bluuebunny/crossref_metadata_2025 huggingface dataset:
Brain stem Po2and pH of the working heart-brain stem preparation during vascular perfusion with aqueous medium
Authors: Wilson R. J. A. , Remmers J. E. , Paton J. F. R.
Published: December 2017

The rat working heart-brain stem preparation (WHBP) is an in situ preparation having many of the advantages associated with in vitro preparations while retaining cardiovascular response functionality and an eupnoeic respiratory motor pattern. The preparation is perfused arterially with an aqueous medium having a much lower oxygen-carrying capacity than blood. To evaluate the efficacy of the artificial perfusion in providing adequate gas exchange within the brain stem, we used polarographic Po2and pH microelectrodes to determine the tissue Po2and pH of the medulla oblongata at various depths. When the perfusate was equilibrated with 5% CO2and 95% O2, average tissue Po2was 294 Torr and no hypoxic areas were encountered. Tissue pH was remarkably uniform throughout the tissue, and on average was only 0.04 ± 0.02 pH units more acidic than that of the perfusate. Increasing the Pco2of the perfusate increased tissue Po2and decreased arterial resistance. Decreasing perfusate Pco2(while keeping pH constant) decreased tissue Po2and reduced the respiratory activity. These results suggest that arterial Pco2, independent of arterial pH, is an essential variable in determining both respiratory drive and cerebrovascular perfusion. We conclude that the medulla of the WHBP is oxygenated and within a physiological pH, which accounts for the eupneic pattern of respiratory motor activity it generates. Furthermore, this preparation may be a useful model for exploring mechanisms of central chemoreception as well as the dynamics of the cerebral vasculature responses following changes in blood gases.
Intestinal permeability is reduced and IL-10 levels are increased in septic IL-6 knockout mice
Authors: Wang Quan , Fang Cheng Hui , Hasselgren Per-Olof
Published: December 2017

Sepsis is associated with increased intestinal permeability, but mediators and mechanisms are not fully understood. We examined the role of interleukin (IL)-6 and IL-10 in sepsis-induced increase in intestinal permeability. Intestinal permeability was measured in IL-6 knockout (IL-6 −/−) and wild-type (IL-6 +/+) mice 16 h after induction of sepsis by cecal ligation and puncture or sham operation. In other experiments, mice or intestinal segments incubated in Ussing chambers were treated with IL-6 or IL-10. Intestinal permeability was assessed by determining the transmucosal transport of the 4.4-kDa marker fluorescein isothiocyanate conjugated dextran and the 40-kDa horseradish peroxidase. Intestinal permeability for both markers was increased in septic IL-6 +/+ mice but not in septic IL-6 −/− mice. Treatment of nonseptic mice or of intestinal segments in Ussing chambers with IL-6 did not influence intestinal permeability. Plasma IL-10 levels were increased in septic IL-6 −/− mice, and treatment of septic mice with IL-10 resulted in reduced intestinal permeability. Increased intestinal permeability during sepsis may be regulated by an interaction between IL-6 and IL-10. Treatment with IL-10 may prevent the increase in mucosal permeability during sepsis.
Heat shock protects L6 myotubes from catabolic effects of dexamethasone and prevents downregulation of NF-κB
Authors: Luo Guangju , Sun Xiaoyan , Hungness Eric , Hasselgren Per-Olof
Published: December 2017

Glucocorticoids are the most important mediator of muscle cachexia in various catabolic conditions. Recent studies suggest that the transcription factor NF-κB acts as a suppressor of genes in the ubiquitin-proteasome proteolytic pathway and that glucocorticoids increase muscle proteolysis by downregulating NF-κB activity. The heat shock (stress) response, characterized by the induction of heat shock proteins, confers a protective effect against a variety of harmful stimuli. In the present study, we tested the hypothesis that the heat shock response protects muscle cells from the catabolic effects of dexamethasone and prevents downregulation of NF-κB. Cultured L6 myotubes were subjected to heat shock (43°C for 1 h) followed by recovery at 37°C for 1 h. Thereafter, cells were treated for 6 h with 1 μM dexamethasone, during which period protein degradation was measured as release of TCA-soluble radioactivity from proteins that had been prelabeled with [3H]tyrosine. Heat shock resulted in increased protein and mRNA levels for heat shock protein 70. The increase in protein degradation induced by dexamethasone was prevented in cells expressing the heat shock response. In the same cells, dexamethasone-induced downregulation of NF-κB DNA binding activity was blocked. The present results suggest that the heat shock response may protect muscle cells from the catabolic effects of dexamethasone and that this effect of heat shock may be related to inhibited downregulation of NF-κB activity.
Neutralization of interleukin-18 reduces severity in murine colitis and intestinal IFN-γ and TNF-α production
Authors: Siegmund Britta , Fantuzzi Giamila , Rieder Florian , Gamboni-Robertson Fabia , Lehr Hans-Anton , Hartmann Gunther , Dinarello Charles A. , Endres Stefan , Eigler Andreas
Published: December 2017

Interleukin (IL)-18, initially described as interferon (IFN)-γ-inducing factor, is expressed in the inflamed mucosa of patients with Crohn's disease. To investigate the role of IL-18 in intestinal inflammation, the effect of neutralizing antimurine IL-18 antiserum in dextran sulfate sodium (DSS)-induced colitis in BALB/c and C57BL/6 mice was examined. During a dose response of DSS, levels of colonic IL-18 increased parallel with clinical worsening. With the use of confocal laser microscopy, the increased IL-18 was localized to the intestinal epithelial layer. Anti-IL-18 treatment resulted in a dose-dependent reduction of the severity of colitis in both BALB/c and C57BL/6 mice. Colon shortening following DSS-induced colitis was partially prevented in the treatment groups. In the colon tissue homogenates, IFN-γ concentrations were lower in the anti-IL-18-treated DSS-fed mice compared with untreated DSS-fed mice. This suppressive effect of anti-IL-18 administered in vivo was also observed on spontaneous tumor necrosis factor-α, IL-18, and IFN-γ production from ex vivo colon organ cultures. The stimulation of lamina propria mononuclear cells by IL-18 and IL-12 resulted in a synergistic increase in IFN-γ synthesis. These findings suggest that IL-18 is a pivotal mediator in experimental colitis.
Reductions in systemic oxygen delivery induce a hypometabolic state in the turtleTrachemys scripta
Authors: Platzack Björn , Hicks James W.
Published: December 2017

We investigated the effects of vagal reductions in O2delivery on oxygen consumption (V˙o2) in the anesthetized freshwater turtle Trachemys scripta. Specifically, these experiments tested the hypothesis that reductions in arterial oxygen partial pressure (Po2) and/or systemic oxygen transport (SOT) trigger a metabolic downregulation. During electric stimulation of the efferent branch of the sectioned right vagus nerve (RVEF), systemic cardiac output decreased 60–70%, systemic Po2fell by ∼30%, and SOT decreased by 60–70%. During RVEF simulation, V˙o2dropped ∼35%. During control conditions, injection of the metabolic uncoupler 2,4-dinitrophenol (DNP) more than doubledV˙o2, reflecting an increase in ATP turnover. RVEF stimulation after DNP injection produced similar cardiovascular and blood gas changes as before DNP, butV˙o2was higher than theV˙o2measured in untreated control animals, indicating that oxygen availability during RVEF stimulation is still sufficient to support V˙o2rates that are even higher than resting rates. We conclude that vagal stimulation triggers metabolic downregulation, primarily through the effects on oxygen transport, although the factor(s) that trigger the hypometabolism remain unknown. The Po2may still be an important messenger in metabolic control, but our results suggest that changes in SOT to the metabolically active tissues, rather than changes in Po2per se, play an important role in triggering hypometabolism in the freshwater turtle.
Mice deficient in oxytocin manifest increased saline consumption following overnight fluid deprivation
Authors: Amico Janet A. , Morris Mariana , Vollmer Regis R.
Published: December 2017

Male mice (9–13 mo of age) in which the gene for oxytocin (OT) had been deleted (OT −/−) were administered 0.5 M sodium chloride (NaCl) solution or tap water as a two-bottle choice test following overnight fluid deprivation (1600 to 1000 the following day). Compared with wild-type cohorts (OT +/+), OT-deficient mice ingested sevenfold greater amounts of saline in the first hour following reintroduction of fluids, P < 0.001, and fourfold greater amounts at the end of 6 h, P < 0.02. No significant difference in total water ingested was noted between the two genotypes at the end of either 1 or 6 h. If food deprivation accompanied the overnight fluid deprivation and food was reintroduced 1 h after the reintroduction of both water and saline, OT −/− mice still ingested greater amounts of saline, but not water, than OT +/+ mice at both 1 h, P < 0.001, and 6 h, P< 0.02. No differences were noted between genotypes in the daily intake of 0.5 M NaCl solution or water during a 3-day observation period before the overnight fluid deprivation. The volume of saline consumed in each 24-h observation period represented about one-tenth of the total fluids ingested in each genotype. We conclude that OT −/− mice display an enhanced salt appetite compared with OT +/+ mice when fluid deprived overnight. The salt appetite was only apparent in the presence of a perturbation such as fluid deprivation, which predisposes the animal to moderate hypovolemia. The observations support an inhibitory role for OT in the control of sodium appetite in mice.
Translational initiation is uncoupled from elongation at 18°C during mammalian hibernation
Authors: van Breukelen Frank , Martin Sandra L.
Published: December 2017

Cellular and organismal homeostasis must be maintained across a body temperature (Tb) range of 0 to 37°C during mammalian hibernation. Hibernators depress biosynthetic activities including protein synthesis, concordant with limited energy availability and temperature effects on reaction rates. We used polysome analysis to show that initiation of protein synthesis ceases during entrance into torpor in golden-mantled ground squirrels ( Spermophilus lateralis) when Tbreaches 18°C. Elongation of preinitiated polypeptides continues slowly throughout the torpor bout. As Tbbegins to rise, initiation resumes even at temperatures below 18°C, although the euthermic polysome pattern is not reestablished. At precisely 18°C, there is a large increase in initiation events and a complete restoration of euthermic polysome distribution patterns. These data indicate a role for both passive and active depression of translation during torpor and are consistent with a requirement for new protein biosynthesis during each interbout arousal.
Activation of kidney-directed neurons in the lamina terminalis by alterations in body fluid balance
Authors: Sly D. J. , McKinley M. J. , Oldfield B. J.
Published: December 2017

This study was undertaken to determine if neurons in the lamina terminalis, previously identified as projecting to the kidney (35), were responsive to alterations in stimuli associated with fluid balance homeostasis. Neurons in the lamina terminalis projecting to the kidney were identified by the retrograde transynaptic transport of Bartha's strain of pseudorabies virus in anesthetized rats. Rats were also exposed to 24-h water deprivation, intravenous hypertonic saline, or intracerebroventricular ANG II. To determine if “kidney-directed” neurons were activated following each stimulus, brain sections that included the lamina terminalis were examined immunohistochemically for viral antigen and Fos protein. With the exception of ANG II in the subfornical organ, all regions of the lamina terminalis contained neurons that were significantly activated by water deprivation, hypertonic saline, and ANG II. These results provide evidence for a neural substrate, which may underpin some of the effects of hypertonic saline and ANG II on renal function thought to be mediated through the lamina terminalis.
GLP-2 has differential effects on small intestine growth and function in fetal and neonatal pigs
Authors: Petersen Y. M. , Burrin D. G. , Sangild P. T.
Published: December 2017

Glucagon-like peptide-2 (GLP-2) is a potent intestinotropic factor in neonatal and adult animals. However, the GLP-2 responsiveness of the fetal intestine has not been established. To determine how stage of development affects the responsiveness to GLP-2, we examined GLP-2 receptor (GLP-2R) expression, gut morphology, and brush-border enzyme mRNA and activities in late-gestation fetal ( n = 7) and parenterally fed neonatal ( n = 7) piglets given GLP-2 (12.5 nmol/kg) twice daily for 6 days. The GLP-2R was expressed in the fetal and neonatal gastrointestinal tract. The biologically active GLP-2-(1–33) was undetectable (<5 pmol/l) in plasma of 98-day-gestation fetuses but increased significantly toward full term (115 days, 11 ± 1 pmol/l) and in neonates fed by total parenteral nutrition (23 ± 5 pmol/l). Exogenous GLP-2 had no effect on gut growth in fetuses but increased intestinal weight and villus height in neonates ( P < 0.05). Crypt cell proliferation and the enzymes sucrase-isomaltase, lactase-phloridzin hydrolase, aminopeptidase A, and dipeptidyl peptidase IV were unchanged by GLP-2 in both groups. Aminopeptidase N mRNA and activity were increased in fetuses, while maltase mRNA and activity were increased in neonates. In conclusion, exogenous GLP-2 had different effects on small intestine growth and function in fetuses and neonates. This may be related to the normal developmental changes in intestine growth and function and to a maturation of the GLP-2R signaling pathways around the time of birth.
Photoperiodic regulation of gene expression in brown and white adipose tissue of Siberian hamsters (Phodopus sungorus)
Authors: Demas Gregory E. , Bowers Robert R. , Bartness Timothy J. , Gettys Thomas W.
Published: December 2017

Siberian hamsters exhibit seasonal fluctuations in white adipose tissue (WAT) mass, with peaks in long “summerlike” days (LDs) and nadirs in short “winterlike” days (SDs). These responses can be mimicked in the laboratory after transfer from LDs to SDs. The purpose of the present study was to test whether changes in WAT and brown adipose tissue (BAT) gene expression that are mediated by the sympathetic nervous system in other obesity models are also associated with seasonal adiposity changes in Siberian hamsters. SDs decreased WAT mass and leptin mRNA, increased WAT β3-adrenoceptor mRNA, and induced retroperitoneal WAT uncoupling protein-1 mRNA (the latter measured by RT-PCR, others measured by ribonuclease protection assay) while increasing BAT uncoupling protein-1 and peroxisome proliferator-activated receptor-γ coactivator-1 mRNAs. These effects were not due to SD-induced gonadal regression and largely occurred before the usual SD-induced decreases in food intake. Thus the SD-induced decreased adiposity of Siberian hamsters may be due to a coordinated suite of WAT and BAT gene transcription changes ultimately increasing lipid mobilization and utilization.
Sensitivity of CO2excretion to blood flow changes in trout is determined by carbonic anhydrase availability
Authors: Desforges Patrick R. , Harman Stuart S. , Gilmour Kathleen M. , Perry Steve F.
Published: December 2017

The blood transit time through the gills of rainbow trout ( Oncorhynchus mykiss) was modified by manipulation of cardiac output (V˙b). The experiments tested the hypothesis that efficiency of CO2excretion is sensitive to changes in blood flow owing to chemical equilibrium limitations. An extracorporeal blood shunt was used to continuously monitor blood gases in fish in which V˙b was elevated (by 13.3 ± 2.4 ml · min−1· kg−1) by intravascular saline injection or reduced (by 10.8 ± 1.8 ml · min−1· kg−1) by removal of plasma. The arterial partial pressure of CO2(PaCO2; an index of CO2excretion efficiency) was increased with elevated V˙b and was decreased with reduced V˙b such that the changes in PaCO2exhibited a significant positive sigmoidal relationship with the changes in V˙b ( r2=0.75; P< 0.05). In contrast, there was no significant relationship between changes in the arterial partial pressure of O2(PaO2; an index of O2uptake efficiency) and changes in V˙b ( r2= 0.07; P > 0.05). The intravenous administration of carbonic anhydrase (CA; 10 mg/kg) before vascular volume loading eliminated the increase in PaCO2with increased V˙b that was observed in control fish.
Effect of inspiration on inferior vena caval blood flow in dogs
Authors: Lloyd T. C.
Published: December 2017

Inferior vena cava flow of anesthetized open-chest dogs was drained to a reservoir from a cannula above the diaphragm and returned to the atrium at constant rate. At selected base-line caval pressures, the caval flow and pressures in the abdomen (Pab), iliac vein (Piv), and downstream cavae (Pvc) were recorded during spontaneous breathing, cyclic phrenic nerve stimulation, and cyclic lowering of caval drain pressure. Each augmented flow unless Pab exceeded Pvc by at least ca. 5 cmH2O. In other dogs a cannulating flow probe was placed in the thoracic inferior cava and the chest was reclosed. Flow was augmented throughout most or all of spontaneous inspiration and was never depressed even though Pab exceeded right atrial pressure and Piv. I conclude that the collapse of hepatic veins and proximate cava does not occur at most normal pressures and a Starling resistor analog of abdominal veins based solely on abdominal and venous pressures is inappropriate. Both falling atrial pressure and rising Pab probably augment inspiratory abdominal venous return.
Response of bronchial smooth muscle to mast cell degranulation in situ
Authors: Garrity E. R. , Stimler N. P. , Munoz N. M. , Fried R. , Leff A. R.
Published: December 2017

We studied the response of bronchial smooth muscle to mast cell degranulation with Ascaris suum antigen (AA) and compound 48/80 (48/80) in 26 mongrel dogs in situ. Bronchial smooth muscle response was measured isometrically in situ from a segment of the right middle lobe bronchus; tracheal response was monitored isometrically as a control. After intra-arterial (ia) injection of AA into the bronchial circulation, bronchial contraction preceded tracheal contraction by 19.2 +/- 4.6 s (P less than 0.002). Bronchial contraction to AA (21.7 +/- 3.4 g) was substantially greater than to 48/80 (10.5 +/- 1.8 g, P less than 0.05) corresponding to differences in maximal systemic histamine concentrations (146 +/- 24.1 vs. 1000 +/- 236 ng/ml, P less than 0.01). In 5 dogs, the effect of leukotriene D4 (LTD4) and FPL 55712 was studied. Injection of 10(-8) mol ia LTD4 caused no bronchial contraction. In four dogs, 10(-7) mol FPL 55712 caused no bronchial relaxation after initial precontraction during immune degranulation with AA; intravenous chlorpheniramine (5 mg/kg) caused 69.7 +/- 9.4% relaxation. We demonstrate a model that permits selective immune degranulation of a single major resistance bronchus in situ. We conclude that AA-induced degranulation in dogs caused bronchial contraction predominantly by secretion of preformed mediator.
Respiratory-related activity of upper airway muscles in anesthetized rabbit
Authors: Rothstein R. J. , Narce S. L. , deBerry-Borowiecki B. , Blanks R. H.
Published: December 2017

The electromyographic activity of the glossal, suprahyoid, infrahyoid, and pharyngeal muscles was examined during spontaneous respiration in rabbits anesthetized with ketamine hydrochloride. This activity was then correlated with phases of the respiratory cycle. Our findings indicate that the overwhelming majority of the muscles comprising these groups show activity that increased during inspiration and returns to the background level during expiration and the end-expiratory pause. The exceptions are the inferior pharyngeal constrictor muscle, which demonstrates increased activity during expiration and the end-expiratory pause, and the stylohyoid major and digastric muscles, whose activity was not modulated with respiration. In general, the results obtained under ketamine anesthesia are in agreement with the studies on a more limited number of muscles in humans during sleep or in animal studies utilizing light anesthesia. Furthermore, the use of ketamine avoids the central suppressant effects produced by barbituate anesthesia. It has been argued that the upper airway muscles are rhythmically active during respiration to maintain the patency of the upper airway. Both the number of muscles that are rhythmically active and their strict correlation with specific phases of the respiratory cycle suggest that the forces exerted on the upper airway are complex and that peak tension is generated during inspiration. Further studies are required to evaluate the effects of ketamine anesthesia on these upper airway muscles before this rabbit model can be utilized to examine respiratory disorders of the upper airway.
Characteristics of sodium transport by excised rabbit trachea
Authors: Boucher R. C. , Gatzy J. T.
Published: December 2017

We studied factors that might be expected to influence Na+ absorption, the major active ion transport by excised rabbit trachea. Transepithelial electric potential difference (PD), short-circuit current (Isc), conductance (G), and unidirectional 22Na+ and 36Cl- flows were measured before and during exposure to a drug or after a change in bathing solution composition. Ouabain (3 X 10(-4) M) in the submucosal bath abolished Isc and Na+ absorption but increased G and unidirectional Cl- flows. Luminal amiloride (10(-3) M) abolished net Na+ absorption but reduced Isc by only 40%. Residual Isc was accounted for by induction of net Cl- secretion, which resulted from a reduction in mucosal (m)-to-submucosal (s) Cl- flux (J). Replacement of luminal Na+ by choline induced effects similar to those of amiloride. Residual Isc was not reduced by mucosal indomethacin (10(-6) M). Replacement of luminal Cl- by gluconate raised transepithelial PD fourfold, raised Isc 50%, decreased G 60%, and abolished net Na+ absorption by decreasing Jm leads to s and increasing Js leads to m. Luminal amphotericin B affected bioelectric properties and ion flows minimally, whereas monensin (10(-4) M) decreased Isc and net Na+ transport. Antidiuretic hormone (ADH, 1 U/ml) or aldosterone (10(-6) M) did not affect in Isc or PD after exposure up to 6 h. We conclude that 1) Na+ absorption across the rabbit trachea is ouabain sensitive, 2) the entry step for Na+ across the luminal membrane is amiloride sensitive, 3) Cl- secretion induced by amiloride or luminal Na+ replacement probably reflects a more favorable chemical gradient for basolateral coupled NaCl entry and/or electrical gradient for Cl- efflux across the luminal membrane, 4) the coupling of Na+ entry to the presence of Cl- in the mucosal solution is probably an electrical rather than a chemical cotransport process, and 5) the tracheal epithelium of the rabbit is not a target for aldosterone and ADH.
A model evaluation of estimates of breath-to-breath alveolar gas exchange
Authors: Swanson G. D. , Sherrill D. L.
Published: December 2017

A mathematical model has been implemented for evaluation of methods for estimating breath-to-breath alveolar gas exchange during exercise in humans. This model includes a homogeneous alveolar gas exchange compartment, a dead space compartment, and tissue spaces for CO2 (alveolar and dead space). The dead space compartment includes a mixing portion surrounded by tissue and an unmixed (slug flow) portion which is partitioned between anatomical and apparatus contributions. A random sinusoidal flow pattern generates a breath-to-breath variation in pulmonary stores. The Auchincloss algorithm for estimating alveolar gas exchange (Auchincloss et al., J. Appl. Physiol. 21: 810-818, 1966) was applied to the model, and the results were compared with the simulated gas exchange. This comparison indicates that a compensation for changes in pulmonary stores must include factors for alveolar gas concentration change as well as alveolar volume change and thus implies the use of end-tidal measurements. Although this algorithm yields reasonable estimates of breath-to-breath alveolar gas exchange, it does not yield a “true” indirect measurement because of inherent error in the estimation of a homogeneous alveolar gas concentration at the end of expiration.
Bronchial responsiveness to methacholine and effects of respiratory maneuvers
Authors: Sestier M. , Pineau L. , Cartier A. , Martin R. R. , Malo J. L.
Published: December 2017

Eight asthmatic and six normal subjects had methacholine chloride inhalation tests on two visits. On first assessment the provocative concentration causing a 20% fall in forced expiratory volume in 1 s (PC20FEV1) was measured. On the second visit the provocative concentration causing a 35% fall in specific lung conductance (PC35sGL) was obtained in addition to the PC20FEV1. Lung resistance was continuously monitored to evaluate the bronchomotor effect of FEV1 maneuver. Results of PC20FEV1 were within one single twofold concentration on the two visits. In all subjects but one PC35sGL was lower than PC20FEV1, and in 10 instances this difference was superior to a single twofold concentration. The bronchodilator effect of FEV1 maneuver was significantly although loosely related to base-line airway caliber and excitability. However, we were unable to show a significant relationship between the differences between PC20FEV1 and PC35sGL and this bronchodilator effect. This suggests that other factors may explain the greater sensitivity of PC35sGL compared with PC20FEV1.
Mechanics of the respiratory system and breathing pattern during sleep in normal humans
Authors: Hudgel D. W. , Martin R. J. , Johnson B. , Hill P.
Published: December 2017

The purposes of this investigation were to describe the changes in 1) dynamic compliance of the lungs, 2) airflow resistance, and 3) breathing pattern that occur during sleep in normal adult humans. Six subjects wore a tightly fitting face mask. Flow and volume were obtained from a pneumotachograph attached to the face mask. Transpulmonary pressure was calculated as the difference between esophageal pressure obtained with a balloon and mask pressure. At least 20 consecutive breaths were analyzed for dynamic compliance, airflow resistance, and breathing pattern during wakefulness, non-rapid-eye-movement stage 2 and rapid-eye-movement (REM) sleep. Dynamic compliance did not change significantly. Airflow resistance increased during sleep; resistance was 3.93 +/- 0.56 cmH2O X 1–1 X s during wakefulness, 7.96 +/- 0.95 in stage 2 sleep, and 8.66 +/- 1.43 in REM sleep (P less than 0.02). By placing a catheter in the retroepiglottic space and thus dividing the airway into upper and lower zones, we found the increase in resistance occurred almost entirely above the larynx. Decreases in tidal volume, minute ventilation, and mean inspiratory flow observed during sleep were not statistically significant.
Variable inhibition by falling CO2 of hypoxic ventilatory response in humans
Authors: Moore L. G. , Huang S. Y. , McCullough R. E. , Sampson J. B. , Maher J. T. , Weil J. V. , Grover R. F. , Alexander J. K. , Reeves J. T.
Published: December 2017

Acute hypoxia stimulates an increase in ventilation but the resulting hypocapnia limits the magnitude of the increase. Thus the hypoxic ventilatory response is usually measured during isocapnia, but this may not reflect events at high altitude. We hypothesized that the degree of inhibition by hypocapnia might depend on individual ventilatory response to CO2 and thus vary between persons. To test this hypothesis we compared the isocapnic hypoxic ventilatory response (end-tidal PCO2 maintained by CO2 addition) with the response in which CO2 was not added and the end-tidal PCO2 fell to a variable extent (poikilocapnic hypoxia). In 14 healthy persons we found that the poikilocapnic hypoxic ventilatory response was determined by two factors: sensitivity to isocapnic hypoxia acting to increase ventilation and sensitivity to CO2 acting to decrease the hypoxic ventilatory response. The ventilatory response to poikilocapnic hypoxia correlated with but was generally less than the isocapnic hypoxic response. The magnitude of the difference between them related to the hypercapnic response. Further, the results suggested that the CO2 response in the high CO2 range related to ventilatory events in the low CO2 range. Thus the magnitude of ventilatory inhibition by hypocapnia may depend on individual ventilatory responsiveness to CO2.
Neuromuscular blockade enhances phrenic nerve activity during high-frequency ventilation
Authors: England S. J. , Onayemi A. , Bryan A. C.
Published: December 2017

Phrenic nerve activity was monitored in anesthetized cats during high-frequency ventilation (HFV). Rhythmic phrenic discharge disappeared during HFV in all animals at normal arterial PCO2 levels. Rhythmic activity returned after neuromuscular blockade in the vagally intact animal. Although vagotomy alone also restored phrenic discharge, this activity was further enhanced by subsequent neuromuscular blockade. Therefore we suggest that apnea during HFV results from inspiratory inhibition mediated by both chest wall and vagal afferent mechanisms.
Diphasic ventilatory response to hypoxia in newborn lambs
Authors: Bureau M. A. , Zinman R. , Foulon P. , Begin R.
Published: December 2017

The ventilatory response of newborn lambs to hypoxemia was evaluated in two groups of seven awake lambs studied at 2 and 7 days of life. Minute ventilation (VE) and airway occlusion pressure (P0.1) were monitored as the animals were exposed in sequence to room air, 12% O2 (15 min), 7% O2 (15 min), and room air. On 12 and 7% O2, 2-day-old lambs experienced a brisk hyperventilation followed by a VE depression, previously described in newborns of other species (diphasic response). The 7-day-old lambs had a clear diphasic VE response only on 7% O2 breathing. In the 2-day-old lambs, at the time of the relative VE depression to 12% O2, the respiratory centers showed a persisting responsiveness to further hypoxia; switching to 7% O2 caused a brisk increase in VE and P0.1 of 70 and 130%, respectively, which was followed again by a VE depression. The magnitude of the immediate VE response to hypoxia, taken as an index of the chemoreceptor strength, was inversely related to the magnitude of the VE depression (R = 0.81, P less than 0.001). It was concluded that 1) lambs as well as other neonates have an age-related diphasic VE response to hypoxia; 2) at the time of the VE depression, the respiratory centers maintain their responsiveness to further acute hypoxia; and 3) the weakness of the chemoreceptors in the newborn is a major determinant of the diphasic response.
Pulmonary vasoconstrictor response to acute decrease in blood P50
Authors: Teisseire B. P. , Soulard C. D.
Published: December 2017

The O2 sensor that triggers hypoxic pulmonary vasoconstriction may be sensitive not only to alveolar hypoxia but also to hypoxia in mixed venous blood. A specific test of the blood contribution would be to lower mixed venous PO2 (PvO2), which can be accomplished by increasing hemoglobin-O2 affinity. When we exchanged transfused rats with cyanate-treated erythrocytes [PO2 at 50% hemoglobin saturation (P50) = 21 Torr] or with Creteil erythrocytes (P50 = 13.1 Torr), we lowered PvO2 from 39 +/- 5 to 25 +/- 4 and to 14 +/- 4 Torr, respectively, without altering arterial blood gases or hemoglobin concentration. Right ventricular systolic pressure increased from 32 +/- 2 to 36 +/- 3 Torr with cyanate erythrocytes and to 44 +/- 5 Torr with Creteil erythrocytes. Cardiac output was unchanged. Control exchange transfusions with normal rat or 2,3-diphosphoglycerate-enriched human erythrocytes had no effect on PvO2 or right ventricular pressure. Alveolar hypoxia plus high O2 affinity blood caused a greater increase in right ventricular systolic pressure than either stimulus alone. We concluded that PvO2 is an important determinant of pulmonary vascular tone in the rat.
Angiotensin is not required for hypoxic constriction in salt solution-perfused rat lungs
Authors: McMurtry I. F.
Published: December 2017

It has been reported that angiotensin II is specifically required for hypoxic vasoconstriction in rat lungs perfused with physiological salt solution. However, studies with other preparations indicate that angiotensin II does not play a necessary role in the mechanism of hypoxic vasoconstriction. In an attempt to resolve this disagreement I investigated in salt solution-perfused rat lungs whether vasoactive agents other than angiotensin II would induce hypoxic vasoconstriction, and, if so, whether the effect was due to selective action on the hypoxic mechanism or to a nonspecific increase in vascular reactivity. The results showed the development of hypoxic pressor responses after addition to perfusate of plasma, angiotensin II, KCl, vanadate, 4-aminopyridine, or norepinephrine plus propranolol. In contrast, addition of saline (control), ouabain, or tetraethylammonium chloride did not induce hypoxic vasoconstriction. Saralasin inhibited the effect of angiotensin II, but not that of plasma. Induction of responsiveness to hypoxia was associated with an increase in normoxic perfusion pressure and with potentiation of pressor responses to KCl. These results suggest that angiotensin II does not play a unique, integral role in the hypoxic mechanism, but instead is only one of many substances that will induce hypoxic pressor reactivity by reversing the vascular hyporeactivity of salt solution-perfused rat lungs.
Responses to chemical stimulation of upper airway muscles diaphragm in awake cats
Authors: Haxhiu M. A. , van Lunteren E. , Mitra J. , Cherniack N. S.
Published: December 2017

The steady-state and transient effects of hyperoxic hypercapnia on the electromyographic activities of the genioglossus (GG), posterior cricoarytenoid (PCA), and diaphragm (D) were studied in conscious unsedated cats with chronically implanted electrodes. Hypercapnia (inhalation of 3.4 and 7.4% CO2 in O2) increased the phasic electrical activity occurring during inspiration in all three muscles and also increased tonic activity of the GG. The GG responded to steady-state CO2 inhalation alinearly and with larger increases in activity than the PCA and D. Phasic GG activity was present in only 4 of 10 cats breathing 100% O2, whereas phasic PCA and D activity could be observed in all animals studied. When gas mixtures containing CO2 were given, the GG reached its new steady-state level more slowly than the D or PCA, and when CO2 was rapidly removed from the inspired gas mixture, the GG attained its steady state sooner than either the PCA or D. These results suggest that in awake unsedated animals, chemical stimuli do not affect either transient or steady-state responses of the GG in the same way as the D. These differences seem to be explained mainly by different threshold characteristics of hypoglossal and phrenic neurons but also in part by dissimilarities in their steady-state responses.
Effect of background loading on perception of inspiratory loads
Authors: Revelette W. R. , Zechman F. W. , Parker D. E. , Wiley R. L.
Published: December 2017

The effect of background loading on magnitude estimation of added elastic and resistive inspiratory loads was determined. An analogous study involving estimation of the heaviness of weights in the hand was also performed. Perceptual performance was assessed using Stevens' power law psi = k phi n, where psi is the subjective magnitude, phi is the peak mouth pressure generated with an inspiratory load or the weight of the load in grams for the heaviness estimation, and the exponent n characterizes perceptual performance. The value of n was determined for the control and background conditions for each study. The results for both inspiratory loading studies and the heaviness estimation experiment indicate that background loading is associated with a significant increase in the exponent for magnitude estimation (P less than 0.05). Adjustment of the stimulus scale by subtracting the difference in peak mouth pressures generated during resting breathing between control and background-loaded conditions for the inspiratory loading studies, or the weight of the background load in the heaviness estimation experiment, converted the exponents obtained under background-loaded conditions to values that were not significantly different from those for control (P greater than 0.05). These results are consistent with the theory suggesting that an increase in detection threshold, produced by the background load, is responsible for the increase in exponent for magnitude estimation.
Ventilation-perfusion relationship during high-frequency ventilation
Authors: Brusasco V. , Knopp T. J. , Schmid E. R. , Rehder K.
Published: December 2017

The efficiency of oxygenation and the uniformity of the distribution of regional ventilation (Vr) to regional perfusion (Qr) along the vertical and horizontal axes was compared in anesthetized dogs between conventional mechanical ventilation (CMV) and high-frequency ventilation (HFV) at 5.8, 15.0, and 29.8 Hz. Both CMV and HFV were adjusted to result in similar arterial CO2 tensions. The distribution of Vr/Qr during HFV at 5.8 Hz tended to be more uniform than during HFV at 15.0 or 29.8 Hz or during CMV. Consistent with this observation, arterial O2 tension (PaO2) tended to be higher during HFV at 5.8 Hz (means +/- SD, 90 +/- 9 Torr) than during HFV at 15.0 Hz (83 +/- 9 Torr) or 29.8 Hz (78 +/- 10 Torr); PaO2 was significantly higher during HFV at 5.8 Hz than during CMV (83 +/- 7 Torr).
Ventilatory muscles during exercise in air and oxygen in normal men
Authors: Bye P. T. , Esau S. A. , Walley K. R. , Macklem P. T. , Pardy R. L.
Published: December 2017

To determine whether normal ventilatory muscles fatigue during short-term high-intensity exercise, we measured diaphragmatic electromyogram (EMG, esophageal electrode), and pleural (Ppl), gastric (Pga), and transdiaphragmatic (Pdi) pressures in seven normal young men. On separate days, the subjects performed exercise to exhaustion at a constant work load (80% maximum power output) inspiring air or 40% O2. Before and after exercise, Pdimax and maximum expiratory pressure at the mouth (PEmax) were measured. At 0.5–2 min postexercise, there was a decrease in Pdimax in both air (P less than 0.02) and O2 studies (P less than 0.05). There was some recovery in Pdimax from 2–5 min postexercise in air (P less than 0.05) and complete recovery 2–5 min postexercise in O2. PEmax did not change postexercise. During exercise in air, the EMG predicted diaphragmatic fatigue in five subjects using a 20% fall of the ratio of high-frequency (150–350 Hz) to low-frequency) (20–46 Hz) power (H/L) as the criterion. Further evidence of diaphragmatic fatigue during exercise in air in two subjects was the decrease in end-inspiratory Pdi toward end exercise. There was an increase in exercise time with O2 (P less than 0.05). The improved performance in O2 was associated with a delay in the fall in H/L and the absence of the decrease in end-inspiratory Pdi in those subjects in whom such changes were observed in air.(ABSTRACT TRUNCATED AT 250 WORDS)
Phasic volume-related feedback on upper airway muscle activity
Authors: van Lunteren E. , Strohl K. P. , Parker D. M. , Bruce E. N. , Van de Graaff W. B. , Cherniack N. S.
Published: December 2017

The effects of vagally mediated volume-related feedback on the activity of upper airway muscles was assessed in nine pentobarbital-anesthetized, tracheostomized, spontaneously breathing dogs. Moving average electrical activity was recorded before and during single-breath airway occlusions from the genioglossus, posterior cricoarytenoid, and alae nasi muscles and compared with simultaneously recorded tidal volume and electrical activity of the phrenic nerve (6 dogs) or diaphragm (3 dogs). The normally early peak of upper airway muscle activity during unoccluded breaths was delayed to late or end inspiration during occluded breaths. Inspiratory depression started at a lower volume above end-expiratory volume and at an earlier time after inspiratory onset for the upper airway muscles than for the phrenic nerve and the diaphragm. The amount of depression at the end of inspiratory airflow was larger for all of the upper airway muscles than for the phrenic nerve and diaphragm. Depressive effects were most prominent in the genioglossus, followed by the posterior cricoarytenoid and the alae nasi. After vagotomy, depressive effects of volume-related feedback were no longer seen. These results suggest that activity of the upper airway muscles is modulated by vagally mediated feedback, apparently to a larger extent than that of the diaphragm and phrenic nerve.
Source of the fluid component of secretions from tracheal submucosal glands in cats
Authors: Corrales R. J. , Nadel J. A. , Widdicombe J. H.
Published: December 2017

The idea that the fluid component of cat tracheal submucosal gland secretions is produced by Na-linked secretion of Cl was tested. Gland secretion was stimulated with phenylephrine; gland fluid flow, net salt movement, and output of 35SO4-labeled macromolecules were measured. With CI, I, NO3, or Br as the major anion, phenylephrine caused equal increases in gland flow and output of 35S-labeled macromolecules while increasing net transepithelial 22Na movement from 0 to about 10 mu eq X cm-2 X h-1. With the impermeant gluconate as a major anion, phenylephrine caused the same increase in output of 35S label, a smaller increase in gland flow, and had no effect on net 22Na movement. Short circuiting in the presence of Cl, or high concentrations of the loop diuretics, furosemide or bumetanide, did not alter the actions of phenylephrine. Ouabain or replacement of Na by choline or Li abolished all secretory effects of phenylephrine. We conclude that active Cl secretion is not responsible for the transepithelial flows of salt and water induced by phenylephrine. Instead, these flows may be secondary to the release of osmotically active components of the secretory granules.
Adaptations of skeletal muscle to endurance exercise and their metabolic consequences
Authors: Holloszy J. O. , Coyle E. F.
Published: December 2017

Regularly performed endurance exercise induces major adaptations in skeletal muscle. These include increases in the mitochondrial content and respiratory capacity of the muscle fibers. As a consequence of the increase in mitochondria, exercise of the same intensity results in a disturbance in homeostasis that is smaller in trained than in untrained muscles. The major metabolic consequences of the adaptations of muscle to endurance exercise are a slower utilization of muscle glycogen and blood glucose, a greater reliance on fat oxidation, and less lactate production during exercise of a given intensity. These adaptations play an important role in the large increase in the ability to perform prolonged strenuous exercise that occurs in response to endurance exercise training.
Effect of edema and hemodynamic changes on extravascular thermal volume of the lung
Authors: Gray B. A. , Beckett R. C. , Allison R. C. , McCaffree D. R. , Smith R. M. , Sivak E. D. , Carlile P. V.
Published: December 2017

The extravascular thermal volume of the lung (ETV) has been measured in dogs as the difference between mean transit time (t) volumes for heat and indocyanine green dye across the pulmonary circulation, calculated as the product of thermal dilution cardiac output (CO) and the difference in t for aortic indicator-dilution curves generated by right and left atrial injections. ETV measurements were compared with the extravascular lung mass (ELM): in 21 normal dogs, ETV/ELM = 1.11 +/- 0.14 (SD); in 17 dogs with hydrostatic pulmonary edema (up to 21 g/kg), ETV/ELM = 0.90 +/- 0.11; and in 27 dogs with alloxan pulmonary edema (up to 51 g/kg); ETV/ELM = 0.93 +/- 0.13. For all 65 dogs the mean ETVELM was 0.98 +/- 0.15, and the liner regression was ETV (ml/kg) = 0.90 ELM (g/kg) + 0.86 +/- 2.25 (SEE; r = 0.96). Calculations based on measurements of lung specific heat predict that ETV/ELM should equal 0.984. With acute changes in pulmonary hemodynamics, ETV was reduced by reductions in pulmonary arterial pressure (Ppa) sufficient to produce zone 1 conditions at the top of the lung. However, ETV was not affected by increases in CO (mean = 50%) produced by nitroprusside or by increases in Ppa and pulmonary blood volume (mean = 27%) produced by partial mitral valve obstruction. Distortion of the thermal dilution curve due to position of the arterial thermistor appears to be the greatest source of variability and overestimation. Simultaneous measurements from pairs of thermistors differed by 14% (range 0.4–50%).
Effect of puberty and estradiol on hypoxic vasomotor response in isolated sheep lungs
Authors: Wetzel R. C. , Zacur H. A. , Sylvester J. T.
Published: December 2017

We previously reported that in isolated lungs from 6-mo-old sheep acute hypoxia caused a greater vasoconstrictor response in males than in females but that this response in castrated males was not different from noncastrated males. To determine whether a gender difference exists before puberty, we compared the steady-state stimulus-response relationship of the pulmonary circulation to graded hypoxia in isolated perfused lungs of juvenile 2-mo-old male and female sheep. The flow-resistive properties of the pulmonary vessels were assessed by pressure-flow curves generated over a wide range of flows (0–150 ml X min-1 X kg-1) at six different levels of inspired O2 tension (PIO2) between 200 and 0 Torr. The stimulus-response relationship, quantified by plotting the pulmonary arterial pressure at a flow of 50 ml X min-1 X kg-1 against PIO2 was the same in juvenile male and female sheep lungs. Furthermore, the responses of juvenile sheep were not different from those of 6-mo-old males and were greater than those of 6-mo-old females. Treatment with 17 beta-estradiol (10–20 mg im) 2–5 days prior to perfusion significantly attenuated the response in the lungs from both 2-mo-old female and 6-mo-old castrated male sheep. We conclude that the gender difference in the hypoxic stimulus-response relationship observed in isolated lungs from 6-mo-old sheep arises from attenuation in the female at the time of puberty. This attenuation may be mediated by estradiol.
Salutary effect of fall in abdominal pressure during diaphragm paralysis
Authors: Kelly S. , Zin W. A. , Decramer M. , De Troyer A.
Published: December 2017

To examine the mechanical effects of the fall in abdominal pressure (Pab) that occurs during inspiration in diaphragmatic paralysis, we studied lung inflation and rib cage expansion before and after the abdomen was opened in nine spontaneously breathing dogs with bilateral phrenicotomy . We measured Pab, tidal volume, and parasternal electromyographic (EMG) activity during quiet breathing and CO2-induced hyperpnea. In six dogs, we also measured changes in anteroposterior and transverse rib cage diameters, the resting length of the parasternal intercostal muscles, and the amount of shortening of these muscles during inspiration. Opening the abdomen caused a marked reduction in the fall in Pab during inspiration and invariably resulted in a decrease in tidal volume (mean decrease, 13%), which contrasted with marked increases in inspiratory rib cage expansion and in the amount of parasternal intercostal shortening. The procedure, however, did not affect the resting length or inspiratory EMG activity of the parasternals . These findings indicate that although the fall in Pab, which occurs during inspiration in diaphragmatic paralysis, causes paradoxical inward displacement of the ventral abdominal wall, it has a salutary effect on tidal volume. This phenomenon is probably due to the fact that the diaphragm is part of the abdominal wall.