bluuebunny/crossref_metadata_2025 huggingface dataset:
Depression of hypoxic ventilatory response in humans by somatostatin
Authors: Filuk R. B. , Berezanski D. J. , Anthonisen N. R.
Published: December 2017

In nine normal subjects we measured the ventilatory response to isocapnic hypoxia with and without an intravenous infusion of 1 mg of somatostatin. Arterial O2 saturation was rapidly lowered to 80 +/- 2% in 2 min and maintained for 30 min. During control experiments, ventilation increased immediately (3-5 min) and then declined so that at 25 min of hypoxia ventilation was little above that in room air. Somatostatin was associated with a small decrease in ventilation while the subjects breathed room air. With hypoxia there was no immediate increase in ventilation for the group as a whole, although an increase was observed in one subject. With somatostatin, after 25 min of hypoxia, mean ventilation was lower than at any other time in the study; as hypoxia was discontinued ventilation increased slightly. Somatostatin causes profound depression of the ventilatory response to hypoxia by a mechanism that is not known but may be central. With somatostatin hypoxia of 25-min duration tends to depress ventilation.
Nedocromil sodium in allergen-induced bronchial responses and airway hyperresponsiveness in allergic sheep
Authors: Abraham W. M. , Stevenson J. S. , Eldridge M. , Garrido R. , Nieves L.
Published: December 2017

We examined the effects of nedocromil sodium, a new drug developed for the treatment of reversible obstructive airway disease, on allergen-induced early and late bronchial responses and the development of airway hyperresponsiveness 24 h after challenge in nine allergic sheep. On occasions greater than 2 wk apart the sheep were treated with 1) placebo aerosol (buffered saline) before and 3 h after antigen challenge, 2) an aerosol of nedocromil sodium (1 mg/kg in 3 ml buffered saline) before antigen challenge and placebo 3 h after challenge, and 3) placebo aerosol before and nedocromil sodium aerosol 3 h after challenge. Early and late bronchial responses were determined by measuring specific lung resistance (sRL) before and periodically after challenge. Airway responsiveness was assessed by determining from dose-response curves the carbachol concentration (in % wt/vol) that increased sRL to 5 cmH2O/s. In the placebo trial, antigen challenge resulted in early and late increases in sRL over a base line of 353 +/- 32 and 131 +/- 17% (SE), respectively. Both early and late increases in sRL were blocked (P less than 0.05) when the sheep were pretreated with nedocromil sodium. When nedocromil was given after the early response, the late response was reduced significantly. Eight of nine sheep developed airway hyperresponsiveness 24 h after antigen challenge. In these eight sheep, carbachol concentration before antigen challenge was 2.6 +/- 0.3%, 24 h later carbachol concentration was significantly lower (1.8 +/- 0.3%). Both nedocromil sodium treatments blocked (P less than 0.05) this antigen-induced airway hyperresponsiveness.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of positive-pressure ventilatory frequency on regional pleural pressure
Authors: Novak R. , Matuschak G. M. , Pinsky M. R.
Published: December 2017

Regional lung ventilation is modulated by the spatiotemporal distribution of alveolar distending forces. During positive-pressure ventilation, regional transmission of airway pressure (Paw) to the pleural surface may vary with ventilatory frequency (f), thus changing interregional airflow distribution. Pendelluft phenomena may result owing to selective regional hyperventilation or phase differences in alveolar distension. To define the effects of f on regional alveolar distension during positive-pressure ventilation, we compared regional pleural pressure (Ppl) swings from expiration to inspiration (delta Ppl) and end-expiratory Ppl over the f range 0-150 min-1 in anesthetized, paralyzed, close-chested dogs with normal lungs. We inserted six pleural balloon catheters to analyze Ppl distribution along three orthogonal axes of the right hemithorax. Increases in regional Ppl were synchronously coupled with inspiratory increases in Paw regardless of f. However, at a constant tidal volume and percent inspiratory time, end-expiratory Paw and Ppl increased in all regions once a f threshold was reached (P less than 0.01). Supradiaphragmatic delta Ppl were less than in other regions (P less than 0.05), but thoracoabdominal binding abolished this difference by decreasing thoracoabdominal compliance. We conclude that the distribution of forces determining dynamic regional alveolar distension are temporally synchronous but spatially asymmetric during positive-pressure ventilation at f less than or equal to 150/min.
Respiratory resetting induced by spinal cord stimulation in the cat
Authors: Speck D. F.
Published: December 2017

Electrical stimulation (50-150 microA, 0.5-ms duration, 3-300 Hz) was performed within three different regions (lateral, ventrolateral, and ventral) of the C2-C3 spinal cord of decerebrate, vagotomized, paralyzed, and artificially ventilated cats. Spinal cord stimulation sites were located by inserting monopolar or bipolar stimulating electrodes either at the dorsolateral sulcus or at least 1 mm medial or lateral to the sulcus. With stimulation at each site, alterations in respiratory rhythm, orthodromic phrenic nerve responses, and antidromic activation of medullary respiratory-modulated neurons were examined. Phrenic nerve responses to cervical spinal cord stimulation consisted of an early excitation (2-4 ms) and/or a late excitation (4-8 ms). Stimulation of the lateral region evoked the greatest amplitude early response and stimulation of the ventrolateral region produced the greatest late excitation. All three stimulus sites elicited antidromic activation of some respiratory-modulated neurons in the dorsal (DRG) and ventral respiratory groups (VRG). The lateral region was the least effective resetting site, and it had the highest incidence of antidromic activation of both DRG and VRG neurons. The ventrolateral region of the cervical spinal cord was the most effective resetting site, but it had the lowest incidence of antidromic activation of DRG respiratory-modulated neurons. In addition, resetting responses were observed with spinal cord stimulation at similar sites in the thoracic and lumbar spinal cord regions thought to be devoid of inspiratory bulbospinal axons.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of changes in left ventricular loading and pleural pressure on mitral flow
Authors: Robotham J. L. , Stuart R. S. , Borkon A. M. , Doherty K. , Baumgartner W.
Published: December 2017

The cause of the fall in left ventricular (LV) stroke volume (SV) during a fall in pleural pressure (Pp1) has been in dispute for over a century. We have defined the changes in the temporal relationship between LV inflow (Qm) and outflow (Qa) in a canine preparation to test the mutually exclusive hypotheses that the fall in LVSV is caused only by changes during diastole (e.g., ventricular interdependence) or only by changes during systole (e.g., afterload). The ability of the experimental preparation to measure the results of acute changes in right heart volume or output and acute changes in LV afterload was validated in open-chest studies with and without pericardial constraint. In closed-chest studies, with a fall in Pp1 during a Mueller maneuver Qm reached both its inspiratory minimum and expiratory maximum before Qa in 80% of the Mueller maneuvers, invalidating both hypotheses, which each required that one flow lead the other in 100% of the Mueller maneuvers. Review of individual records suggested that if the rapid changes in Pp1 occurred during systole, Qa could vary in a manner independent of the preceding Qm. These studies suggest that both diastolic and systolic events may contribute to the fall in SV, while causing opposite changes in LV volumes.
Determinants of platelet kinetics: effects of pulmonary microembolism
Authors: McCandless B. K. , Kaplan J. E. , Cooper J. A. , Malik A. B.
Published: December 2017

We examined the mechanisms of platelet uptake in the lungs after alpha-thrombin-induced pulmonary microembolism. Platelets labeled with 111In-oxine were reinfused into chronically prepared sheep. Pulmonary microembolism resulted in an increase in lung platelet radioactivity (95.5 +/- 15.3%; n = 4), which was followed by an exponential washout (half-life = 115 +/- 4 min). Platelet uptake in the lungs was more sustained after prior fibrinolytic inhibition with tranexamic acid (half-life = 178 +/- 11 min), although the initial increase was similar (90.7 +/- 9.6%; n = 7). Prior depletion of fibrinogen with ancrod (Arvin), blunted the initial increase in lung platelet uptake after alpha-thrombin challenge (31.7 +/- 11.3%, n = 5), indicating that the effect of thrombin was markedly dependent on fibrinogen. We examined the role of circulating granulocytes, since platelets may bind to subendothelial matrix exposed after granulocyte-mediated lung vascular injury. Maximal pulmonary platelet uptake after thrombin in granulocytopenic sheep was not different from control (71.7 +/- 14.4%; n = 4). The results indicate that pulmonary microembolism results in lung platelet sequestration. Platelet uptake is not dependent on granulocyte-mediated vascular injury but requires fibrin deposition and is sustained if fibrinolysis is inhibited.
Inhomogeneity during deflation of excised canine lungs. II. Alveolar volumes
Authors: Warner D. O. , Hyatt R. E. , Rehder K.
Published: December 2017

We have previously demonstrated appreciable inhomogeneity of alveolar pressures measured by a capsule technique in excised canine lobes deflated at submaximal flows (J. Appl. Physiol. 65: 1757-1765, 1988). We further analyzed the results of these experiments by estimating alveolar volumes (VA) and regional flows from regional transpulmonary pressures, assuming that regional pressure-volume relationships were homogeneous. Deflation at submaximal flows of lungs suspended in air caused significant flow-dependent inhomogeneity of VA that increased as lung volume decreased. Immersion of lungs in stable foams that simulated the gradient of pleural pressure modified the pattern of emptying, but not always to a gravity-dependent sequence. Limitation of regional expiratory flow was often asynchronous during both air suspension and foam immersion. There was no evidence of a common regional flow-volume curve. Submaximal deflation is a complex heterogeneous process, with the interregional pattern of emptying determined by the interaction of factors that are both intrinsic and extrinsic to the lungs.
Synergism of cortisol and thyrotropin-releasing hormone in lung maturation in fetal sheep
Authors: Liggins G. C. , Schellenberg J. C. , Manzai M. , Kitterman J. A. , Lee C. C.
Published: December 2017

The effects of fetal infusions of cortisol and thyrotropin-releasing hormone (TRH) singly and together on pressure-volume relationships and saturated phosphatidylcholine (SPC) concentrations in the lungs were studied in 28 fetal sheep delivered at 128 days of gestation. Four groups each of 7 fetuses were infused with either saline (for 156 h), TRH (25 micrograms/h in 60-s pulses for 156 h), TRH (for 156 h) combined with cortisol (1 mg/h for 84 h), or cortisol (for 84 h). Cortisol had no effect on SPC concentrations, whereas both TRH and cortisol plus TRH increased the concentration of SPC in lavage fluid but not lung tissue. Neither cortisol nor TRH significantly affected lung distensibility [V40; 0.64 +/- 0.04 and 0.57 +/- 0.10 (SE) ml/g, respectively, vs. 0.41 +/- 0.03 ml/g in controls] or stability (V5; 0.24 +/- 0.01 and 0.35 +/- 0.07 ml/g vs. 0.24 +/- 0.03 ml/g), whereas treatment with a combination of the two hormones was associated with a fourfold increase in V40 (1.70 +/- 0.16 ml/g) and V5 (1.03 +/- 0.15 ml/g). Since raised concentrations of cortisol, triiodothyronine, and estradiol-17 beta (treatment with cortisol) had no effect on V40 and V5, whereas similar hormonal changes associated with elevated prolactin levels (treatment with cortisol plus TRH) had marked effects, we conclude that prolactin plays an essential part in the synergism of cortisol and TRH.
Histamine tachyphylaxis in canine airways despite prostaglandin synthesis inhibition
Authors: Antol P. J. , Gunst S. J. , Hyatt R. E.
Published: December 2017

Tachyphylaxis to aerosolized histamine was studied in dogs anesthetized with thiamylal after pretreatment with prostaglandin synthesis inhibitors. Three consecutive histamine dose-response curves were obtained in nine dogs pretreated with 5 mg/kg indomethacin; two of these nine were also pretreated with 10 mg/kg indomethacin. Seven of the nine dogs were pretreated with 4 mg/kg sodium meclofenamate; four of these seven were also pretreated with 12 mg/kg. All dogs had tachyphylaxis at high concentrations of histamine regardless of inhibitor used. Pretreatment with indomethacin while the dogs were under alpha-chloralose-urethan anesthesia gave similar results. Histamine tachyphylaxis was also studied both in the presence and in the absence of indomethacin in tracheal smooth muscle strips obtained from seven additional dogs. A decrease in the median effective dose to histamine was observed in the indomethacin-treated strips, but tachyphylaxis to histamine remained. We conclude that prostaglandin synthesis inhibition does not reverse histamine tachyphylaxis either in vivo or in vitro. Thus the mechanism of histamine tachyphylaxis remains unexplained.
Effect of O2 partial pressure on the myeloperoxidase pathway of neutrophils
Authors: Davis W. B. , Husney R. M. , Wewers M. D. , Herzyk D. J. , Sagone A. L.
Published: December 2017

Neutrophils recruited to different tissues undergo respiratory burst activity at widely different PO2 levels. The present study investigated the in vitro effects of PO2 on neutrophil oxidative metabolism. When neutrophils were stimulated with either zymosan or phorbol myristate acetate (PMA) under different PO2's (0-700 Torr), hexose monophosphate shunt activity, H2O2, and hydroxyl radical (OH.) production were directly related to the level of PO2. Neutrophils functioned surprisingly well at PO2's as low as 10 Torr, where metabolic burst activity was prolonged and usually exceeded 50% of maximal values. The production of neutrophil stable oxidants and hypochlorous acid (HOCl) by zymosan-stimulated neutrophils was also directly related to PO2. In contrast, the production of stable oxidants and HOCl by PMA-stimulated neutrophils was significantly higher at 10 Torr compared with 700 Torr. The decrease in stable oxidant production by PMA-stimulated neutrophils at elevated PO2's was explained by both increased destruction of stable oxidant products and by decreased availability of the precursor HOCl. Superoxide dismutase and the OH. scavenger benzoate partially prevented the fall in stable oxidants at elevated PO2's. Measurements of stable oxidants in PMA-stimulated supernates generated at 10 and 700 Torr correlated with the ability of these supernates to decrease the elastase inhibitory capacity of the serum antiprotease alpha 1-antitrypsin. These findings suggest that different PO2's alter the magnitude and pattern of neutrophil oxidative metabolism.
Metabolic and circulatory responses of normoxic skeletal muscle to whole-body hypoxia
Authors: Bredle D. L. , Chapler C. K. , Cain S. M.
Published: December 2017

Whole-body hypoxia may increase peripheral O2 demand because it increases catecholamine calorigenesis, an effect attributable to beta 2-adrenoceptors. We tested these possibilities by pump-perfusing innervated hindlimbs in eight dogs with autologous blood kept normoxic by a membrane oxygenator while ventilating the animals for 40 min with 9% O2 in N2 (NOB group). Similar periods of normoxic ventilation preceded and followed the hypoxic period. A second group (n = 8, beta B) was pretreated with the specific beta 2 blocker ICI 118,551. Hindlimb O2 uptake was elevated by 25 min of hypoxia in NOB, whereas whole-body O2 uptake was reduced. Limb O2 uptake remained elevated in recovery, but all effects on limb O2 uptake were absent in beta B. Hindlimb resistance and perfusion pressure increased in hypoxia in both groups, and there was little evidence of local escape from reflex vasoconstriction. These results clearly indicated that global hypoxia increased O2 demand in muscle when the local O2 supply was not limited and that beta 2-receptors were necessary for this response. Autoregulatory escape of limb muscle blood flow from centrally mediated vasoconstriction during whole-body hypoxia was also shown to be practically nil, if normoxia was maintained in the limb.
Phorbol myristate acetate-induced injury of isolated perfused rat lungs: neutrophil dependence
Authors: Perry M. , Taylor A. E.
Published: December 2017

he effect of leukocyte depletion on acute lung injury produced by intravenous or intratracheal phorbol myristate acetate (PMA) administration was studied in isolated perfused rat lungs. Vascular endothelial permeability was assessed by use of the capillary filtration coefficient (Kf,c). A predicted pulmonary capillary pressure (Ppc,p) was calculated from measurements of postcapillary resistances. These parameters were measured before and 90 min after the administration of PMA, either intratracheally or intravascularly. When blood elements were present both intratracheal and intravascular PMA caused an increased Kf,c [0.27 +/- 0.02 vs. 0.99 +/- 0.22 and 0.25 +/- 0.05 vs. 0.64 +/- 0.15 (SE) ml.min-1.cmH2O-1.100 g-1, respectively; P less than 0.05] and an increased Ppc,p (8.3 +/- 0.4 vs. 74.7 +/- 18.3 and 8.7 +/- 0.8 vs. 74.2 +/- 25.1 cmH2O, respectively; P less than 0.05). Removal of circulating leukocytes abolished the increased Kf,c when PMA was given intratracheally (0.35 +/- 0.06 vs. 0.23 +/- 0.07 ml.min-1.cmH2O-1.100 g-1) or intravascularly (0.39 +/- 0.07 vs. 0.33 +/- 0.07 ml.min-1.cmH2O-1.100 g-1). In the absence of neutrophils, Ppc,p slightly increased with intratracheal PMA, from 6.9 +/- 0.5 to 10.5 +/- 1.1 cmH2O (P less than 0.05), but was unchanged at 90 min with intravascular PMA. Depletion of circulating neutrophils with an antineutrophil serum failed to block the Kf,c change with intratracheal PMA (from 0.24 +/- 0.03 to 0.42 +/- 0.09 ml.min-1.cmH2O-1.100 g-1; P less than 0.05). Ppc,p also increased from 6.9 +/- 0.6 to 19.8 +/- 6.7 cmH2O (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Pulmonary blood flow distribution after lobar oleic acid injury: a PET study
Authors: Velazquez M. , Schuster D. P.
Published: December 2017

We evaluated the importance of hypoxic vasoconstriction as a mechanism for pulmonary blood flow reduction during unilobar oleic acid lung injury in dogs. Pulmonary blood flow (PBF) and lung water were measured with positron emission tomography. Data from the injured left (LCL) and right (RCL) caudal lobes were compared in 23 dogs. Six dogs were used to demonstrate that endotoxin (15 micrograms/kg) prevents changes in regional PBF during selective hypoxic ventilation of the LCL. In 17 dogs, oleic acid (OA, 0.015 ml/kg) was injected into the LCL through a balloon-wedged pulmonary arterial catheter. Five dogs received OA only (control group), eight received endotoxin (15 mcg/kg) before OA was administered (endotoxin group), and four were treated with prostaglandin E1 (PGE1) after OA (PGE1 group). The base-line left-to-right PBF ratio (LCL/RCL PBF) was 1.01 +/- 0.11 (SD) for the control group and 1.07 +/- 0.16 for the PGE1 group. One minute after OA, LCL/RCL PBF feel significantly (0.32 +/- 0.15 and 0.32 +/- 0.13 for the control and PGE1 groups, respectively) before any significant increase in lung water was detected. In all 17 dogs that received OA, the LCL/RCL PBF remained severely reduced 60 min after OA compared with base-line values (0.41 +/- 0.15, 0.49 +/- 0.06, and 0.26 +/- 0.13 for the control, PGF1, and endotoxin groups, respectively) despite treatment with endotoxin or PGE1. Lung water measurements obtained 60 min after OA increased significantly (P less than 0.05) in the injured lobe (LCL) but not in the normal lobe (RCL) in all dog groups, whereas PBF to the LCL remained significantly reduced.(ABSTRACT TRUNCATED AT 250 WORDS)
Altered artery mechanics and structure in monocrotaline pulmonary hypertension
Authors: Langleben D. , Szarek J. L. , Coflesky J. T. , Jones R. C. , Reid L. M. , Evans J. N.
Published: December 2017

Pulmonary hypertension in rats, induced by an injection of monocrotaline, is associated with changes in the wall structure of the pulmonary arterial bed. We have studied the effects of this remodeling on mechanical properties of cylindrical pulmonary artery segments from rats 21 days after monocrotaline (MCT) injection. Resting and active (KCl induced) circumference-tension relationships were established for segments of extrapulmonary and intrapulmonary arteries isolated from the hilum and the fifth lateral branch from the axial pathway (all preacinar). The thicknesses of the vessel wall, the media, and adventitia were measured at several positions around the circumference of the artery by computerized analysis of histological cross sections of the segments fixed at a standard circumference. Resting and active stress were also calculated. The study shows that active circumferential tension and active stress are reduced in vessels from MCT-treated rats. Based on our findings, it is unlikely that altered contractile function of preacinar arteries contributes significantly to the increased vascular resistance seen in this model.
Characteristics and functional significance of canine abdominal muscles
Authors: Farkas G. A. , Rochester D. F.
Published: December 2017

To assess the characteristics and function of the muscles of the anterolateral abdominal wall, we have examined the isometric contractile properties of bundles of canine rectus abdominis (RA) and external oblique (EO) muscles. In addition, we have related the lengths of these muscles measured sonometrically in vivo at supine functional residual capacity (FRC) to in vitro optimal force-producing length (Lo). We also investigated the action of the abdominal muscles on the displacement of costal and crural diaphragm. We found that 1) contraction time of RA was longer and that the RA developed greater force than the EO at submaximal stimulation frequencies; 2) maximal tetanic force and the active length-tension curves were similar in both abdominal muscles; 3) on passive stretch, the compliance of the RA was one-third that of the EO; 4) at supine FRC, the EO is operating at 83% of Lo, whereas the RA is operating at 105% of Lo; 5) stimulation of either RA or EO (abdominal pressure of 15 cmH2O) lengthened the costal and crural diaphragm toward their Lo values, with greater crural excursion occurring than costal. We conclude that the RA is well suited for restraining the abdominal viscera in prone quadrupeds, whereas the EO is better designed to assist expiration. Stimulation of both muscles improves in situ diaphragmatic operating length.
Role of triangularis sterni during coughing and sneezing in dogs
Authors: van Lunteren E. , Haxhiu M. A. , Cherniack N. S. , Arnold J. S.
Published: December 2017

Studies in mammals have found that during breathing the triangularis sterni (TS) muscle regulates expiratory airflow and the end-expiratory position of the rib cage and furthermore that the respiratory activity of this muscle is influenced by a variety of chemical and mechanical stimuli. To assess the role of the TS during coughing and sneezing, electromyograms (EMGs) recorded from the TS were compared with EMGs of the transversus abdominis (TA) in eight pentobarbital-anesthetized dogs. During coughing induced by mechanically stimulating the trachea or larynx (n = 7 dogs), peak EMGs increased from 23 +/- 2 to 74 +/- 5 U (P less than 0.00002) for the TS and from 21 +/- 6 to 66 +/- 4 U (P less than 0.0002) for the TA. During sneezing induced by mechanically stimulating the nasal mucosa (n = 3 dogs), peak EMG of the TS increased from 10 +/- 3 to 66 +/- 7 U (P less than 0.005) and peak EMG of the TA increased from 10 +/- 2 to 73 +/- 7 U (P less than 0.02). For both muscles the shape of the EMG changed to an early peaking form during coughs and sneezes. Peak expiratory airflow during coughs of different intensity correlated more closely with peak TS EMG in three dogs and with peak TA EMG in four dogs; peak expiratory airflow during sneezes of different intensity correlated more closely with peak TS than TA EMG in all three animals. These results suggest that the TS is actively recruited during coughing and sneezing and that different neuromuscular strategies may be utilized to augment expiratory airflow.
Hypoxic contractile response in isolated human pulmonary artery: role of calcium ion
Authors: Hoshino Y. , Obara H. , Kusunoki M. , Fujii Y. , Iwai S.
Published: December 2017

The mechanism for hypoxic pulmonary vasoconstriction (HPVC) was investigated in human pulmonary arterial strips. Hypoxia in the presence of histamine (10(-6) M) caused marked pulmonary arterial contraction, which was reversed by O2. The hypoxic contraction in the presence of histamine was inhibited by diphenhydramine, but not by cimetidine. The hypoxic histamine-mediated contraction was attenuated but still present in the absence of extracellular Ca2+, or by the inhibitors of voltage-dependent Ca2+ influx. However, it was inhibited significantly by a further depletion of intracellular Ca2+, or by HA 1004, an intracellular calcium antagonist. A low concentration (10(-7) M) of a calcium ionophore, A23187, enhanced the hypoxic contraction in the presence of histamine, whereas procaine completely inhibited it. W-7, a calmodulin inhibitor, significantly decreased the hypoxic histamine-mediated contraction, but 12-O-tetradecanoylphorbol-13-acetate (TPA), a C-kinase promotor, had no effect. The hypoxic contractile response was also observed in the presence of both A23187 and KCl instead of histamine, but the hypoxia-induced contraction with KCl alone was much smaller than that. These results indicate that hypoxia in the presence of certain other vasoactive agents has a potent contractile effect on the human pulmonary artery and that the response is dependent on Ca2+. Enhancement of both Ca2+ influx and Ca2+ release from intracellular storage sites by hypoxia, which interacts with calmodulin, were suggested to be involved in the mechanism of HPVC.
VIP augments cholinergic-induced glycoconjugate secretion in tracheal submucosal glands
Authors: Shimura S. , Sasaki T. , Ikeda K. , Sasaki H. , Takishima T.
Published: December 2017

Using isolated submucosal glands from feline trachea, we examined the effect of vasoactive intestinal peptide (VIP) on mucus glycoprotein secretion and glandular contraction by measuring released radiolabeled glycoconjugates and induced tension, respectively. VIP (10(-10) to 10(-6) M) produced a dose-dependent increase in [3H]glycoconjugate release of up to 300% of controls, which was inhibited by VIP antiserum and not inhibited by atropine, propranolol, or phentolamine. VIP at a low concentration (10(-9) M), which did not produce any significant increases over controls, produced a 2.4- to 5-fold augmentation of the glycoconjugate release induced by 10(-9) to 10(-7) M methacholine (MCh). Atropine or VIP antiserum abolished the augmentation. VIP did not produce any alteration in isoproterenol- or phenylephrine-evoked glycoconjugate secretion. VIP (up to 10(-5) M) did not produce any alteration in the tension, even when the gland had contracted with MCh, or any augmentation of contraction induced by MCh (10(-9) to 10(-7) M). These results indicate that VIP induces mucus glycoprotein release from secretory cells and also that it potentiates the secretion induced by cholinergic stimulation.
Regulation of hepatic glucose production in running rats studied by glucose infusion
Authors: Vissing J. , Sonne B. , Galbo H.
Published: December 2017

The importance of metabolic feedback regulation vs. feedforward regulation of hepatic glucose production (HGP) during exercise was investigated in rats by infusing glucose intravenously from the onset of running. Glucose infusion equaled the average exercise-induced increase from basal to steady state in HGP found in saline-infused control rats. Rats were studied at two work loads, running at 21 (series I) or 18 m/min (series II) for 35 min. Glucose turnover was measured by means of an intravenous [3H]glucose infusion. HGP was suppressed by glucose infusion corresponding to the infused amount of glucose in both series, except for late in exercise in series I, where HGP plus infused glucose tended to exceed HGP in saline-infused rats (P less than 0.10). Muscle glycogenolysis and fat metabolism were similar in both groups in the two series. Plasma glucose was never elevated, whereas insulin was, in glucose- vs. saline-infused rats of both series. Plasma catecholamines were lower in glucose- compared with saline-infused rats in series II. In conclusion, HGP is very sensitive to metabolic feedback inhibition at low exercise intensities. Feedforward control of HGP may play a role at higher work loads (series I). Exogenously supplied glucose, in moderate amounts, may replace HGP specifically without concomitant changes in mobilization of other substrates.
Comparative permeability of canine visceral and parietal pleura
Authors: Payne D. K. , Kinasewitz G. T. , Gonzalez E.
Published: December 2017

To determine the permeability of canine pleural mesothelium, visceral and intercostal parietal pleura from mongrel dogs was carefully stripped from the underlying tissue and mounted as a planar sheet in a Ussing-type chamber. The hydraulic conductivity (Lp) was determined from the rate of volume flux in response to hydrostatic pressure gradients applied to either the mucosal or serosal surface of the pleural membrane. The diffusional permeability (Pd) of radiolabeled water, sucrose, inulin, and albumin was determined under equilibrium conditions from the unidirectional tracer flux. The Lp of the visceral pleura was 0.39 +/- 0.032 (SE) X 10(-4) ml.s-1.cmH2O-1.cm-2 and that Lp of parietal pleura was 1.93 +/- 0.93 X 10(-4) ml.s-1.cmH2O-1.cm-2 (P less than 0.001). The Pd of the visceral pleura ranged from 12.21 +/- 0.45 X 10(-4) cm/s for 3H2O to 0.34 +/- 0.03 X 10(-4) cm/s for [3H]albumin. The Pd of the parietal pleura for water and sucrose was similar to that of the visceral membrane, whereas its Pd for the larger inulin and albumin molecules was greater than that of visceral pleura (P less than 0.01). A spontaneous potential difference could not be detected across either membrane. The relatively higher parietal pleural Lp and Pd for larger solutes is probably due to the presence of stomata in this membrane. These results indicate that both the parietal and the visceral pleura are extremely permeable tissues which offer little resistance to water and solute flux.
Abdominal muscle activity during speech production
Authors: Hoit J. D. , Plassman B. L. , Lansing R. W. , Hixon T. J.
Published: December 2017

Abdominal muscle activity was investigated during resting tidal breathing and speech production in upright and supine body positions in five male and five female young adult subjects. Results showed that patterns of abdominal electromyographic (EMG) activity were highly dependent on body position. Data for resting tidal breathing resembled those of previous investigations and revealed one sex-related finding. Data for speech production indicated that the lateral region of the abdomen was highly active in the upright position and occasionally active in the supine position. In the upright position, lateral EMG levels during speech production were characterized by generally higher levels in the lower than upper lateral sites and were almost always higher than during resting tidal breathing. In the supine position, EMG levels during speech production occasionally exceeded those associated with resting tidal breathing but were substantially lower than those associated with upright speech production. Abdominal EMG activity was most prevalent during loud speech production and during speech produced at low lung volumes. Findings are discussed in relation to current knowledge of respiratory mechanics and neural control.
Targeted resistive ventilatory muscle training in chronic obstructive pulmonary disease
Authors: Belman M. J. , Shadmehr R.
Published: December 2017

To overcome the problem of altered breathing strategy during resistive ventilatory muscle training (VMT), we used a single-orifice inspiratory resistance together with a target feedback device (TFD) in patients with chronic obstructive pulmonary disease (COPD). In a preliminary study (study A), we showed that the resistance plus TFD was effective in controlling breathing strategy. We subsequently used the resistor plus TFD in a 5-wk study (study B) of VMT in 17 COPD patients who were randomized into high-intensity (HI) and low-intensity (LI) training groups. Compared with the LI group, the HI group showed significant increases in static maximal inspiratory pressure (21.3 vs. 5.0 cmH2O), maximal sustained ventilatory capacity (MSVC, 3.2 vs -0.1 l/min, sustained maximal mouth pressure (12.1 vs. 0.6 cmH2O), mean mouth pressure (6.9 vs. 3.9 cmH2O), peak inspiratory flow rate (12.3 vs. 4.0 l/min), and maximal sustained work rate (12.2 vs. 4.2 cmH2O.l-1.min-1). We conclude that targeted VMT with control of breathing strategy improves both ventilatory muscle strength and endurance.
Relationship of diaphragmatic contractility to diaphragmatic blood flow in newborn lambs
Authors: Nichols D. G. , Howell S. , Massik J. , Koehler R. C. , Gleason C. A. , Buck J. R. , Fitzgerald R. S. , Traystman R. J. , Robotham J. L.
Published: December 2017

We determined the relationship of diaphragmatic contraction rate to diaphragmatic blood flow (Qdi), metabolism, and contractility in nine open-chested mechanically ventilated newborn lambs. The diaphragm was paced for 15 min at slow (20/min) and fast (100/min) contraction rates each followed by a 30-min rest period. There was a mild reduction in transdiaphragmatic pressure (Pdi) during the slow contraction period accompanied by a shift to the right of the curve relating stimulation frequency (10–100 Hz) to Pdi. Pdi returned to control at the start of the fast contraction period, but then fell by 30% within 2 min with continued fast contraction rates. The frequency-Pdi curve was significantly shifted to the right. Qdi, O2 transport, and O2 consumption increased during slow contraction and to an even greater extent during fast contraction. Fractional O2 extraction reached an apparent maximum during slow contraction. Lactate efflux from the right phrenic vein during slow contraction remained unchanged from control. During fast contraction lactate efflux rose proportionately more than did O2 consumption. We conclude that the energy demands at fast rates of diaphragmatic contraction in newborn lambs cannot be met by aerobic metabolism alone despite increasing O2 transport to the diaphragm.
Role of costal and crural diaphragm and parasternal intercostals during coughing in cats
Authors: van Lunteren E. , Daniels R. , Deal E. C. , Haxhiu M. A.
Published: December 2017

The inspiratory phase of coughs often consists of large inspired volumes and increased motor discharge to the costal diaphragm. Furthermore, diaphragm electrical activity may persist into the early expiratory portion of coughs. To examine the role of other inspiratory muscles during coughing, electromyograms (EMG) recorded from the crural diaphragm (Dcr) and parasternal intercostal (PSIC) muscles were compared to EMG of the costal diaphragm (Dco) in anesthetized cats. Tracheal or laryngeal stimulation typically produced a series of coughs, with variable increases in peak inspiratory EMGs of all three muscles. On average, peak inspiratory EMG of Dco increased to 346 +/- 60% of control (P less than 0.001), Dcr to 514 +/- 82% of control (P less than 0.0002), and PSIC to 574 +/- 61% of control (P less than 0.0005). Augmentations of Dcr and PSIC EMG were both significantly greater than of Dco EMG (P less than 0.05 and P less than 0.002, respectively). In most animals, EMG of Dco correlated significantly with EMG of Dcr and of PSIC during different size coughs. Electrical activity of all three muscles persisted into the expiratory portions of many (but not all) coughs. The duration of expiratory activity lasted on average 0.17 +/- 0.03 s for Dco, 0.25 +/- 0.06 s for Dcr, and 0.31 +/- 0.09 s for PSIC. These results suggest that multiple respiratory muscles are recruited during inspiration of coughs, and that the persistence of electrical activity into expiration of coughs is not unique to the costal diaphragm.
Effect of exercise on the development of osteoporosis in adult rats
Authors: Myburgh K. H. , Noakes T. D. , Roodt M. , Hough F. S.
Published: December 2017

The role of moderate exercise in the prevention of high-turnover osteoporosis was investigated by the use of an animal model. The effect of chronic training on gravimetric, mineral, physical, and histological parameters of normal bone was also examined. Fifty-six adult female Long-Evans rats were divided into four groups: sedentary (C) and exercising controls (E) and sedentary (O) and exercising osteoporotics (EO). Exercising animals ran 4 h/wk for 1 yr. Two percent NH4Cl added to drinking water induced osteoporosis as shown by significantly lower femoral density and breaking strength and histomorphometrically quantified tibial trabecular bone volume but a normal mineral-to-matrix ratio in the O rats. The development of high-turnover osteoporosis in O rats was confirmed by significantly higher alkaline phosphatase activity (P less than 0.05), urinary hydroxyproline content (P less than 0.01), resorption surfaces (P less than 0.01), and histological parameters of bone formation (P less than 0.01). Exercise prevented all these biochemical, biophysical, and histological abnormalities in the EO group. Exercise had no influence on the density of normal femurs but tended to increase their breaking strength (by 11%) compared with femurs of C rats (P = 0.11).
Does acute hypoxemia blunt sympathetic activity in hyperthermia?
Authors: Rowell L. B. , Brengelmann G. L. , Savage M. V. , Freund P. R.
Published: December 2017

Sympathetic alpha-adrenergic function is depressed by hypoxemia per se; does addition of another sympathoexcitatory stimulus elicit normal responses in other sympathetic effector pathways? We activated by hyperthermia four sympathetic pathways: alpha-adrenergic [norepinephrine (NE) release], beta-adrenergic [plasma renin activity (PRA)], cholinergic (sweating), and peptidergic (active vasodilation). In the first test, five normothermic men were exposed to hypoxemia for 10 min (control), then hypoxemia plus heat for 30 min, and then heat with normoxia for 8–10 min over a continuous 48- to 50-min period. Heating was controlled with a water-perfused suit. Time courses and magnitudes of heat-induced increments in body temperature, forearm blood flow, and sweat rate were normal during hypoxemia and unaffected by switching to normoxia. Hypoxemia exaggerated increases in plasma NE, epinephrine, PRA, and heart rate but had no additional effects on blood pressure. In a second 50-min test (2 men) with normoxic control (10 min), heating plus normoxia (20 min), and heating plus hypoxemia (20 min), effects of hypoxemia on all variables were as in the first test. Thus, acute moderate hypoxemia did not blunt active cutaneous vasodilation or sweating and exaggerated increases in catecholamines and heart rate, indicating maintained peripheral autonomic function.
Cardiovascular response to cycle exercise during and after pregnancy
Authors: Sady S. P. , Carpenter M. W. , Thompson P. D. , Sady M. A. , Haydon B. , Coustan D. R.
Published: December 2017

Our purpose was to determine if pregnancy alters the cardiovascular response to exercise. Thirty-nine women [29 +/- 4 (SD) yr], performed submaximal and maximal exercise cycle ergometry during pregnancy (antepartum, AP, 26 +/- 3 wk of gestation) and postpartum (PP, 8 +/- 2 wk). Neither maximal O2 uptake (VO2max) nor maximal heart rate (HR) was different AP and PP (VO2 = 1.91 +/- 0.32 and 1.83 +/- 0.31 l/min; HR = 182 +/- 8 and 184 +/- 7 beats/min, P greater than 0.05 for both). Cardiac output (Q, acetylene rebreathing technique) averaged 2.2 to 2.8 l/min higher AP (P less than 0.01) at rest and at each exercise work load. Increases in both HR and stroke volume (SV) contributed to the elevated Q at the lower exercise work loads, whereas an increased SV was primarily responsible for the higher Q at higher levels. The slope of the Q vs. VO2 relationship was not different AP and PP (6.15 +/- 1.32 and 6.18 +/- 1.34 l/min Q/l/min VO2, P greater than 0.05). In contrast, the arteriovenous O2 difference (a-vO2 difference) was lower at each exercise work load AP, suggesting that the higher Q AP was distributed to nonexercising vascular beds. We conclude that Q is greater and a-vO2 difference is less at all levels of exercise in pregnant subjects than in the same women postpartum but that the coupling of the increase in Q to the increase in systemic O2 demand (VO2) is not different.(ABSTRACT TRUNCATED AT 250 WORDS)
Tritiated water as a measure of body water in immature rats growing at different rates
Authors: Sheng H. P. , Huggins R. A.
Published: December 2017

Rats were reared from birth in litters of 4, 10, and 16 to achieve different growth rates. Pups in the litters of 16 had no access to rat chow until days 21–28, when chow was made available to one of the litters to induce catch-up growth. Total body water was estimated by tritiated water (TBWHTO) on days 7, 14, 21, and 28 and then calculated from desiccation (TBWdes). TBWHTO was consistently larger than TBWdes for all groups. Differences were 10.9–16.9% on day 7 and 3.7–6.4% on day 28. On day 28, percent difference was higher in the slower-growing than the faster-growing groups. Nonaqueous hydrogen exchange was determined from tritium activity in the dried carcass. Less than 1% of the injected tritium exchanged with nonaqueous hydrogen during the equilibration period. Thus differences between TBWHTO and TBWdes in the younger animals could not be accounted for by nonaqueous hydrogen exchange but may have resulted from a larger loss of injected tritium, possibly in insensible water.
Calcitonin and CGRP block bombesin- and substance P-induced increases in airway tone
Authors: Gatto C. , Lussky R. C. , Erickson L. W. , Berg K. J. , Wobken J. D. , Johnson D. E.
Published: December 2017

Calcitonin gene-related peptide (CGRP) and calcitonin (C) are two peptides that are cocontained and probably coreleased with the potent bronchocontrictors, bombesin (B) and substance P (SP), within the lung. Although CGRP and C have a wide intrapulmonary distribution, their actions have not been well defined. By the use of a computerized lung mechanics analyzer, changes in response to 10-min infusions of these agents were measured in spontaneously breathing, anesthetized guinea pigs. Infusion of 0.3 nmol.kg-1.min-1 CGRP and 2 nmol.kg-1.min-1 C caused little change in lung mechanics. Infusion of 0.06 nmol.kg-1.min-1 B and 0.3 nmol.kg-1.min-1 SP caused a marked increase in inspiratory, expiratory, and total pulmonary resistance (RT), from base-line values (P less than 0.02), with a maximal effect at 10 min postinfusion (PI) [RT = 326 +/- 20% (SE) (B), 490 +/- 73% (SP)]. Coinfusion of C or CGRP with B or SP at the above concentrations caused a marked reduction in SP - [RT = 189 +/- 28% (C), 142 +/- 16% (CGRP) at 10 min PI] and B - [RT = 157 +/- 18% (C), 158 +/- 10% (CGRP) at 10 min PI] induced changes in resistance (P less than 0.015). The mode of action of C and CGRP is unknown, but these peptides may antagonize the effects of B and SP via autonomic pathways by interfering with B- or SP-induced changes in intracellular calcium concentrations or by increasing intracellular cAMP levels by binding to specific cellular receptors linked to adenylate cyclase.
Polyethylene glycol-attached antioxidant enzymes decrease pulmonary oxygen toxicity in rats
Authors: White C. W. , Jackson J. H. , Abuchowski A. , Kazo G. M. , Mimmack R. F. , Berger E. M. , Freeman B. A. , McCord J. M. , Repine J. E.
Published: December 2017

When exposed continuously to hyperoxia (100% O2, 760 Torr barometric pressure), rats pretreated with polyethylene glycol (PEG)-attached superoxide dismutase and catalase (PEG-SOD + PEG-CAT) lived longer (79.1 + 7.6 h) than rats pretreated with saline (60.7 +/- 2.1 h) or PEG-inactivated-SOD + PEG-inactivated-CAT (62.3 +/- 1.6 h). Rats pretreated with PEG-SOD + PEG-CAT also had less hyperoxia-induced acute oxidative edematous lung injury, as assessed by increases in lung oxidized glutathione (GSSG) contents, pleural effusions, and lung lavage albumin concentrations than saline-pretreated rats. Rats pretreated with the long-lived conjugates PEG-inactivated-SOD + PEG-inactivated-CAT or PEG-albumin also had decreased acute oxidative edematous lung injury compared with rats pretreated with PEG, SOD + CAT + PEG, SOD + CAT, or saline. In vitro studies suggested that PEG itself may have contributed to protection by scavenging hydroxyl radical (.OH) but not superoxide (O2-.) or H2O2. Compared with more effective endogenous (via preexposure to hypoxia) or exogenous (via liposomes) means for increasing lung antioxidant enzymes, PEG enzymes are less protective against lung injury from continuous hyperoxia.
Muscle energetics during prolonged cycling after exercise hypervolemia
Authors: Green H. J. , Jones L. L. , Houston M. E. , Ball-Burnett M. E. , Farrance B. W.
Published: December 2017

This study examined the question of whether increases in plasma volume (hypervolemia) induced through exercise affect muscle substrate utilization and muscle bioenergetics during prolonged heavy effort. Six untrained males (19–24 yr) were studied before and after 3 consecutive days of cycling (2 h/day at 65% of peak O2 consumption) performed in a cool environment (22–23 degrees C, 25–35% relative humidity). This protocol resulted in a 21.2% increase in plasma volume (P less than 0.05). During exercise no difference was found in the blood concentrations of glucose, lactate, and plasma free fatty acids at either 30, 60, 90, or 120 min of exercise before and after the hypervolemia. In contrast, blood alanine was higher (P less than 0.05) during both rest and exercise with hypervolemia. Measurement of muscle samples extracted by biopsy from the vastus lateralis muscle at rest and at 60 and 120 min of exercise indicated no effect of training on high-energy phosphate metabolism (ATP, ADP, creatine phosphate, creatine) or on selected glycolytic intermediate concentrations (glucose 1-phosphate, glucose 6-phosphate, fructose 6-phosphate, lactate). In contrast, training resulted in higher (P less than 0.05) muscle glucose and muscle glycogen concentrations. These changes were accompanied by blunting of the exercise-induced increase (P less than 0.05) in both blood epinephrine and norepinephrine concentrations. Plasma glucagon and serum insulin were not affected by the training. The results indicate that exercise-induced hypervolemia did not alter muscle energy homeostasis. The reduction in muscle glycogen utilization appears to be an early adaptive response to training mediated either by an increase in blood glucose utilization or a decrease in anaerobic glycolysis.