent until ∼2 h postinjection. Control experiments, with 2 h of in vitro incubation of the neurotoxin-microbead conjugate and injection of the supernatant after centrifugation, showed similar results that suggest release of conjugated neurotoxin. We conclude that DEAD red provides a useful means to monitor neuronal impairment in acute studies in vivo. Conjugation of neurotoxin to microbeads may be less reliable in this regard.
Mast cell activation is not required for induction of airway hyperresponsiveness by ozone in mice
Authors: Noviski N. , Brewer J. P. , Skornik W. A. , Galli S. J. , Drazen J. M. , Martin T. R.
Published: December 2017

Exposure to ambient ozone (O3) is associated with increased exacerbations of asthma. We sought to determine whether mast cell degranulation is induced by in vivo exposure to O3in mice and whether mast cells play an essential role in the development of pulmonary pathophysiological alterations induced by O3. For this we exposed mast cell-deficient WBB6F1- kitW/ kitW-v( kitW/ kitW-v) mice and the congenic normal WBB6F1(+/+) mice to air or to 1 or 3 parts/million O3for 4 h and studied them at different intervals from 4 to 72 h later. We found evidence of O3-induced cutaneous, as well as bronchial, mast cell degranulation. Polymorphonuclear cell influx into the pulmonary parenchyma was observed after exposure to 1 part/milllion O3only in mice that possessed mast cells. Airway hyperresponsiveness to intravenous methacholine measured in vivo under pentobarbital anesthesia was observed in both kitW/ kitW-vand +/+ mice after exposure to O3. Thus, although mast cells are activated in vivo by O3and participate in O3-induced polymorphonuclear cell infiltration into the pulmonary parenchyma, they do not participate detectably in the development of O3-induced airway hyperresponsiveness in mice.
Rate of nitric oxide production by lower alveolar airways of human lungs
Authors: Geigel Edgar J. , Hyde Richard W. , Perillo Irene B. , Torres Alfonso , Perkins Peter T. , Pietropaoli Anthony P. , Frasier Lauren M. , Frampton Mark W. , Utell Mark J.
Published: December 2017

This report describes methods for measuring nitric oxide production by the lungs’ lower alveolar airways (V˙no), defined as those alveoli and bronchioles well perfused by the pulmonary circulation. Breath holding or vigorous rebreathing for 15–20 s minimizes removal of NO from the lower airways and results in a constant partial pressure of NO in the lower airways (Pl). Then the amount of NO diffusing into the perfusing blood will be the pulmonary diffusing capacity for NO (Dno) multiplied by Pl and by mass balance equalsV˙no, or V˙no = Dno(Pl). To measure Pl, 10 normal subjects breath held for 20 s followed by exhalation at a constant flow rate of 0.83 ± 0.14 (SD) l/s or rebreathed at 59 ± 15 l/min for 20 s while NO was continuously measured at the mouth. Dno was estimated to equal five times the single-breath carbon monoxide diffusing capacity. By using breath holding, Pl equaled 2.9 ± 0.8 mmHg × 10−6and V˙noequaled 0.39 ± 0.12 μl/min. During rebreathing Pl equaled 2.3 ± 0.6 mmHg × 10−6andV˙no equaled 0.29 ± 0.11 μl/min. Measurements of NO at the mouth during rapid, constant exhalation after breath holding for 20 s or during rebreathing provide reproducible methods for measuringV˙no in humans.
Prolonged hypoxia increases vascular endothelial growth factor mRNA and protein in adult mouse brain
Authors: Kuo Ning-Tsu , Benhayon David , Przybylski Ronald J. , Martin Richard J. , LaManna Joseph C.
Published: December 2017

Brain hypoxia induces an increase in brain vascularity, presumably mediated by vascular endothelial growth factor (VEGF), but it is unclear whether VEGF is required to maintain the increase. In these studies, brain VEGF mRNA and protein levels were measured in adult mice kept in hypobaric chambers at 0.5 atm for 0, 0.5, 1, 2, 4, 7, and 21 days. Hypoxia was accompanied by a transient increase of VEGF mRNA expression: twofold by 0.5 day and a maximum of fivefold by 2 days; these were followed by a decrease at 4 days and a return to basal levels by 7–21 days. VEGF protein expression induced by hypoxia was bimodal, initially paralleling VEGF mRNA. There was an initial small increase at 12 h that reached a maximum by day 2, and, after a transient decrease on day 4, the protein expression increased again on day 7 before it returned to normoxic levels after 21 days. Thus, despite continued hypoxia, both VEGF mRNA and protein levels returned to basal after 7 days. These data suggest a metabolic negative-feedback system for VEGF expression during prolonged hypoxia in the brain.
Comparison of leucine kinetics in endurance-trained and sedentary humans
Authors: Lamont Linda S. , McCullough Arthur J. , Kalhan Satish C.
Published: December 2017

Whole body leucine kinetics was compared in endurance-trained athletes and sedentary controls matched for age, gender, and body weight. Kinetic studies were performed during 3 h of rest, 1 h of exercise (50% maximal oxygen consumption), and 2 h of recovery. When leucine kinetics were expressed both per unit of body weight and per unit of fat-free mass, both groups demonstrated an increase in leucine oxidation during exercise ( P < 0.01). Trained athletes had a greater leucine rate of appearance during exercise and recovery compared with their sedentary counterparts ( P < 0.05) and an increased leucine oxidation at all times on the basis of body weight ( P < 0.05). However, all of these between-group differences were eliminated when leucine kinetics were corrected for fat-free tissue mass. Therefore, correction of leucine kinetics for fat-free mass may be important when cross-sectional investigations on humans are performed. Furthermore, leucine oxidation, when expressed relative to whole-body oxygen consumption during exercise, was similar between groups. It is concluded that there was no difference between endurance-trained and sedentary humans in whole body leucine kinetics during rest, exercise, or recovery when expressed per unit of fat-free tissue mass.
Changes in satellite cell content and myosin isoforms in low-frequency-stimulated fast muscle of hypothyroid rat
Authors: Putman Charles T. , Düsterhöft Sabine , Pette Dirk
Published: December 2017

Chronic low-frequency stimulation was used to study the effects of enhanced contractile activity on satellite cell content and myosin isoform expression in extensor digitorum longus muscles from hypothyroid rats. As verified by immunohistochemical staining for desmin, vimentin, and myosin heavy chain (MHC) isoforms and by histological analysis, stimulation induced a transformation of existing fast fibers toward slower fibers without signs of fiber deterioration or regeneration. Immunohistochemically detected increases in MHC I and MHC IIa isoforms, as well as reduced numbers of fibers expressing the faster MHC isoforms, mirrored the rearrangement of the thick-filament composition. These changes, especially the upregulation of MHC IIa, were accompanied by an induction of developmental MHC isoforms in the transforming adult fibers. Satellite cell content rose 2.6-, 3.0-, and 3.7-fold over that of corresponding controls ( P < 0.05 in all cases) in 5-, 10-, and 20-day-stimulated muscles, respectively. Hypothyroidism alone had no effect on satellite cell content but resulted in a significant reduction in fiber size. The relative satellite cell contents increased ( P< 0.05) from 3.8% in euthyroid control muscles to 7.9, 11.5, and 13.8% in the 5-, 10-, and 20-day-stimulated hypothyroid muscles, respectively. In 20-day-stimulated muscles, the relative satellite cell content reached an almost twofold higher level than that of normal slow-twitch soleus muscle. This increase occurred concomitantly with a rise in myonuclear density, most probably because of the fusion of satellite cells with existing fibers.
Effects of load and tone on the mechanics of isolated human bronchial smooth muscle
Authors: Blanc François-Xavier , Salmeron Sergio , Coirault Catherine , Bard Martin , Fadel Elie , Dulmet Elisabeth , Dartevelle Philippe , Lecarpentier Yves
Published: December 2017

Isotonic and isometric properties of nine human bronchial smooth muscles were studied under various loading and tone conditions. Freshly dissected bronchial strips were electrically stimulated successively at baseline, after precontraction with 10−7 M methacholine (MCh), and after relaxation with 10−5 M albuterol (Alb). Resting tension, i.e., preload determining optimal initial length ( L o) at baseline, was held constant. Compared with baseline, MCh decreased muscle length to 93 ± 1% L o( P < 0.001) before any electrical stimulation, whereas Alb increased it to 111 ± 3% L o( P < 0.01). MCh significantly decreased maximum unloaded shortening velocity (0.045 ± 0.007 vs. 0.059 ± 0.007 L o/s), maximal extent of muscle shortening (8.4 ± 1.2 vs. 13.9 ± 2.4% L o), and peak isometric tension (6.1 ± 0.8 vs. 7.2 ± 1.0 mN/mm2). Alb restored all these contractile indexes to baseline values. These findings suggest that MCh reversibly increased the number of active actomyosin cross bridges under resting conditions, limiting further muscle shortening and active tension development. After the electrically induced contraction, muscles showed a transient phase of decrease in tension below preload. This decrease in tension was unaffected by afterload levels but was significantly increased by MCh and reduced by Alb. These findings suggest that the cross bridges activated before, but not during, the electrically elicited contraction may modulate the phase of decrease in tension below preload, reflecting the active part of resting tension.
Structure-function relationships in the pulmonary arterial tree
Authors: Dawson Christopher A. , Krenz Gary S. , Karau Kelly L. , Haworth Steven T. , Hanger Christopher C. , Linehan John H.
Published: December 2017

Knowledge of the relationship between structure and function of the normal pulmonary arterial tree is necessary for understanding normal pulmonary hemodynamics and the functional consequences of the vascular remodeling that accompanies pulmonary vascular diseases. In an effort to provide a means for relating the measurable vascular geometry and vessel mechanics data to the mean pressure-flow relationship and longitudinal pressure profile, we present a mathematical model of the pulmonary arterial tree. The model is based on the observation that the normal pulmonary arterial tree is a bifurcating tree in which the parent-to-daughter diameter ratios at a bifurcation and vessel distensibility are independent of vessel diameter, and although the actual arterial tree is quite heterogeneous, the diameter of each route, through which the blood flows, tapers from the arterial inlet to essentially the same terminal arteriolar diameter. In the model the average route is represented as a tapered tube through which the blood flow decreases with distance from the inlet because of the diversion of flow at the many bifurcations along the route. The taper and flow diversion are expressed in terms of morphometric parameters obtained using various methods for summarizing morphometric data. To help put the model parameter values in perspective, we applied one such method to morphometric data obtained from perfused dog lungs. Model simulations demonstrate the sensitivity of model pressure-flow relationships to variations in the morphometric parameters. Comparisons of simulations with experimental data also raise questions as to the “hemodynamically” appropriate ways to summarize morphometric data.
Effects of acetaminophen and ibuprofen on renal function in anesthetized normal and sodium-depleted dogs
Authors: Colletti Adria E. , Vogl Helen W. , Rahe Therese , Zambraski Edward J.
Published: December 2017

In certain conditions, renal prostaglandins (PGs) are important determinants of kidney function. Under these “renal PG-dependent states,” pharmacological inhibition of vasodilatory PG may result in excessive renal vasoconstriction and adversely affect kidney function. The purposes of this study were to determine whether acetaminophen (Acet), a weak PG-synthesis inhibitor, influences kidney function in the renal PG-dependent state of anesthesia and sodium depletion. Comparisons were made with ibuprofen (Ibu). Measurements of PGE2excretion were used to assess renal PG synthesis. Acet (15 mg/kg) and Ibu (10 mg/kg) both decreased renal blood flow and glomerular filtration rate by ∼20–30% in normal, anesthetized, sodium-replete dogs. Although Acet produced similar changes in renal blood flow and glomerular filtration rate in the low-sodium dogs, Ibu caused a significantly greater renal vasoconstriction (64 ± 10%) in these animals. Both Acet and Ibu inhibited urinary PGE2excretion in sodium-replete and low-sodium dogs. Ibu tended to have a greater and more prolonged effect than did Acet. These results suggest that Acet alters PGE2excretion and kidney function under renal PG-dependent conditions; the effects, however, are less severe than those seen with Ibu.
Gravity is an important but secondary determinant of regional pulmonary blood flow in upright primates
Authors: Glenny Robb W. , Bernard Susan , Robertson H. Thomas , Hlastala Michael P.
Published: December 2017

Original studies leading to the gravitational model of pulmonary blood flow and contemporary studies showing gravity-independent perfusion differ in the recent use of laboratory animals instead of humans. We explored the distribution of pulmonary blood flow in baboons because their anatomy, serial distribution of vascular resistances, and hemodynamic responses to hypoxia are similar to those of humans. Four baboons were anesthetized with ketamine, intubated, and mechanically ventilated. Different colors of fluorescent microspheres were given intravenously while the animals were in the supine, prone, upright (repeated), and head-down (repeated) postures. The animals were killed, and their lungs were excised, dried, and diced into ∼2-cm3 pieces with the spatial coordinates recorded for each piece. Regional blood flow was determined for each posture from the fluorescent signals of each piece. Perfusion heterogeneity was greatest in the upright posture and least when prone. Using multiple-stepwise regression, we estimate that 7, 5, and 25% of perfusion heterogeneity is due to gravity in the supine, prone, and upright postures, respectively. Although important, gravity is not the predominant determinant of pulmonary perfusion heterogeneity in upright primates. Because of anatomic similarities, the same may be true for humans.
Experimental neonatal respiratory failure induced by lysophosphatidylcholine: effect of surfactant treatment
Authors: Grossmann Gertie , Tashiro Katsumi , Kobayashi Tsutomu , Suzuki Yasuhiro , Matsumoto Yutaka , Waseda Yuko , Akino Toyoaki , Curstedt Tore , Robertson Bengt
Published: December 2017

The purpose of this study was to characterize the toxic effects of lysophosphatidylcholine (lyso-PC) on neonatal lung function. Various doses of lyso-PC (from 0 to 40 mg/kg) were administered to near-term newborn rabbits. Lung-thorax compliance during mechanical ventilation was significantly decreased by doses ≥10 mg/kg, and static lung volumes during deflation were decreased by doses ≥20 mg/kg. Using the same experimental model, we investigated the effects of modified porcine surfactant (Curosurf, 200 mg/kg). Animals exposed to lyso-PC at birth and treated simultaneously with surfactant showed a satisfactory therapeutic response, whereas those treated after 30 min failed to respond. These animals also had a much larger leak of albumin into the air spaces and an elevated minimum surface tension of the lavage fluid in a pulsating bubble surfactometer, suggesting inactivation of the exogenous surfactant. Timing of surfactant administration may thus be essential for the therapeutic effect in this experimental model of acute lung injury.
Diaphragmatic lipid peroxidation in chronically loaded rats
Authors: Supinski G. , Nethery D. , Stofan D. , Hirschfield W. , DiMarco A.
Published: December 2017

Recent work indicates that free radical-mediated lipid peroxidation takes place within the diaphragm on strenuous contraction. This phenomenon has only been demonstrated using fairly artificial experimental models and has not been studied during the type of sustained respiratory loading typically seen in patients with lung disease. The purpose of the present study was to measure the levels of several biochemical markers of protein oxidation (protein carbonyl levels) and lipid peroxidation (8-isoprostane, reduced glutathione, and oxidized glutathione levels) in diaphragms of rats subjected to chronic respiratory loading. Respiratory loading was accomplished by tracheal banding; groups of animals were loaded for 4, 8, or 12 days, and a group of sham-operated unloaded animals was used as controls. After loading, animals were killed, diaphragm contractility was assessed in vitro by using a portion of the excised diaphragm, and the remaining diaphragm and the soleus muscles were used for biochemical analysis. We found diminished force generation in diaphragms from all groups of banded animals compared with muscles from controls. For example, twitch force averaged 7.8 ± 0.8 (SE) N/cm2 in unloaded animals and 4.0 ± 0.4, 3.0 ± 0.4, and 3.4 ± 0.4 N/cm2 in animals loaded for 4, 8, and 12 days, respectively ( P < 0.0001). Loading also elicited increases in diaphragmatic protein carbonyl concentrations ( P < 0.001), and the time course of alterations in carbonyl levels paralleled loading-induced alterations in the diaphragm force-frequency relationship. Although loading was also associated with increases in diaphragmatic 8-isoprostane levels ( P< 0.003) and reductions in diaphragm reduced glutathione levels ( P < 0.003), the time course of changes in these latter parameters did not correspond to alterations in force. Soleus glutathione and carbonyl levels were not altered by banding. We speculate that respiratory loading-induced alterations in diaphragmatic force generation may be related to free radical-mediated protein oxidation, but not to free radical-induced lipid peroxidation.
Comparison of femoral blood gases and muscle near-infrared spectroscopy at exercise onset in humans
Authors: MacDonald Maureen J. , Tarnopolsky Mark A. , Green Howard J. , Hughson Richard L.
Published: December 2017

We hypothesized that near-infrared spectroscopy (NIRS) measures of hemoglobin and/or myoglobin O2 saturation (IR-So 2) in the vascular bed of exercising muscle would parallel changes in femoral venous O2 saturation (S[Formula: see text]) at the onset of leg-kicking exercise in humans. Six healthy subjects performed transitions from rest to 48 ± 3 (SE)-W two-legged kicking exercise while breathing 14, 21, or 70% inspired O2. IR-So 2 was measured over the vastus lateralis muscle continuously during all tests, and femoral venous and radial artery blood samples were drawn simultaneously during rest and during 5 min of exercise. In all gas-breathing conditions, there was a rapid decrease in both IR-So 2 and SfvO2 at the onset of moderate-intensity leg-kicking exercise. Although SfvO2 remained at low levels throughout exercise, IR-So 2increased significantly after the first minute of exercise in both normoxia and hyperoxia. Contrary to the hypothesis, these data show that NIRS does not provide a reliable estimate of hemoglobin and/or O2 saturation as reflected by direct femoral vein sampling.
Aerosol probes of lung injury in a 28-wk longitudinal study of mild experimental emphysema in dogs
Authors: Rosenthal Frank S.
Published: December 2017

After baseline measurements of lung mechanics, effective air space diameter (EAD), and aerosol dispersion (AD), three dogs were exposed to two treatments of aerosolized papain (3 ml of a 4% solution), and measurements were repeated during a 28-wk follow-up period. EAD and AD were measured with boluses of 0.7-μm particles of di-2-ethylhexl sebacate, with Pen (i.e., volumetric bolus penetration/total lung capacity) between 0.1 and 0.4. After papain exposure, EAD increased a mean of 28% ( P < 0.0001) and AD (Pen = 0.3, 0.4) increased 4–7% ( P < 0.03). The progression of injury was indicated by increasing trends in total lung capacity ( P < 0.05), residual volume ( P < 0.05), and EAD ( P = 0.06) through week 18. There was no evidence of disease progression between weeks 18and 28, whereas some of the data for individual dogs suggested partial recovery from lung injury at week 28. The results show that aerosol probes can detect and characterize mild lung injury in experimental emphysema.
Exercise-induced alterations in skeletal muscle myosin heavy chain phenotype: dose-response relationship
Authors: Demirel Haydar A. , Powers Scott K. , Naito Hisashi , Hughes Michael , Coombes Jeff S.
Published: December 2017

This study investigated the effects of exercise training duration on the myosin heavy chain (MHC) isoform distribution in rat locomotor muscles. Female Sprague-Dawley rats (120 days old) were assigned to either a sedentary control group or to one of three endurance exercise training groups. Trained animals ran on a treadmill at ∼75% maximal O2uptake for 10 wk (4–5 days/wk) at one of three different exercise durations (30, 60, or 90 min/day). Training resulted in increases ( P < 0.05) in citrate synthase activity in the soleus and extensor digitorum longus in both the 60 and 90 min/day duration groups and in the plantaris (Pla) in all three exercise groups. All durations of training resulted in a reduction ( P < 0.05) in the percentage of MHCIIband an increase ( P < 0.05) in the percentage of MHCIIain the Pla. The magnitude of change in the percentage of MHCIIbin the Pla increased as a function of the training duration. In the extensor digitorum longus, 90 min of daily exercise promoted a decrease ( P < 0.05) in percentage of MHCIIband increases ( P < 0.05) in the percentages of MHCI, MHCIIa, and MHCIId/x. Finally, training durations ≥60 min resulted in an increase ( P < 0.05) in the percentage of MHCIand a concomitant decrease ( P < 0.05) in the percentage of MHCIIain the soleus. These results demonstrate that increasing the training duration elevates the magnitude of the fast-to-slow shift in MHC phenotype in rat hindlimb muscles.