bluuebunny/crossref_metadata_2025 huggingface dataset:
Predominant role of peripheral chemoreceptors in the termination of apnea in maturing newborn lambs
Authors: Delacourt C. , Canet E. , Bureau M. A.
Published: December 2017

Apneas are very common and normal in newborns but may become life threatening if they are not terminated appropriately. The aim of this study in newborn lambs was to investigate the influence on apnea termination of postnatal maturation, peripheral chemoreceptor function, and hypoxia. Apneas were induced by passive hyperventilation at varying inspired O2 fraction levels. The apnea termination threshold PCO2 (PATTCO2) was defined as the arterial PCO2 value at the first breath after the apnea. Three groups of awake intubated lambs were studied: 1) intact lambs tested at both 1 and 15 days of life, 2) intact 1-day-old lambs with central tissue hypoxia induced by CO inhalation, and 3) 1-day-old lambs with carotid body denervation (CBD). In individual lambs and regardless of age and carotid body function, there was a PO2-PCO2 response curve that was a determinant for the termination of an apnea. PATTCO2 invariably increased when arterial PO2 increased, regardless of age. During hypoxia and normoxia, PATTCO2 was significantly lower in 15-day-old lambs compared with 1-day-old lambs. No difference was seen during hyperoxia. PATTCO2 values were shifted to higher levels after carotid body removal. Finally, hypoxia induced by either a low inspired O2 fraction or CO inhalation consistently failed to induce a depressive effect on the PATTCO2 even in CBD lambs. In conclusion, in awake newborn lambs, the PCO2 level for apnea termination changed with postnatal age, and carotid body function was essential in lowering PATTCO2, thus protecting the lambs against prolonged apnea. Furthermore, hypoxia consistently failed to depress the reinitiation of breathing after apnea, even in CBD lambs.
Acute effects of caffeine ingestion at rest in humans with impaired epinephrine responses
Authors: Van Soeren M. , Mohr T. , Kjaer M. , Graham T. E.
Published: December 2017

Caffeine ingestion has been demonstrated to increase circulating epinephrine (Epi) and norepinephrine (NE), elevate free fatty acids (FFAs), and alter heart rate, blood pressure (BP), and ventilation in humans. Whether these physiological responses are a result of caffeine acting through direct stimulation of specific tissues via adenosine receptors or secondary to Epi increases is not known. In the present experiment, six tetraplegics (level of spinal cord lesions C4-C6) were tested at rest for 3 h to investigate the effects of 6 mg/kg caffeine in capsule form on subjects with impaired Epi responses. Ventilatory, cardiovascular, metabolic, and hormonal data were collected every 15-20 min after caffeine ingestion. There were no significant (P > 0.05) increases in plasma Epi after caffeine ingestion [0.19 +/- 0.04 (SE) nM (preingestion); 0.20 +/- 0.04 nM (80 min postingestion)] or in plasma NE [0.53 +/- 0.16 nM (preingestion); 0.49 +/- 0.09 nM (80 min postingestion; P > 0.05)]. However, significant increases were found in serum FFAs [0.53 +/- 0.08 nM (preingestion); 1.03 +/- 0.20 mM (40 min postingestion; P < 0.05] and in glycerol. These concentrations remained elevated throughout the experiment. BP increased in the first hour postingestion. These data demonstrate that caffeine in physiological doses directly stimulates specific tissues, i.e., adipose and peripheral vascular tissue, and these effects are not secondary to increases in Epi after caffeine ingestion.
Women have lower tolerance to lower body negative pressure than men
Authors: White D. D. , Gotshall R. W. , Tucker A.
Published: December 2017

Studies of the cardiovascular response to lower body negative pressure (LBNP) in men and women have suggested that women may have less tolerance to LBNP than men, although tolerance per se was not determined. To investigate the effect of gender on tolerance to LBNP, 10 men 10 women were subjected to increasing levels of LBNP until presyncopal symptoms developed. The cumulative stress index (CSI) score was determined, as were cardiovascular variables. Women had 62% less tolerance to LBNP with a CSI of 412 +/- 43 mmHg/min compared with a CSI of 1,070 +/- 149 mmHg/min for men. Cardiovascular changes associated with LBNP were similar for men and women when expressed relative to the occurrence of presyncope, but women had a higher heart rate response when the data were expressed at absolute levels of LBNP (-30 and -50 mmHg LBNP). Thus men and women had similar cardiovascular adjustments to the LBNP, with the changes in women occurring lower levels of LBNP. These data are important in a consideration of the development of antigravitational countermeasures for women. These data raise questions as to the manner in which blood pools within the lower body in men and women under LBNP.
Lung water is increased in regions of higher neutrophil retention after acute bead embolization
Authors: Tsang J. , Brush B.
Published: December 2017

Previous reports have shown that neutrophils are retained in the lung after acute embolization and that these neutrophils play an important role in the subsequent formation of permeability pulmonary edema. The present study was designed to test the hypothesis that acute embolic injury results in microvascular damage in lung regions with the greater retention of neutrophils. Seventeen pigs (20 +/- 2 kg) were embolized by injecting polystyrene beads (250 microns; labeled with 131I) into the right atrium over 5 min. Five pigs, which received no embolic beads, served as controls. Neutrophils (89 +/- 5% pure), isolated on Ficoll-Histopaque gradient, were radiolabeled with 111In-oxine. Twenty minutes after embolization, the radiolabeled neutrophils were injected into the right atrium along with 85Sr-labeled microspheres to mark the initial neutrophil distribution within the lung as well as the regional pulmonary blood flow at the time of their delivery. The animals were killed 50 min after embolization, and the lungs were removed, frozen over liquid nitrogen, and cut into 60 samples. The data show that after embolization regional neutrophil retention was inversely related to the regional blood flow but was not affected by the embolic load in the same region. Regional extravascular lung water was increased in regions of higher neutrophil retention, but the regions with increased edema did not receive a greater embolic load. These results show that microvascular injury occurs in the lung regions with the greatest neutrophil retention and that this increased retention of neutrophils is unrelated to the extent of embolization.
Decreased Ca2+ sensitivity of isometric tension in skinned cardiac myocytes from tail-suspended rats
Authors: Dunlap A. W. , Thomason D. B. , Menon V. , Hofmann P. A.
Published: December 2017

Tail suspension in rats causes a cephalic shift in blood, resulting in a volume load on the heart similar to that observed during microgravity spaceflight or mild heart failure. The present study determined the influence of increased cardiac hemodynamic load on myofilament isometric tension as a function of Ca2+ concentration in skinned cardiac myocytes of control and 7-day head-down tilt Sprague-Dawley rats. Isometric force of single skinned myocytes was measured by attaching cells with adhesive to a force transducer and piezoelectric translator. A significant decrease in the Ca2+ sensitivity of tension was observed in cardiac myocytes from suspended rats [pCa of half-maximal tension (pCa50) of 5.83 +/- 0.03] compared with control rats (pCa50 of 5.94 +/- 0.03). Maximum tension generation and slope of the tension-pCa relationship were unaffected by head-down tilt. Electrophoretic analysis of myofilament proteins indicates differences in expression of proteins in the 50-60 and 100-120 kDa ranges; immunoblot analysis of tubulin (50 kDa) expression indicates no change in the ratio of beta-tubulin to light chain 1 or tropomyosin. Decreased force-producing ability at a given submaximum Ca2+ concentration in cardiac myocytes from suspended rats suggests a decrease in contractility possibly due to changes in cardiac myofilament protein expression following chronic elevated volume load on the heart.
Neurocirculatory consequences of abrupt change in sleep state in humans
Authors: Morgan B. J. , Crabtree D. C. , Puleo D. S. , Badr M. S. , Toiber F. , Skatrud J. B.
Published: December 2017

The arterial pressure elevations that accompany sleep apneas may be caused by chemoreflex stimulation, negative intrathoracic pressure, and/or arousal. To assess the neurocirculatory effects of arousal alone, we applied graded auditory stimuli during non-rapid-eye-movement (NREM) sleep in eight healthy humans. We measured muscle sympathetic nerve activity (intraneural microelectrodes), electroencephalogram (EEG; C4/A1 and O1/A2), arterial pressure (photoelectric plethysmography), heart rate (electrocardiogram), and stroke volume (impedance cardiography). Auditory stimuli caused abrupt increases in systolic and diastolic pressures (21 +/- 2 and 15 +/- 1 mmHg) and heart rate (11 +/- 2 beats/min). Cardiac output decreased (-10%). Stimuli that produced EEG evidence of arousal evoked one to two large bursts of sympathetic activity (316 +/- 46% of baseline amplitude). Stimuli that did not alter EEG frequency produced smaller but consistent pressor responses even though no sympathetic activation was observed. We conclude that arousal from NREM sleep evokes a pressor response caused by increased peripheral vascular resistance. Increased sympathetic outflow to skeletal muscle may contribute to, but is not required for, this vasoconstriction. The neurocirculatory effects of arousal may augment those caused by asphyxia during episodes of sleep-disordered breathing.
Cardiovascular and ventilatory response to isocapnic hypoxia at sea level and at 5,050 m
Authors: Insalaco G. , Romano S. , Salvaggio A. , Braghiroli A. , Lanfranchi P. , Patruno V. , Donner C. F. , Bonsignore G.
Published: December 2017

To assess the effect of chronic hypoxic conditions on ventilatory, heart rate (HR), and blood pressure (BP) responses to acute progressive isocapnic hypoxia, we studied five healthy Caucasian subjects (3 men and 2 women). Each subject performed one rebreathing test at sea level (SL) and two tests at the Pyramid laboratory at Lobuche, Nepal, at the altitude of 5,050 m, 1 day after arrival (HA1) and after 24 days of sojourn (HA2). The effects of progressive isocapnic hypoxia were tested by using a standard rebreathing technique. BP, electrocardiogram, arterial oxygen saturation, airflow and end-tidal CO2 and O2 were recorded. For each subject, the relationships between arterial oxygen saturation and HR, systolic BP and minute ventilation (VE), respectively, were evaluated. At HA1, the majority of subjects showed a significant increase in VE and BP response and a decrease in HR response to progressive isocapnic hypoxia as compared to SL. At HA2, VE and BP responses further increased, whereas the HR response remained similar to that observed at HA1. A significant relationship between hypoxic ventilatory responses and both systolic and diastolic BP responses to progressive hypoxia was found. No significant correlation was found between hypoxic ventilatory and HR responses.
Effects of exogenous surfactant on lung pressure-volume characteristics during liquid ventilation
Authors: Tarczy-Hornoch P. , Hildebrandt J. , Mates E. A. , Standaert T. A. , Lamm W. J. , Hodson W. A. , Jackson J. C.
Published: December 2017

Total liquid ventilation (LV) lowers airway pressures and potentially reduces barotrauma in models of hyaline membrane disease. LV eliminates surface tension by eliminating the air-perfluorochemicals (PFC) interface but does not eliminate interfacial tension (IT) at the lung/PFC interface. We hypothesized that pretreatment with exogenous surfactant before LV would shift the overall pressure-volume (PV) curve to the left, compared with LV without surfactant. Sequential quasi-static PV curves were obtained in 10 excised lungs (saline, air, PFC), with one-half randomized to exogenous surfactant replacement before LV. Analysis revealed that maximal inflation pressures were reduced during LV compared with baseline air curves. Addition of exogenous surfactant to LV further reduced maximal inflation pressures. A novel approach was used to transform these PV curves to estimates of in situ IT-volume curves. Estimated maximal IT at 20 ml/kg in preterm lamb lungs on air inflation after surfactant was 51 mN/m, compared with 40 mN/m for LV alone and with 27 mN/m for the combination of surfactant and LV. We conclude that the IT-reducing properties of the PFC studied (perflubron) can be augmented through the use of exogenous surfactant.
Use of a hypoxic lung as a deoxygenator to provide extended assessment of pulmonary function in rats
Authors: DeCampos K. N. , Keshavjee S. H. , Tremblay L. , Yamashiro T. , Slutsky A. S.
Published: December 2017

Isolated perfused lung systems are commonly used to assess lung function in experimental studies. Assessment of hemodynamics and gas-exchange function in these systems is limited by the availability of venous blood. This study describes and validates a rat lung perfusion circuit in which a double-lung block ventilated with a hypoxic gas mixture [inspired O2 fraction (FIO2) 0.04; inspired CO2 fraction 0.08; deoxygenator (Deoxy) block] is used to provide blood with blood gases that are similar to mixed venous values to perfuse a study lung (FIO2 0.21; left lung only). This allows extended assessment of hemodynamics and gas exchange. Fifty adult male Wistar rats (300-400 g) were used as double-lung donors. Twenty-five perfusions (of both Deoxy and study lungs) were performed in four protocols (groups 1-5; n = 5). In protocol 1 (group 1), we tested whether exposure to room air affects the gas composition of the blood in the system. We found that the gas composition of the venous reservoir blood was identical to that of the blood entering the study block. In protocol 2, the effect of perfusion time and perfusion flow rate on the stability of the system was assessed. Lungs were perfused at 4 and 12 ml/min (groups 2 and 3, respectively), and the procedure was discontinued if edema or a marked decline in hemodynamics or gas-exchange function was observed. Pulmonary function was excellent and remained stable for 3 (at 12 ml/min) and 5 h (at 4 ml/min). In protocol 3, we examined whether hypoxic ventilation in the Deoxy lungs affects the stability of the system. Despite the low FIO2 used in the Deoxy lungs, the mean pulmonary arterial pressure-to-blood flow relationships in the study and Deoxy lungs were similar. Finally, in protocol 4, perfusion of a damaged study lung did not impair the function of the system. We conclude that this model permits reliable assessment of pulmonary function in rats under controlled ventilation and perfusion conditions. The use of a Deoxy double-lung block simplifies the perfusion apparatus and eliminates the main cause of instability of other systems that use an anesthetized host animal to provide venous blood.
Microgravity-induced transformations of myosin isoforms and contractile properties of skeletal muscle
Authors: Caiozzo V. J. , Haddad F. , Baker M. J. , Herrick R. E. , Prietto N. , Baldwin K. M.
Published: December 2017

This study examined the effects of microgravity (14 days) on 1) the contractile properties of the soleus (Sol), an antigravity skeletal muscle; and 2) the myosin heavy chain (MHC) protein and mRNA isoform content of the Sol, vastus intermedius (VI), plantaris (Plan), and tibialis anterior (TA) muscles. The force-velocity relationships of the flight Sol muscles had a significant reduction in maximal isometric tension (-37%) and a corresponding increase in maximal shortening velocity (+20%). Additionally, the force-frequency relationship of the flight Sol muscles was shifted to the right of the ground-based control group. Microgravity had the greatest effect on muscle fiber composition in the Sol muscle, with a reduction in slow muscle fibers and a corresponding increase in muscle fibers categorized as hybrid fibers. The estimated absolute MHC isoform content was altered to the greatest extent in the Sol and VI muscles, with significant decreases and elevations in the slow type I and fast type IIX MHC protein isoforms, respectively. Consistent with the protein data, both the flight Sol and VI muscles exhibited significant elevations in the fast type IIX MHC mRNA isoform. In contrast, however, the flight Plan and TA groups had significant increases in the fast type IIB MHC mRNA isoform content without corresponding changes at the protein level. The results of this study suggest that spaceflight of even short duration produces important changes in the contractile properties of antigravity skeletal muscle. These changes are mediated by alterations in MHC phenotype and reductions in muscle mass. In some instances, the alterations in MHC mRNA isoform content seemed to be uncoupled from those occurring at the protein level. This apparent uncoupling between mRNA and protein expression demonstrates that the effects of microgravity must be better understood at the transcriptional, translational, and post-translational levels.
Vertebral growth disturbance in rapidly growing rats during 14 days of spaceflight
Authors: Kitajima I. , Semba I. , Noikura T. , Kawano K. , Iwashita Y. , Takasaki I. , Maruyama I. , Arikawa H. , Inoue K. , Shinohara N. , Nagaoka S. , Ohira Y.
Published: December 2017

The effect of 14 days of spaceflight on the vertebrae of rapidly growing rats was studied. The hardness of the vertebrae was measured with a Knoop microhardness tester, and bone mineral density was measured from X-ray photographs. Histomorphometric examination was performed with a microcomputer-aided system. No significant difference (P > 0.05) was observed between flight rats and ground controls with regard to mechanical hardness or bone mineral density. However, histological examination revealed irregular thickening of the endosteal surface of cortical bone in the flight rats, whereas it was uniform in the ground controls. The relative area of lamellar bone showed a significant reduction (P < 0.001) in the flight rats. These findings suggest that the structural disturbances were due to retardation of endosteal modeling and remodeling. We conclude that delay of vertebral maturation can occur in rapidly growing rats after even short-term exposure to microgravity.
Effects of spaceflight and recovery on rat humeri and vertebrae: histological and cell culture studies
Authors: Zerath E. , Godet D. , Holy X. , Andre C. , Renault S. , Hott M. , Marie P. J.
Published: December 2017

Skeletal changes associated with spaceflight in the rat have been well documented, but few data are available on bone tissue and bone cell metabolism after subsequent on-Earth recovery. We therefore investigated the effects of microgravity and subsequent recovery on trabecular bone morphology and cellular activities in rat humeri and thoracic vertebrae and compared histomorphometric parameters in caudal vertebrae with the behavior of vertebral osteoblastic cells in culture. We report here that humeral weight showed normal growth during the experiment but was unaffected by spaceflight or recovery from spaceflight. However, the 14-day spaceflight resulted in inhibition of static indexes of bone formation in humeral proximal metaphyses and thoracic vertebral bodies. This was associated with a decrease in bone volume in humeral metaphyses. After 14 days of on-Earth recovery, osteoblastic and osteoid surfaces returned toward normal and bone volume was normalized in humeri, whereas the static bone formation parameters were not restored in thoracic vertebrae. In addition, histological indexes of bone formation and osteoblastic cell growth in vitro were not affected by spaceflight in caudal vertebrae. This study shows that rat humeri and thoracic and caudal vertebrae exhibit different patterns of response to spaceflight and subsequent on-Earth recovery, which could be due, at least in part, to the different loading pattern of these bones, and also to differences in bone turnover rate.
Effect of SLS-2 spaceflight on immunologic parameters of rats
Authors: Lesnyak A. , Sonnenfeld G. , Avery L. , Konstantinova I. , Rykova M. , Meshkov D. , Orlova T.
Published: December 2017

During the Spacelab Life Sciences-2 mission, rats were dissected in space and biosamples were returned to Earth for analysis. Immunologic studies addressed the kinetics of T lymphocyte proliferative responses, cytotoxic activity of natural killer cells, and cytokine production. Experiments were performed by using spleen and bone marrow of rats dissected before flight, during flight, immediately after landing of the space shuttle (R + 0), or 14 days after landing (R + 14), as well as those of respective control animals. Each group consisted of five male Sprague-Dawley rats. It was demonstrated that T lymphocyte activity of rats dissected in flight was significantly decreased compared with the controls. This was observed during 48-, 72-, and 96-h cultivation and stimulation with the following mitogenic stimuli: concanavalin A (Con A; 0.1, 1.0, and 10.0 mg/ml), phytohemagglutinin (PHA; 2.5 mg/ml), and interleukin-2 (IL-2; 1 U/ml). The cell proliferation rate in rats dissected immediately after landing did not decrease, whereas that in rats dissected at R + 14 increased. The activity of spleen natural killer cells was reduced in response to 51Cr-labeled target cells during flight (YAC-1 and K-562) and after flight (YAC-1). At R + 14, their activity returned to normal. Another technique employed to measure natural cytotoxicity, using [3H]uridine-labeled target cells and ribonuclease, did not reveal any differences between control and experimental groups. In bone marrow, the activity of natural killer cells did not vary significantly. The production of IL-1, IL-2, tumor necrosis factor (TNF)-alpha, and TNF-beta in spleen cell cultures of the flight rats was reduced. At R + 0, IL-1 and TNF-beta levels remained lowered, whereas TNF-alpha was increased. At R + 0, interferon-alpha and interferon-gamma levels were diminished. In summary, cell-mediated immunity in rats was significantly suppressed during flight. The time course variation of immune parameters after flight suggests that the changes may truly indicate a response of the immune system to spaceflight conditions that could increase over time.
Cellular content of p53 protein in rat skin after exposure to the space environment
Authors: Ohnishi T. , Inoue N. , Matsumoto H. , Omatsu T. , Ohira Y. , Nagaoka S.
Published: December 2017

The effects of stress in space, microgravity and space radiation, on living organisms are still unknown. We have examined the cellular content of p53 protein, a tumor-suppressor gene product, in skin from rats by the Western blot method using a blotting-amplification system. Three groups of rats were used. The first group was kept on Earth normally and showed hardly any detectable p53 protein. The second group made a 14-day flight into space on the second Spacelab Life Sciences-2 mission (F). The last group was subjected to the same kinds of stress as the rats in the second group except for spaceflight (SC). The F and the SC rats were killed on day zero (F-0 and SC-0 groups) and day nine (F-9 and SC-9 groups) after return. F-0 rats showed marked accumulation of p53 protein, whereas SC-0 rats showed a slight decrease. F-9 and SC-9 rats showed almost the same amount of p53 protein, but F-9 rats showed a slightly higher expression. From these results, it is suggested that the accumulation of cellular p53 protein is induced in rat skin cells by exposure to the space environment.
Central venous pressure in space
Authors: Buckey J. C. , Gaffney F. A. , Lane L. D. , Levine B. D. , Watenpaugh D. E. , Wright S. J. , Yancy C. W. , Meyer D. M. , Blomqvist C. G.
Published: December 2017

Gravity affects cardiac filling pressure and intravascular fluid distribution significantly. A major central fluid shift occurs when all hydrostatic gradients are abolished on entry into microgravity (microG). Understanding the dynamics of this shift requires continuous monitoring of cardiac filling pressure; central venous pressure (CVP) measurement is the only feasible means of accomplishing this. We directly measured CVP in three subjects: one aboard the Spacelab Life Sciences-1 space shuttle flight and two aboard the Spacelab Life Sciences-2 space shuttle flight. Continuous CVP measurements, with a 4-Fr catheter, began 4 h before launch and continued into microG. Mean CVP was 8.4 cmH2O seated before flight, 15.0 cmH2O in the supine legs-elevated posture in the shuttle, and 2.5 cmH2O after 10 min in microG. Although CVP decreased, the left ventricular end-diastolic dimension measured by echocardiography increased from a mean of 4.60 cm supine preflight to 4.97 cm within 48 h in microG. These data are consistent with increased cardiac filling early in microG despite a fall in CVP, suggesting that the relationship between CVP and actual transmural left ventricular filling pressure is altered in microG.
Regulation of lung expansion and lung growth before birth
Authors: Harding R. , Hooper S. B.
Published: December 2017

Fetal lung growth depends on the degree to which lungs are distended with luminal liquid. Fetal lungs are highly distended such that mean luminal volume exceeds the static relaxation volume. This high level of expansion is maintained by fetal breathing movements and by resistive effects of the upper airway during apnea; both factors oppose lung recoil. Mechanical stress in lung and other tissues stimulates cell division and tissue remodeling. Potential transduction mechanisms involve direct effects of cellular tension and mediation of locally released mitogenic factors. Further studies are required to further define links between lung tissue stress, increased growth, structural remodeling, and the endocrine environment. A common cause of fetal lung hypoplasia is a sustained reduction in mean lung expansion. Studies of mechanisms controlling fetal lung expansion have led to insights into the etiology of fetal lung hypoplasia and how it may be remedied in utero. Fetal lung hypoplasia can have long-lasting effects on postnatal lung function, as airway and alveolar formation may be compromised. Preterm birth may also result in incomplete structural development of the lungs as it shortens the period of increased intrauterine lung expansion.
Skeletal muscle mitochondria from AZT-treated rats have a diminished response to chronic electrical stimulation
Authors: McCurdy D. T. , Kennedy J. M.
Published: December 2017

Inhibition of DNA polymerase gamma-function mediated by 3'-azido-3'-deoxythymidine (AZT) has been proposed to cause a myopathy by reducing mitochondrial DNA (mtDNA) replication. Repeated bouts of exercise stimulate an increase in mtDNA replication, mitochondrial content, and mitochondrial volume fraction. Therefore, adaptation of rat skeletal muscle [tibialis anterior (TA)] mitochondria exposed to AZT (1 mg/ml for 35 days) and then to electrical stimulation for 8 h/day (7, 14, 21 days) with continued AZT treatment was examined. Fourteen and 21 days of stimulation increased TA cytochrome oxidase (CO) activity, mtDNA, and CO subunit III and VIc mRNA levels in both groups. The TA CO activity and CO III mRNA increases after 14 and 21 days of stimulation were diminished in AZT-treated rats. TA glyceraldehyde-3-phosphate dehydrogenase was reduced in normal rats after chronic stimulation but was unchanged in AZT-treated rats. Chronic stimulation increased the mitochondrial volume fraction by 80 and 40% in normal and AZT-treated rats, respectively. These results indicate diminution, but not complete inhibition, of mitochondrial adaptation by AZT-treated skeletal muscle in response to stimulation.
Angiogenic growth factor mRNA responses in muscle to a single bout of exercise
Authors: Breen E. C. , Johnson E. C. , Wagner H. , Tseng H. M. , Sung L. A. , Wagner P. D.
Published: December 2017

A major adaptation to exercise is new capillary formation in skeletal muscle. On the basis of angiogenesis in tumors and during development, several angiogenic growth factors may be involved, including vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and transforming growth factor-beta 1 (TGF-beta 1). In 9-wk-old female Wistar rats, mRNA expression for these three growth factors in gastrocnemius muscle was examined by quantitative Northern analysis after a single 1-h run at 15 or 20 m/min at 10 degrees incline in room air. A third group ran at 15 m/min in 12% O2, and resting control groups were included at inspired O2 fractions of 0.21 and 0.12. Exercise significantly increased mRNA levels two- to fourfold, which was evident over the first 4 h postexercise; by 8 and 24 h, mRNA levels returned to baseline. For all three factors, mRNA levels were significantly higher after exercise at 20 than at 15 m/min. Hypoxia at rest doubled VEGF and TGF-beta 1 message but had no effect on bFGF. Hypoxic exercise further raised VEGF mRNA levels but had no effect on the other factors. We suggest that VEGF, bFGF, and TGF-beta 1 may be involved in the angiogenic response to exercise and that reduced intracellular PO2 (as occurs during normoxic exercise) may be part of the stimulus to such growth factor production.
Force responses to constant-velocity shortening of electrically stimulated human muscle-tendon complex
Authors: Cook C. S. , McDonagh M. J.
Published: December 2017

Force-velocity curves in human muscle often have unexpectedly high forces at high velocities. If series elasticity is the cause, it should have less effect at lower activation levels and larger shortening amplitudes. The first dorsal interosseus muscle-tendon complex was shortened at different levels of activation and by different amplitudes. Force-velocity curves had high force well maintained at high velocities. With an actuator release of 4.21 mm at 80% of maximal activation, force was > 45% of isometric force (Po) for all actuator velocities > 200 mm/s (1.49 muscle lengths/s). At 30% activation, the force was > 25% of Po at these velocities. The smaller 2.46-mm releases produced higher forces than the 4.21-mm releases at these velocities. At 80% activation, force was > 65% of Po, and at 30% activation, it was > 50% of Po at these velocities. Corrections of these data for elasticity produced classic Hill-type force-velocity curves. A model incorporating the Hill force-velocity equation and a spring in series accounts for the results.
Blockade of glutamate receptors in CVLM and NTS attenuates airway dilation evoked from parabrachial region
Authors: Motekaitis A. M. , Solomon I. C. , Kaufman M. P.
Published: December 2017

Previous work from our laboratory has shown that stimulation of cell bodies and dendrites in the medial and lateral parabrachial nuclei dilates the airways. The sites participating in the pathway mediating this airway response are not known. Two likely candidates are the caudal ventrolateral medulla (CVLM) and the nucleus tractus solitarii (NTS). Using chloralose-anesthetized cats, we assessed the airway dilation evoked from the parabrachial region before and during bilateral blockade of the NTS or the CVLM. The airway dilation arising from stimulation of the parabrachial region was evoked by microinjection of DL-homocysteic acid (25 nl, 100 mM). Bilateral blockade of the NTS or CVLM, achieved by microinjection of kynurenic acid (50 nl, 100 mM), reversibly attenuated the airway dilation in every cat tested. On average, kynurenic acid-induced blockade of the NTS caused a more complete attenuation of the dilation evoked from the parabrachial region than did blockade of the CVLM. Bilateral microinjection of cobalt chloride (50 nl, 50 mM) into the CVLM gave inconclusive results, attenuating the airway dilation evoked from the parabrachial region in six cats and potentiating it in three others. We conclude that the CVLM and the NTS participate in the airway dilation arising from the parabrachial region.
Transient permeabilization of airway epithelium by mucosal water
Authors: Widdicombe J. H. , Azizi F. , Kang T. , Pittet J. F.
Published: December 2017

We describe a simple hyposmotic shock procedure whereby the apical membrane of airway epithelium can be made transiently leaky to proteins and other macromolecules. Bovine or human tracheal epithelial cells were grown as confluent polarized cell sheets on porous inserts. While physiological saline was maintained on the basolateral surface, the mucosal surface was exposed to water. This led to marked increases in the uptake of [14C]mannitol across both apical and basolateral membranes. On restoring saline to the mucosal surface, the [14C]mannitol permeability returned to preexposure levels with a half-life of approximately 5 min. Mucosal water also increased efflux of lactate dehydrogenase and the uptakes of fluorescent albumin and dextran (2,000 kDa). Water-induced increases in mannitol permeability were similar at 4 and 37 degrees C, suggesting that pinocytosis was not the mechanism. Detailed time courses of the uptake of dextran and the loss of lactate dehydrogenase and 36Cl showed that the bulk of the permeability increase occurred during the first 2- to 4-min exposure to water. Transepithelial resistance was reversibly decreased by exposure to water, but short-circuit current responses to transport blockers and secretagogues remained qualitatively normal. The hyposmotic shock procedure also successfully permeabilized apical membranes of primary cultures of nasal epithelial cells from a patient with cystic fibrosis (CF) and of JME/CF 15 cells, a cell line derived from CF bronchial epithelium. This simple and efficient procedure may prove useful in studies on the cell and molecular biology of airway and other epithelia.
Perceptual responses to linear acceleration after spaceflight: human neurovestibular studies on SLS-2
Authors: Merfeld D. M. , Polutchko K. A. , Schultz K.
Published: December 2017

Perceptual responses of four astronauts were measured before and after a 14-day Spacelab Life Sciences-2 mission during interaural (y-axis) and rostrocaudal (z-axis) linear acceleration to measure adaptive changes in perceptual responses to inertial cues. In one test, subjects used a joystick to null a pseudorandom velocity disturbance. Postflight, two of three subjects showed a significantly enhanced ability to null linear self-motion in the y-axis and z-axis orientations. In another test, the subjects used a joystick to indicate their direction of motion during a series of low-acceleration steps. The postflight responses of three of the four subjects showed a significant increase in the response latency for both y-axis and z-axis orientations. In a third test, subjects were asked to track a stationary but unseen target with their eyes while they translated linearly in the dark. No significant changes were observed in the postflight responses. The observed changes, when present, may be due to a reinterpretation of inertial cues that are functionally adaptive for the microgravity environment but are not optimal for responses on Earth.
Control of red blood cell mass in spaceflight
Authors: Alfrey C. P. , Udden M. M. , Leach-Huntoon C. , Driscoll T. , Pickett M. H.
Published: December 2017

The effect of spaceflight on red blood cell mass (RBCM), plasma volume (PV), erythron iron turnover, serum erythropoietin, and red blood cell (RBC) production and survival and indexes were determined for six astronauts on two shuttle missions, 9 and 14 days in duration, respectively. PV decreased within the first day. RBCM decreased because of destruction of RBCs either newly released or scheduled to be released from the bone marrow. Older RBCs survived normally. On return to Earth, plasma volume increased, hemoglobin concentration and RBC count declined, and serum erythropoietin increased. We propose that entry into microgravity results in acute plethora as a result of a decrease in vascular space. PV decreases, causing an increase in hemoglobin concentration that effects a decrease in erythropoietin or other growth factors or cytokines. The RBCM decreases by destruction of recently formed RBCs to a level appropriate for the microgravity environment. Return to Earth results sequentially in acute hypovolemia as vascular space dependent on gravity is refilled, an increase in plasma volume, a decrease in hemoglobin concentration (anemia), and an increase in serum erythropoietin.
Maximal exercise performance after adaptation to microgravity
Authors: Levine B. D. , Lane L. D. , Watenpaugh D. E. , Gaffney F. A. , Buckey J. C. , Blomqvist C. G.
Published: December 2017

The cardiovascular system appears to adapt well to microgravity but is compromised on reestablishment of gravitational forces leading to orthostatic intolerance and a reduction in work capacity. However, maximal systemic oxygen uptake (Vo2) and transport, which may be viewed as a measure of the functional integrity of the cardiovascular system and its regulatory mechanisms, has not been systematically measured in space or immediately after return to Earth after spaceflight. We studied six astronauts (4 men and 2 women, age 35–50 yr) before, during, and immediately after 9 or 14 days of microgravity on two Spacelab Life Sciences flights (SLS-1 and SLS-2). Peak Vo2 (Vo2peak) was measured with an incremental protocol on a cycle ergometer after prolonged submaximal exercise at 30 and 60% of Vo2peak. We measured gas fractions by mass spectrometer and ventilation via turbine flowmeter for the calculation of breath-by-breath Vo2, heart rate via electrocardiogram, and cardiac output (Qc) via carbon dioxide rebreathing. Peak power and Vo2 were well maintained during spaceflight and not significantly different compared with 2 wk preflight. Vo2peak was reduced by 22% immediately postflight (P < 0.05), entirely because of a decrease in peak stroke volume and Qc. Peak heart rate, blood pressure, and systemic arteriovenous oxygen difference were unchanged. We conclude that systemic Vo2peak is well maintained in the absence of gravity for 9–14 days but is significantly reduced immediately on return to Earth, most likely because of reduced intravascular blood volume, stroke volume, and Qc.
Bloodborne markers in humans during multiday exposure to ozone
Authors: Foster W. M. , Wills-Karp M. , Tankersley C. G. , Chen X. , Paquette N. C.
Published: December 2017

Intermittent exposure of the human lung to ambient levels of ozone (O3) was assayed in systemic fluids by using serum alpha-tocopherol (ST) as a gauge of oxidative stress and the blastogenic activity of peripheral blood monocytes as an index of immune function. Healthy men (n = 10) were evaluated over 3 consecutive days (130 min/day) of chamber exposure to O3 and filtered air (FA); subjects alternated between rest and light treadmill exercise during exposures. For O3, the level was varied at 20-min intervals, i.e., 250, 350, 450, 450, 350, and 250 parts/billion, and concluded with 10 min at 250 parts/billion. ST was quantitated by high-performance liquid chromatography techniques, and T-lymphocyte blastogenesis was measured in cell cultures of peripheral blood monocytes by comparing [3H]thymidine incorporation in mitogen-stimulated (concanavalin A) and nonstimulated cells. After the third day of O3 at 20 h postexposure, ST levels were reduced significantly compared with the FA control subjects (down 14%; -0.96 mumol/l). Mitogen-activated T lymphocytes exhibited a 61% increase in blastogenic activity after 3 days of O3 exposure, significant compared with the proliferative activity of activated T lymphocytes collected after FA or before O3. Acute airway function was impaired by O3, e.g., on day 1, the forced vital capacity and forced expiratory volume in 1 s were decreased 8% (-0.92 liter) and 14% (-0.86 l/s), respectively, from preexposure values, and full recovery was delayed beyond 24 h. Effects of O3 exposure on cellular and biochemical markers increased in magnitude after each exposure and did not parallel the apparent adaptability of bronchial sensitivity to O3.
Lung mechanics during induced bronchoconstriction
Authors: Pellegrino R. , Wilson O. , Jenouri G. , Rodarte J. R.
Published: December 2017

To elucidate differences in lung mechanics, we investigated the relative changes of partial forced expiratory flows at 50 and 30% of vital capacity, pulmonary resistance (RL), dynamic elastance (Edyn), and the effects of a deep inhalation (DI) on maximal flows, Edyn, and RL in eight asthmatic and eight normal individuals during bronchial challenges with methacholine, histamine, and ATP. RL was partitioned into inspiratory and expiratory resistance. Different constrictor agents did not induce specific patterns of response. For a given decrement of flow at 50 and 30% vital capacity, RL increased significantly more in normal than in asthmatic individuals. The ratio of inspiratory to expiratory RL was always < 1 at baseline but became > 1 in the majority of asthmatic and normal individuals when RL exceeded 12.2 +/- 0.9 cmH2O.1–1.s, suggesting that tidal inspiration may have induced transient bronchodilation in more constricted subjects. In asthmatic individuals, DI had a significantly smaller effect on flow but not on RL compared with normal individuals. The recovery of RL and Edyn after DI was faster than Edyn for both normal and asthmatic individuals. These findings are consistent with the idea that asthmatic individuals have a stronger peripheral response to agonists than normal individuals.
Development of hypoglossal motoneurons
Authors: Berger A. J. , Bayliss D. A. , Viana F.
Published: December 2017

Hypoglossal motoneurons (HMs) are brain stem motoneurons that innervate tongue muscles. Their function is critical in the control of the upper airway. Results from in vitro studies of rat HMs have shown that properties of HMs change during the postnatal period. For example, these studies have uncovered changes in HM morphology and electrical properties (both in ion channels and firing properties) as well as changes in chemical synaptic transmission to HMs during the postnatal period. Morphologically, a marked reduction in complexity of the dendritic tree takes place over the first 2 wk postnatal. In terms of electrical properties, a substantial and progressive fall in motoneuronal input resistance occurs during the first month of life, due to a decrease in specific membrane resistivity. This is primarily responsible for the progressive increase in rheobase and consequent reduction in cell excitability. In addition, the densities of at least two types of membrane ion channels are altered in early postnatal life, contributing to changes in their electroresponsive properties. On the one hand, the depolarizing mixed cationic current that is activated by membrane hyperpolarization was found to be approximately 10-fold larger in adult than in neonatal HMs. By contrast, neonatal HMs possess a transient low-voltage-activated T-type Ca2+ channel with a low single-channel conductance (approximately 7 pS), the density of which rapidly declines during the early postnatal period. The functional relevance of these and other changes occurring during the postnatal period is discussed.
Effects of salbutamol on rat diaphragm contractility
Authors: Van der Heijden H. F. , Van Balkom R. H. , Folgering H. T. , Van Herwaarden C. L. , Dekhuijzen P. N.
Published: December 2017

The aim of this study was to investigate 1) the effects and time course of single doses of salbutamol on isometric contractile properties of isolated rat diaphragm strips and 2) whether these effects were caused by a direct effect on the muscle. Two experiments were performed. In one, salbutamol was administered subcutaneously in doses of 12.5, 25, 50, or 100 micrograms/kg (25 and 50 micrograms/kg sc resulted in serum concentrations of approximately 9 and approximately 15 micrograms/l, respectively, 0.5 h after injection) and in vitro contractile properties were determined 0.5, 1, 2, or 4 h after administration; in the other, salbutamol was added to the tissue bath in a concentration of < or = 2, approximately 10, approximately 20, and approximately 80 micrograms/l. Twice force, maximal tetanic force, and twitch force-to-tetanic force ratio all increased in a dose-dependent way in both experiments. The increases in force generation were slightly higher after subcutaneous administration. Force-frequency curves were shifted upward in both experiments. No significant effects of time of salbutamol administration were found, but the increase in force generation was most pronounced within 2 h after subcutaneous administration. In conclusion, in vitro force generation can be improved by low concentrations of salbutamol. The slightly higher increases in force generation after subcutaneous administration suggest that in vivo salbutamol may have additional positive inotropic actions on diaphragm contractility besides a direct beta 2-adrenergic effect on the muscle itself.
Transmission of pressure within the abdomen
Authors: Tzelepis G. E. , Nasiff L. , McCool F. D. , Hammond J.
Published: December 2017

The extent to which transmission of pressure within the abdomen is accomplished in accordance with the laws of fluid mechanics, i.e., homogeneous transmission to all portions of the abdomen, is controversial. To examine the cranial-to-caudal as well as side-to-side transmission of pressure within the abdomen in humans, we measured intra-abdominal pressure at four sites in five subjects undergoing colonoscopy. Liquid-filled catheters were inserted into the colon, and intracolonic pressure was measured in the rectum and in transverse, descending, and sigmoid colon. Differences in intracolonic pressure were recorded during breaths to total lung capacity and brief expulsive maneuvers. Measurements were taken in the supine, right lateral, and seated position. Comparison of pressure swings at all sites showed that the pressure changes were nearly equal during both inspiratory and expulsive maneuvers. The changes in pressure were uniform in the cephalocaudal axis as from side to side. We conclude that transmission of abdominal pressure in humans is nearly homogeneous. Our findings provide support for the hydraulic model of abdominal mechanics.
Distal effects of tracheal gas insufflation: changes with catheter position and oleic acid lung injury
Authors: Nahum A. , Ravenscraft S. A. , Adams A. B. , Marini J. J.
Published: December 2017

We separated distal (turbulence-related) and proximal (dead space washout-related) effects of tracheal gas insufflation (TGI) by comparing the effects of straight and inverted catheters. We reasoned that the inverted catheter was unlikely to remove CO2 from conducting airways distal to its orifice. In six normal dogs during TGI at 10 l/min, advancing the catheters from 10 to 1 cm above the main carina decreased dead space volume by 29 +/- 12 and 12 +/- 6 ml (P < 0.04) with the straight and inverted catheters, respectively. By comparison, the tracheal volume between 10 and 1 cm above the carina was 15 +/- 2 ml. In another set of dogs (n = 5), we examined the distal effects of TGI before and after oleic acid-induced lung injury. During TGI at 10 l/min before and after oleic acid injury, the differences in arterial PCO2 between the straight and inverted catheters were 5 +/- and 9 +/- 6 Torr (P < 0.18), respectively. Our data suggest that distal effects of TGI become more pronounced as the catheter tip is positioned closer to the main carina. The distal effects of TGI were not diminished after oleic acid injury when minute ventilation was maintained constant.