bluuebunny/crossref_metadata_2025 huggingface dataset:
Hemodynamic effects of synchronous high-frequency jet ventilation during acute hypovolemia
Authors: Matuschak G. M. , Pinsky M. R. , Klain M.
Published: December 2017

We studied the effects of synchronous cardiac cycle-specific high-frequency jet ventilation (HFJV) in pentobarbital-anesthetized, splenectomized, closed-chest dogs to test the hypothesis that phasic inspiratory increases in intrathoracic pressure (ITP) selectively timed to specific periods of the cardiac cycle have different hemodynamic effects during both hypovolemia (acute hemorrhage, 20 ml/kg) and neurogenic vasomotor shock (hexamethonium, 10 mg/kg) than those observed during normovolemic control conditions. Ventricular stroke volumes (SV) were measured by electromagnetic flow probes. The influence of changes in venous return (VR) on the subsequent hemodynamic response to synchronous HFJV was analyzed using instantaneous VR curves (M. R. Pinsky, J. Appl. Physiol. 56:765–771, 1984). During hemorrhage the VR curve was shifted leftward with concomitant reductions in apneic SV (15.4 +/- 3.8 to 11.2 +/- 3.6 ml, mean +/- SD), (P less than 0.01) that were accentuated by HFJV (P less than 0.01), except when the phasic inspiratory increases in ITP during HFJV were timed to occur during late diastole (-4% apneic SV, NS). SV was greater with late diastolic pulses than with other timed synchronous ITP pulses during hypovolemia (P less than 0.01). During ganglionic blockade, arterial pressure decreased (139 +/- 14 to 76 +/- 18 Torr, P less than 0.001), but VR was preserved at control levels, and no significant cardiac cycle-specific HFJV effects occurred. We conclude that SV reductions associated with positive-pressure ventilation during acute hypovolemia are minimized by HFJV synchronized to late diastole but that this effect is preload dependent.
Bronchial responsiveness to nonantigenic bronchoconstrictors in awake sheep
Authors: Snapper J. R. , Lefferts P. L. , Stecenko A. A. , Hinson J. M. , Dyer E. L.
Published: December 2017

The experiments were designed to further characterize pulmonary responsiveness to nonantigenic aerosol bronchoconstrictors in unanesthetized sheep. The distribution of aerosol histamine responsiveness was described among 55 sheep. Within day reproducibility of aerosol histamine (n = 18) and carbachol (n = 8) responsiveness was studied and aerosol histamine and carbachol responsiveness were compared (n = 9). The effects of cyclooxygenase inhibition with meclofenamate (n = 7) and ibuprofen (n = 8) on pulmonary responsiveness to aerosol histamine was studied as was the effect of ibuprofen (n = 6) on pulmonary responsiveness to aerosol carbachol. A log normal unimodal distribution of pulmonary responsiveness to aerosol histamine was described. Within day pulmonary responsiveness to aerosol histamine was highly reproducible while pulmonary responsiveness to aerosol carbachol decreased slightly, but not significantly, on the second challenge. Pulmonary responsiveness to aerosol histamine correlated with pulmonary responsiveness to aerosol carbachol (r = 0.85, P less than 0.05). Meclofenamate did not significantly attenuate pulmonary responsiveness to aerosol histamine. Ibuprofen attenuated pulmonary responsiveness to aerosol histamine (P less than 0.05) but not to aerosol carbachol. These experiments supply basic information related to pulmonary responsiveness to nonantigenic bronchoconstrictors in awake sheep.
Total body water-to-lean body mass ratio in baboons (Papio sp.) of varying adiposity
Authors: Lewis D. S. , Bertrand H. A. , Masoro E. J.
Published: December 2017

Total body water (TBW), lean body mass (LBM), and triglyceride mass were measured in 23 5-yr-old baboons (13 females and 10 males). Male baboons weighed more, had more LBM, more TBW, and contained less triglyceride mass per unit body weight than female baboons. Among all baboons, triglyceride mass per unit body weight ranged from 2.4 to 33.5%. The ratio TBW:LBM ranged from 0.70 to 0.92, increasing (r = 0.98) with increased body triglyceride content (both percent and absolute mass) in both male and female baboons. However, the water content per unit weight of tissues free of fat cells (liver, lungs, kidneys, central nervous system, eyes, tongue) was nearly constant at 0.73 +/- 0.02. The increase in TBW:LBM is more than can be expected from the water in the increased adipose tissue mass. We conclude that TBW:LBM is not constant but is influenced by body triglyceride content in baboons.
Rapid shallow breathing evoked by capsaicin from isolated pulmonary circulation
Authors: Schertel E. R. , Adams L. , Schneider D. A. , Smith K. S. , Green J. F.
Published: December 2017

Recently Green et al. (J. Appl. Physiol. 57:562–567, 1984) reported that pulmonary C-fibers initiate the prompt apnea evoked by pulmonary arterial injections of capsaicin; however, their role in the subsequent rapid shallow breathing of the pulmonary chemoreflex is still in dispute. To determine whether this reflex tachypnea is triggered by pulmonary C-fibers rather than by afferents further downstream, we separately perfused the pulmonary and systemic circulations in dogs anesthetized with either halothane or alpha-chloralose as the lungs were ventilated with a servo-controlled ventilator driven by phrenic nerve activity. Injection of capsaicin (10 micrograms/kg) into the pulmonary artery of the isolated pulmonary circulation evoked an immediate apnea followed by rapid shallow breathing. Injection of the same dose of capsaicin into the left atrium of the isolated pulmonary circulation had no effect. By contrast, when capsaicin was administered at a slower rate into the pulmonary artery (10–20 micrograms X kg-1 X min-1) rapid shallow breathing occurred but without apnea. Our results are consistent with the hypothesis that in spontaneously breathing animals, stimulation of pulmonary C-fibers can evoke rapid shallow breathing.
Diethyl pyrocarbonate (an imidazole binding substance) inhibits rostral VLM CO2 sensitivity
Authors: Nattie E. E.
Published: December 2017

Diethyl pyrocarbonate (DEPC) has been useful in vitro as an agent relatively specific for binding to imidazole of histidine. Administered via the cisterna magna DEPC inhibits central chemosensitivity in conscious rabbits, supporting the alphastat hypothesis for central chemoreceptor function. In this study I have applied DEPC via 1 X 3 mm cottonoid pledgets to each of the three ventrolateral medulla (VLM) chemosensitive areas in glomectomized, vagotomized, paralyzed, and servo-ventilated alpha-chloralose-urethan-anesthetized cats. CO2 responses measured by integrated phrenic nerve output were evaluated before and after DEPC application. A dose of 40 mmol/l applied to the rostral chemosensitive area increased the CO2 threshold (5.3%) and significantly decreased (P less than 0.03; Wilcoxon sign rank test) the initial slope (-43%) and the maximum (-41%) of the CO2 response. No significant effects were observed with DEPC application in the intermediate or caudal areas. Treatment with 40 mmol/l hydroxylamine immediately after DEPC in the rostral area prevented the effects supporting the interpretation that imidazole was the reactant with DEPC. The results are consistent with the hypothesis that imidazole-histidine is involved in the mechanism of central chemoreception and indicate that only the rostral area utilizes a DEPC inhibitable mechanism.
Effect of arterial PCO2 on 2-[1-14C]deoxy-D-glucose uptake by feline cerebral arteries
Authors: Kostreva D. R. , McNeely J. , Zuperku E. J.
Published: December 2017

The effect of high and low arterial CO2 on the glucose utilization of nine major cerebral arteries was studied in cats anesthetized with pentothal using the quantitative 2-[1–14C]deoxy-D-glucose autoradiographic technique. All nine cerebral arteries from animals subjected to an arterial partial pressure of CO2 (PCO2) of 20 Torr utilized significantly more (P less than 0.025) glucose than the group subjected to an arterial PCO2 of 60 Torr. Mean relative glucose utilization of the 20-Torr PCO2 group was 105 +/- 9.5 mumol X 100g-1 X min-1 (+/- SE, n = 18) as compared with 49 +/- 6 mumol X 100g-1 X min-1 (+/- SE, n = 26) for the 60-Torr PCO2 group. This study demonstrates that blood vessels can be studied in vivo using the 2-[1-14C]deoxy-D-glucose autoradiographic technique. It also demonstrates that a physiological stimulus like CO2 can produce measurable changes in glucose utilization of cerebral arteries in vivo.
Epithelial modulation of tracheal smooth muscle response to antigenic stimulation
Authors: Frossard N. , Muller F.
Published: December 2017

The role of the epithelium has been studied in the contractile responses of rat trachea. The different modulations observed are discussed in respect to vagal components of the epithelial layer. Responses of rat trachea to immunologic stimulation are shown to be dependent on the presence of the epithelium, which prolongs the relaxation stage without affecting the contractions. This prolongation is abolished by neonatal capsaicin pretreatment, whereas substance P induces a significantly greater relaxation of serotonin-precontracted intact than deepithelialized trachea. Serotonin concentration-response curves are shifted to the right in intact preparations, which is partly reversed by neonatal capsaicin pretreatment, but a hyporeactivity of the tissue exists. A relaxing factor released by the epithelium is hypothesized, possibly dependent on substance P-ergic innervation. Muscarinic cholinergic innervation slightly modulates the contractions but not the relaxations in antigen-induced responses, independently on the presence of the epithelial layer. 4-Aminopyridine induces epithelium-dependent potentiations of contractions to antigen and to serotonin, which involves acetylcholine at one step of the reaction cascade. Epithelial-dependent contracting and relaxing factors are thus suggested in rat trachea.
Relationship between diaphragm length and abdominal dimensions
Authors: Decramer M. , Xi J. T. , Reid M. B. , Kelly S. , Macklem P. T. , Demedts M.
Published: December 2017

We examined the relationship between changes in abdominal cross-sectional area, measured by respiratory inductive plethysmography, and changes in length in the costal and crural parts of the diaphragm, measured by sonomicrometry, in nine supine, anesthetized dogs. During passive inflation, both parts of the diaphragm shortened and abdominal cross-sectional area increased. During passive deflation, both parts of the diaphragm lengthened and abdominal cross-sectional area decreased. We subsequently used the relationship between costal and crural diaphragmatic length, respectively, and abdominal cross-sectional area during passive inflation-deflation to predict the length changes in the costal and crural diaphragm during quiet breathing before and after bilateral phrenicotomy. In the intact animal the inspiratory shortening in the crural diaphragm was almost invariably greater than predicted from the relationship during passive inflation. During inspiration after phrenicotomy the crural diaphragm invariably lengthened, whereas the costal diaphragm often shortened. In general there was a good correlation between the measured and predicted length change for the crural diaphragm (r = 0.72 before and 0.79 after phrenicotomy) and a poor one for the costal diaphragm (r = 0.05 before and 0.19 after phrenicotomy).
Effects of prolonged simultaneous exposure of CD-1 mice to high pressures and inert gas narcosis
Authors: Brauer R. W. , Dutcher J. A. , Vorus W. S.
Published: December 2017

Addition of N2 to the heliox used in pressure conditioning exposures reduces or suppresses the increase in convulsion threshold pressure (Pc) as well as the change in compression rate effect resulting from pressure exposures in the absence of N2; 18 atm N2 neutralizes the effect of 80 ATA total pressure so that Pc remains at a constant level throughout the conditioning period. Since N2 habituation is much slower than pressure conditioning (t1/2 6 days vs. 12 h), this precludes mere addition of pressure and N2 effects in this situation. In contrast to Pc, anesthesia tolerance of mice exposed to 80 ATA in the presence of 18 atm N2 increases even more (25%) than at the same PN2 but at a total pressure of only 18 ATA, indicating that pressure reversal of anesthesia does not extend to the habituation events. The implications of the striking asymmetry between the effects of protracted high pressure and inert gas narcotic exposures for an understanding of the nature of the supposed IG/HP antagonism are discussed.
Hyperbaric hyperoxia reversibly inhibits erythrocyte phospholipid fatty acid turnover
Authors: Dise C. A. , Clark J. M. , Lambersten C. J. , Goodman D. B.
Published: December 2017

The present study is one component of a comprehensive investigation of oxygen tolerance of tissues and organs in normal human subjects. The focus of this study was the acylation of membrane phospholipid in situ by erythrocytes. Activation of exogenous [9,10–3H]oleic acid to acyl thioester and transesterification of the acyl thioester into phospholipid by intact human erythrocytes incubated in vitro decreased 30% after exposure of 10 human subjects to hyperbaric hyperoxia (100% O2, 3 ATA, 3.5 h). Partial recovery of activity could be detected when additional cells were obtained from these subjects and assayed in vitro 24 h after cessation of exposure. No significant change in membrane phospholipid fatty acid composition was detected under these conditions. The reduced glutathione content of intact erythrocytes increased by 15% after hyperbaric hyperoxia and remained elevated 24 h after exposure. In isolated membranes prepared from the same cells activation of [9,10–3H]oleic acid to acyl thioester and its transesterification into phospholipid did not change after hyperoxia. Since the ability of intact cells to replace oxidized fatty acids in membrane phospholipids via deacylation and reacylation in situ may be necessary for the maintenance of membrane integrity during exposure to oxidative stress, the decrease in [9,10–3H]oleic acid incorporation by human erythrocytes detected in vitro after hyperbaric hyperoxia in vivo may reflect an early event in the pathogenesis of oxygen-induced cellular injury and may be a useful index for assessment of the tolerance of tissues to hyperoxia.
Effect of resting smooth muscle length on contractile response in resistance airways
Authors: Shioya T. , Munoz N. M. , Leff A. R.
Published: December 2017

We studied the effect of resting smooth muscle length on the contractile response of the major resistance airways (generations 0–5) in 18 mongrel dogs in vivo using tantalum bronchography. Dose-response curves to 10(-10) to 10(-7) mol/kg methacholine (MCh) were generated [at functional residual capacity (FRC)] by repeated intravenous bolus administration using tantalum bronchography after each dose. Airway constriction varied substantially with dose-equivalent stimulation and varied sequentially from trachea (8.8 +/- 2.2% change in airway diam) to fifth-generation bronchus (49.8 +/- 3.0%; P less than 0.001). Length-tension curves were generated for each airway to determine the airway diameter (i.e., resting in situ smooth muscle length) at which maximal constriction was elicited using bolus intravenous injection of 10(-8) mol/kg MCh. A Frank-Starling relationship was obtained for each airway; the transpulmonary pressure at which maximal constriction was elicited increased progressively from 2.50 +/- 1.12 cmH2O for trachea (approximately FRC) to 18.3 +/- 1.05 cmH2O for fifth-generation airways (approximately 50% TLC) (P less than 0.001). A similar relationship was obtained when change in airway diameter was plotted as a function of airway radius. We demonstrate substantial heterogeneity in the lung volumes at which maximal constriction is elicited and in distribution of parasympathomimetic constriction within the first few generations of resistance bronchi. Our data also suggest that lung hyperinflation may lead to augmented airway contractile responses by shifting resting smooth muscle length toward optimum resting smooth muscle length.
Neurohumoral and cardiopulmonary response to sustained submaximal exercise in the dog
Authors: Kirlin P. C. , Kittleson M. D. , Johnson L. E.
Published: December 2017

Neurohumoral, cardiovascular, and respiratory parameters were evaluated during sustained submaximal exercise (3.2 km/h, 15 degrees elevation) in normal adult mongrel dogs. At the level of activity achieved (fivefold elevation of total body O2 consumption and threefold elevation of cardiac output), significant (P less than 0.05) increases in plasma norepinephrine and epinephrine concentration (from 150 +/- 23 to 341 +/- 35 and from 127 +/- 27 to 222 +/- 31 pg/ml, respectively) were present, as well as smaller but significant increases in plasma renin activity and plasma aldosterone concentration (from 2.2 +/- 0.3 to 3.1 +/- 0.6 ng X ml-1 X h-1 and from 98 +/- 8 to 130 +/- 6 pg/ml, respectively). Plasma arginine vasopressin increased variably and insignificantly. The cardiovascular response (heart rate, systemic arterial and pulmonary arterial pressures, left ventricular filling pressure, and calculated total peripheral and pulmonary arteriolar resistance) closely paralleled that of human subjects. Increased hemoglobin concentration was induced by exercise in the dogs. The ventilatory response of the animals was characterized by respiratory alkalosis. These data suggest similarities between canine and human subjects in norepinephrine, plasma renin activity, and plasma aldosterone responses to submaximal exercise. Apparent species differences during submaximal exertion include greater alterations of plasma epinephrine concentration and a respiratory alkalosis in dogs.
Relation between complement activation and susceptibility to decompression sickness
Authors: Ward C. A. , McCullough D. , Fraser W. D.
Published: December 2017

The consequences of complement activation and the symptoms of decompression sickness are similar. Consequently, the relation between the sensitivity of individuals to complement activation by air bubbles and their susceptibility to decompression sickness has been examined. Plasma samples from 34 individuals were incubated with air bubbles, and the concentration of the fluid phase metabolites of complement activation C3a, C4a, and C5a were measured with radioimmunoassays. It was found that both the anaphylatoxins C3a and C5a were produced by the presence of air bubbles but that the anaphylatoxin C4a was not. This finding indicates that air bubbles activate the complement system by the alternate pathway. One group of individuals was found to be particularly sensitive to complement activation by this pathway. They produced 3.3 times more C3a and 5.3 times more C5a in their plasma samples incubated with air bubbles as did the other group. Sixteen individuals were subjected to a series of pressure profiles that were severe enough to produce bubbles in their circulatory system that could be detected by Doppler ultrasonic monitoring. The group of individuals that had been identified as being more sensitive to complement activation by the alternate pathway was also found to be more susceptible to decompression sickness.
Epithelial and endothelial flux after bypass in dogs: effect of positive end-expiratory pressure
Authors: Nolop K. B. , Braude S. , Taylor K. M. , Royston D.
Published: December 2017

Cardiopulmonary bypass (CPB) causes lung injury that occasionally progresses to the adult respiratory distress syndrome (ARDS). We measured the effect of 10 cmH2O of positive end-expiratory pressure (PEEP) on small solute and protein flux in dogs 1 wk before and 2 h after the completion of CPB. As an index of alveolar epithelial permeability, the clearance from lung to blood of inhaled technetium-99m-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA) was measured. To assess microvascular endothelial integrity, the rate of accumulation in the lung interstitium of intravascular 113mIn-transferrin was measured. The clearance half time (t 1/2) for 99mTc-DTPA in the study dogs declined from 18.8 +/- 1.9 min (mean +/- SE) at base line to 9.4 +/- 2.0 min during PEEP (P less than 0.05). Two hours after CPB, the t 1/2 was 8.1 +/- 1.6 min at base line and unchanged during PEEP. The 113mIn-transferrin rate of accumulation was unchanged by PEEP before CPB. After CPB, the index was 3.25 +/- 0.95 slope/min X 10(-3) (P less than 0.05). Of the five dogs with a significant slope, four showed a decrease in microvascular flux during PEEP, although for the group the mean change in slope was not significant (P = 0.10). We conclude that the application of PEEP does not increase 99mTc-DTPA clearance in lungs already injured by CPB, and may actually decrease the apparent microvascular protein flux in some cases.
Attenuation of phrenic motor discharge by phrenic nerve afferents
Authors: Speck D. F. , Revelette W. R.
Published: December 2017

Short latency phrenic motor responses to phrenic nerve stimulation were studied in anesthetized, paralyzed cats. Electrical stimulation (0.2 ms, 0.01–10 mA, 2 Hz) of the right C5 phrenic rootlet during inspiration consistently elicited a transient reduction in the phrenic motor discharge. This attenuation occurred bilaterally with an onset latency of 8–12 ms and a duration of 8–30 ms. Section of the ipsilateral C4-C6 dorsal roots abolished the response to stimulation, thereby confirming the involvement of phrenic nerve afferent activity. Stimulation of the left C5 phrenic rootlet or the right thoracic phrenic nerve usually elicited similar inhibitory responses. The difference in onset latency of responses to cervical vs. thoracic phrenic nerve stimulation indicates activation of group III afferents with a peripheral conduction velocity of approximately 10 m/s. A much shorter latency response (5 ms) was evoked ipsilaterally by thoracic phrenic nerve stimulation. Section of either the C5 or C6 dorsal root altered the ipsilateral response so that it resembled the longer latency contralateral response. The low-stimulus threshold and short latency for the ipsilateral response to thoracic phrenic nerve stimulation suggest that it involves larger diameter fibers. Decerebration, decerebellation, and transection of the dorsal columns at C2 do not abolish the inhibitory phrenic-to-phrenic reflex.
Homeostatic regulation of airway smooth muscle tone by catecholamine secretion in swine
Authors: White S. R. , Sands M. F. , Popovich K. J. , Murphy T. M. , Munoz N. M. , Blake J. , Mack M. , Shioya T. , Leff A. R.
Published: December 2017

We studied the homeostatic secretory response of catecholamine secretion elicited by progressive bronchoconstriction in 18 swine in vivo. The potential reserve of the sympathetic nervous system (SNS) was first assessed by exogenous nicotinic stimulation with 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP). A dose of 250 micrograms/kg iv DMPP caused an increase in plasma norepinephrine (NE) concentration from 207 +/- 86 (basal) to 2,625 +/- 448 pg/ml (P less than 0.02) and in plasma epinephrine (EPI) from 10 +/- 5.0 to 1,410 +/- 432 pg/ml (P less than 0.05) in four swine. In four other swine, bronchoconstriction induced by aerosolized prostaglandin F2 alpha caused approximately a fivefold increase in airway resistance without hemodynamic changes. No increase in plasma EPI was observed. However, plasma NE increased from 330 +/- 131 to 1,540 +/- 182 pg/ml (P less than 0.02). In five swine receiving aerosolized acetylcholine (ACh), similar changes in airways resistance were not associated with significant changes in catecholamine concentration when mean arterial blood pressure (MAP) was unchanged. However, inhalation of sufficient ACh to cause a greater than 10% decrease in MAP caused progressive increase in catecholamine secretion. Plasma EPI increased from 32 +/- 16 (MAP = 124 +/- 7 Torr) to 1,165 +/- 522 pg/ml (MAP = 94 +/- Torr). Hypoxemia that occurred with bronchoconstriction (greater than or equal to 50 Torr) did not cause catecholamine secretion. However, severe hypoxemia (PO2 less than 30 Torr) caused large increases in plasma EPI concentrations from 84 +/- 27 to 1,463 +/- 945 pg/ml (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Opposing effects of anesthetics on pressure tolerance and compression rate effect
Authors: Brauer R. W. , Dutcher J. A.
Published: December 2017

Inert gas narcotics increase intrinsic pressure tolerance (1,000Pc) in CD-1 mice but interfere with development of the protective responses raising seizure thresholds during slower compression (e.g., 60Pc). This secondary narcotic effect can block up to 40% of the total attainable increase in Pc. The narcosis susceptible moiety of this compression rate effect develops early, whereas a narcosis resistant remnant accounts for increase in Pc occurring after 90 min of compression or pressure exposure. Pressure conditioning by multiday pressure exposure entails increases in both 60Pc and 1,000Pc and in virtual annullment of the compression rate effect. The effect can be completely blocked by narcotic gases in the conditioning atmosphere. In addition to blocking part of the compression rate effect the presence of narcotic gases under these conditions can reverse the effects of previously established pressure conditioning. 60Pc regresses much more slowly under these conditions than 1,000Pc. Either reversal rate is much more rapid in air at 1 ATA than at 80 ATA under 0.9 atm N2O. The implications of these data are discussed with regard to evaluation of the hypothesis of antagonism between inert gas narcotics and high pressures and to elaboration of the monoamine hypothesis to account for the modification of the compression rate effect by narcotic gases.
Liquid thickness vs. vertical pressure gradient in a model of the pleural space
Authors: Lai-Fook S. J. , Price D. C. , Staub N. C.
Published: December 2017

In recent studies using relatively noninvasive techniques, the vertical gradient in pleural liquid pressure was 0.2–0.5 cmH2O/cm ht, depending on body position, and pleural liquid pressure closely approximated lung recoil (J. Appl. Physiol. 59: 597–602, 1985). We built a model to discover why the vertical gradient in pleural pressure is less than hydrostatic (1 cmH2O/cm). A long rubber balloon of cylindrical shape was inflated in a plastic cylinder. The “pleural” space between the balloon and cylinder was filled with blue-dyed water. With the cylinder vertical, we measured pleural pressure by a transducer through side taps at 2-cm intervals up the cylinder. The pressure was measured with different amounts of water in the pleural space. With a clear separation between the balloon and the container, the vertical gradient in pleural liquid pressure was hydrostatic. As water was withdrawn from the pleural space, the balloon approached the wall of the container. Over an 8-cm-long midregion of the model where the balloon diameter matched the cylinder diameter, the vertical gradient was not hydrostatic and was virtually absent. In this region, the pleural liquid pressure was uniform and equal to the recoil of the balloon. In this section we could not see any pleural space. By scintillation imaging using 99mTc-diethylenetriamine pentaacetic acid in the water, we estimated the thickness of this flat “costal” pleural space to be approximately 20 microns. Radioactive tracer injected at the top of the pleural space appeared by 24 h at the bottom, which indicated a slow drainage of liquid by gravity.(ABSTRACT TRUNCATED AT 250 WORDS)
Cardiorespiratory changes during HCl infusion unrelated to decreases in circulating blood pH
Authors: Orr J. A. , Shams H. , Fedde M. R. , Scheid P.
Published: December 2017

To test the hypothesis that infusion of HCl changes blood pressure and respiration independent of decreases in circulating blood pH, an extracorporeal arteriovenous shunt (20 ml/min) between the femoral artery and vein was installed in anesthetized cats. Into this loop, acid (0.25 M HCl) and, approximately 10 cm downstream, base (0.25 M NaOH) could be infused simultaneously. Likewise, either acid or base could be infused individually. Right ventricular (Prv) and arterial (Pa) blood pressure, tidal volume (VT), and respiratory frequency (fresp) were recorded as well as blood gases and pH in arterial, right ventricular, and shunt loop blood at the reentrance into the animal. When HCl and NaOH were infused simultaneously and at equimolar rates (0.2 mmol/min for 10 min), there was a large increase in Prv, with little change or decrease in Pa. Respiratory frequency was increased, but total ventilation was not elevated because of a concomitant fall in VT. The rise in Prv and increase in fresp were transient in that they could only be evoked during the first HCl-NaOH infusion in a given animal. Repetitive infusions of HCl-NaOH into the same animal failed to elicit the response. Similar transient acid effects were evoked when HCl was infused without NaOH but not when NaOH was infused without HCl. During the second and third infusion of HCl, ventilatory responses were elicited that were explainable by stimulation of known chemoreceptors. The transient rise in Prv and fresp evoked by acid infusion might be explained by release of an agent from blood elements at the tip of the HCl infusion catheter, which in turn would constrict pulmonary vessels and influence breathing.(ABSTRACT TRUNCATED AT 250 WORDS)
Bacterial pneumonia stimulates macromolecule secretion and ion and water fluxes in sheep trachea
Authors: Phipps R. J. , Torrealba P. J. , Lauredo I. T. , Denas S. M. , Sielczak M. W. , Ahmed A. , Abraham W. M. , Wanner A.
Published: December 2017

In vivo instillation of Pasteurella haemolytica (greater than or equal to 10(7) colony-forming units/kg) into a lobar bronchus of sheep produced bacterial pneumonia by 7 days postinoculation. Infection was verified bacteriologically and histologically. Macromolecule secretion and ion and water fluxes were subsequently measured in tracheal tissues in vitro and were compared with values from sham-infected sheep. Macromolecules were radiolabeled with 35SO4 and [3H]threonine, and we measured the secretion of macromolecule-bound radiolabel onto the mucosa. Unidirectional fluxes of Cl-, Na+, and water were measured with radioactive tracers under open-circuit and short-circuit conditions. Lung infection increased basal secretion of bound 35SO4 (by 189%) and bound [3H]-threonine (by 110%). It significantly increased net Na+ absorption under open- and short-circuit conditions and induced open-circuit net absorption of Cl- and water (16 +/- 29 microliters X cm-2 X h-1). These changes were associated with specific recruitment of neutrophils and elevated levels of arachidonate metabolites (thromboxane B2 and leukotriene B4) in the airways. Thus the bacterial pneumonia-induced changes in tracheal mucus secretion may be the result of airway inflammation.
Maturation of spontaneous fetal diaphragmatic activity and fetal response to hypercapnia and hypoxemia
Authors: Ioffe S. , Jansen A. H. , Chernick V.
Published: December 2017

The electromyogram (EMG) of the diaphragm, lateral rectus, and nuchal and hindlimb muscles were studied during spontaneous activity and during hypercapnia or hypoxemia in eight fetal sheep from 0.5 to 0.8 gestation (73–128 days). At the earliest gestational age, diaphragmatic EMG activity was mainly tonic and associated with tonic activity of somatic muscles. The stimulus for the diaphragmatic activity originated centrally. Brief periods of a rapid-eye-movement (REM) state characterized by phasic lateral rectus and diaphragmatic activity and absence of nuchal activity were recognized. Furthermore, from 0.5 to 0.7 gestation onward, activity of all muscles increased. Thereafter increased specificity of activity in relation to the apparent REM and non-rapid-eye-movement (NREM) state occurred. With maturation, phasic diaphragmatic activity increased at the expense of tonic activity. The most striking effect of maturation on apnea was a greater proportion of apnea lasting greater than 1 min, but the total duration of apnea as a percent of a total recording remained unchanged. The quantitative response to hypercapnia during maturation was independent of the pattern of spontaneous diaphragmatic activity. Hypercapnia at 0.5 gestation changed the pattern of diaphragmatic EMG activity from mainly tonic to phasic. Thus the central chemoreceptors and appropriate neuronal pathways are present and functional as early as 0.5 gestation. Hypercapnia at 0.5 gestation caused a shift in diaphragmatic EMG power to lower frequencies similar to that found during control conditions in the older fetus. This might suggest that during maturation there is increased recruitment of phrenic motoneurons. Hypoxemia abolished tonic somatic activity at 0.5 gestation and decreased phasic diaphragmatic activity at more advanced gestational ages. Therefore the central inhibitory mechanisms of hypoxemia are developed by 0.5 gestation.
Cardiorespiratory responses to chemical activation of right ventricular receptors
Authors: Waldrop T. G. , Mullins D. C.
Published: December 2017

Previous reports have shown that activation of left ventricular receptors with sympathetic afferents elicits increases in respiratory output and arterial pressure. The purpose of the present study was to determine whether similar responses are produced by chemical activation of epicardial receptors in the right ventricle. Receptors were stimulated by applying either capsaicin (10 micrograms) or bradykinin (500 ng) to the epicardial surface of the right ventricle in anesthetized cats. Application of either chemical evoked an increase in respiratory output (phrenic nerve activity), a decrease in heart rate, and a nonsignificant increase in arterial pressure in intact cats. However, capsaicin and bradykinin produced significant increases in arterial pressure, heart rate, and respiratory output after bilateral cervical vagotomy. In contrast, a fall in both heart rate and arterial pressure with only small increases in respiratory output were evoked after bilateral removal of the stellate ganglia in cats with intact vagi. Only small responses to the chemical stimulation of right ventricular receptors persisted after combined vagotomy and stellate ganglionectomy. These findings suggest that 1) activation of epicardial receptors with sympathetic afferents originating in the right ventricle causes an increase in cardiorespiratory function, and 2) activation of right ventricular receptors with vagal afferents produces decreases in heart rate and arterial pressure.
An analysis of decrements in vital capacity as an index of pulmonary oxygen toxicity
Authors: Harabin A. L. , Homer L. D. , Weathersby P. K. , Flynn E. T.
Published: December 2017

Decrements in vital capacity (% delta VC) were proposed by the Pennsylvania group in the early 1970s as an index of O2-induced lung damage. These workers used the combined effects of PO2 and time of exposure to develop recommendations to limit expected % delta VC. Adopting this general approach, we fitted human pulmonary O2 toxicity data to the hyperbolic equation % delta VC = Bs.(PO2 - B1).(time)B3 using a nonlinear least squares analysis. In addition to the data considered in 1970, our analysis included new data available from the literature. The best fit was obtained when 1) an individual slope parameter, Bs, was estimated for each subject instead of an average slope; 2) PO2 asymptote B1 = 0.38 ATA; and 3) exponent B3 = 1.0. Wide individual variation imposed large uncertainty on any % delta VC prediction. A 12-h exposure to a PO2 of 1 ATA would be expected to yield a median VC decrement of 4%. The 80% confidence limits, however, included changes from +1.0 and -12% delta VC. Until an improved index of pulmonary O2 toxicity is developed, a simplified expression % delta VC = -0.011.(PO2 – 0.5).time (PO2 in ATA and time in min) can be used to predict a median response with little loss in predictability. The limitations of changes in VC as an index are discussed.
Adrenal hormones enhance glycogenolysis in nonexercising muscle during exercise
Authors: McDermott J. C. , Elder G. C. , Bonen A.
Published: December 2017

The purpose of this study was to investigate whether epinephrine exerts an effect on glycogen metabolism in nonexercising (Non-Ex) as well as in exercising (Ex) skeletal muscle. Rats ran (15 m/min; 8% grade) on their forelimbs while their hindlimbs (Non-Ex) were suspended above the treadmill. Electromyographic records confirmed the lack of significant contractile activity in muscles during suspension. Plasma epinephrine levels were manipulated in three experimental groups (n = 20 for each group): adrenalectomized (ADX), intact adrenals (IA), and IA + epinephrine injection (+Ep). Another group of rats performed normal exercise on all four limbs (15 m/min; 8% grade). Muscle glycogen levels were measured in selected hindlimb muscles at t = 0 and after 90 min exercise (15 m/min; 8% grade) or suspended rest. In the absence of epinephrine (ADX), no glycogen loss was found (P greater than 0.05) in Non-Ex muscles during the exercise period. In the IA group (epinephrine levels elevated sixfold above basal at t = 90 min), glycogen levels in the nonexercising soleus, plantaris, and red and white gastrocnemius were significantly (P less than 0.05) depleted to 62 +/- 6, 67 +/- 6, 58 +/- 5, and 67 +/- 9% of control values, respectively. Similar decrements occurred in these muscles when exercise was performed on all four limbs (P greater than 0.05). We conclude that glycogenolysis occurs in nonexercising skeletal muscle independent of contractile activity, probably due to the effect of epinephrine. Furthermore, the present data strongly suggest that glycogen depletion patterns in muscles during exercise cannot be used as an index of motor unit recruitment.
Determination of 18O by prompt nuclear reaction analysis: application for measurement of microsamples
Authors: Bradshaw S. D. , Cohen D. , Katsaros A. , Tom J. , Owen F. J.
Published: December 2017

A method is described for the routine determination of 18O concentrations in microsamples of biological fluids. The method utilizes the prompt nuclear reaction 18O(p, alpha o)15N, and 846-keV protons from a 3-MeV Van de Graaff Accelerator are focused on approximately 2,000-A-thick Ta2O5 targets prepared by anodic oxidation from 50-microliter samples of water distilled from blood or other biological fluids. The broad cross section of the resonance peak for this nuclear reaction (47 keV) ensures high yields, especially at small reaction angles, and the high-energy alpha particles produced by the reaction (4 MeV) are readily separated from scattered protons by the use of an aluminized Mylar foil of suitable thickness. Background levels of 18O (0.204 atom%) can be detected with run times of approximately 5–8 min, and the sensitivity of the method is of the order of 0.05 atom %. Experimental error due to sample preparation was found to be 1.7%, and counting errors were close to theoretical limits so that total error was of the order of 2.5%. Duplicate samples were analyzed by use of the 18O(p, alpha o)15N reaction at Lucas Heights, Australia, and the 18O(p,n)18F reaction by the method of Wood et al. (Anal. Chem. 47: 646–650, 1975) at the University of California, Los Angeles, and the agreement was excellent (y = 1.0123x - 0.0123, r = 0.991, P less than 0.001). The theoretical limitations and the general applicability of the method in biological studies designed to estimate the rate of metabolism of free-ranging animals are discussed.
Effect of exercise on insulin binding and glucose transport in adipocytes of normal humans
Authors: Koivisto V. A. , Yki-Jarvinen H.
Published: December 2017

Acute exercise increases insulin binding to its receptors on blood cells. Whether the enhanced insulin binding explains the exercise-induced increase in glucose uptake is unclear, since insulin binding and glucose uptake have not been measured simultaneously in a target tissue of insulin. In this study, we determined insulin binding and the rate of glucose transport in adipocytes obtained by needle biopsy from 10 healthy men before and after 3 h of cycle-ergometric exercise. During the exercise, plasma glucose (P less than 0.01) and insulin (P less than 0.001) fell and serum free fatty acid level rose 4.3-fold (P less than 0.001). 125I-insulin binding to adipocytes remained unchanged during exercise. The rate of basal glucose transport clearance fell from 28.1 +/- 5.7 fl.cell-1.s-1 to 22.9 +/- 5.6 fl.cell-1.s-1 (P less than 0.005), and the insulin-stimulated increase in glucose transport rate rose from 196 +/- 26 to 279 +/- 33% (P less than 0.025) during the exercise. Thus, in the adipocytes during exercise, the basal glucose transport rate and the responsiveness of glucose transport to insulin changed in the absence of alterations in insulin binding. These data indicate that the exercise-induced changes in insulin binding show tissue specificity and do not always parallel alterations in glucose transport.
A technique for recording from intact phrenic nerve afferents
Authors: Revelette W. R. , Frazier D. T.
Published: December 2017

Recent evidence has suggested that phrenic nerve afferents can influence respiratory motor drive. This paper presents a technique whereby the activity of single phrenic nerve afferents can be recorded from uncut dorsal root filaments. Cervical dorsal roots 4, 5, and 6 were exposed by dorsal laminectomy in 10 anesthetized, spontaneously breathing cats. A stimulating electrode was placed on the right whole phrenic nerve low in the neck. The animal was then placed in a spinal suspension frame. Dissection of the dorsal root filaments was performed with probes made of fine tungsten wire. Single filaments were isolated intact from the dorsal root fascicles and placed across a tungsten electrode. Fiber classification was performed by determining conduction velocity. Monopolar recordings were made from a total of 38 fibers. Tonic activity was observed in 21, respiratory-related activity was evident in 15, and two fibers were silent but could be recruited by phrenic nerve stimulation. The conduction velocities ranged from 2.2 to 103 m/s. Approximately one-half of the fibers had conduction velocities of less than 20 m/s. This technique offers a way to record the activity of diaphragm afferents while maintaining the integrity of possible reflex pathways. Application of this method should prove helpful in elucidating the possible role of the various diaphragm afferents in the control of respiratory motor drive.
Effects of intense swimming and tetanic electrical stimulation on skeletal muscle ions and metabolites
Authors: Lindinger M. I. , Heigenhauser G. J. , Spriet L. L.
Published: December 2017

The purpose of this study was to compare changes in ions and metabolites in four different rat hindlimb muscles in response to intense swimming exercise in vivo (263 +/- 33 s) (SWUM), and to 5 min (300 s) of tetanic electrical stimulation of artificially perfused rat hindlimbs (STIM). With both swimming and electrical stimulation, soleus (SOL) contents of creatine phosphate (CP), ATP, and glycogen changed the least, whereas the largest decreases in these metabolites occurred in the white gastrocnemius (WG). Lactate (La-) accumulation and glycogen breakdown were significantly greater in SWUM hindlimb muscles compared with STIM. The high arterial La- concentration [( La-] = 20 meq.l-1) in SWUM may have contributed to elevated muscle [La-], whereas one-pass perfusion kept arterial [La-] below 2 meq.l–1 in STIM. In SWUM, intracellular [Na+] increased significantly in the plantaris (PL), red gastrocnemius (RG), and WG, but not in SOL. [Cl-] increased, and [K+], [Ca2+], and [Mg2+] decreased in all muscles. In STIM, intracellular [K+], [Mg2+], and [Ca2+] decreased significantly, whereas [Na+] and [Cl-] increased in all muscles. Differences in the magnitude of ion and fluid fluxes between groups can be explained by the different methods of hindlimb perfusion. In conclusion, STIM is a useful model of in vivo energy metabolism and permits mechanisms of transsarcolemmal ion movements to be studied.
In vivo estimation of tracheal distensibility and hysteresis in normal adults
Authors: Hoffstein V. , Castile R. G. , O'Donnell C. R. , Glass G. M. , Strieder D. J. , Wohl M. E. , Fredberg J. J.
Published: December 2017

We used the acoustic reflection technique to measure the cross-sectional area of tracheal and bronchial airway segments of eight healthy adults. We measured airway area during a slow continuous expiration from total lung capacity (TLC) to residual volume (RV) and during inspiration back to TLC. Lung volume and esophageal pressure were monitored continuously during this quasi-static, double vital capacity maneuver. We found that 1) the area of tracheal and bronchial segments increases with increasing lung volume and transpulmonary pressure, 2) the trachea and bronchi exhibit a variable degree of hysteresis, which may be greater or less than that of the lung parenchyma, 3) extrathoracic and intrathoracic tracheal segments behaved as if they were subjected to similar transmural pressure and had similar elastic properties, and 4) specific compliance (means +/- SE) for the intrathoracic and bronchial segments, calculated with the assumption that transmural pressure is equal to the transpulmonary pressure, was significantly (P less than 0.05) smaller for the intrathoracic segment than for the bronchial segment: (2.1 +/- 2.0) X 10(-3) cmH2O-–1 vs. (9.1 +/- 2.1) X 10(-3) cmH2O–1. Direct measurements of airway area using acoustic reflections are in good agreement with previous estimates of airway distensibility in vivo, obtained by radiography or endoscopy.
Effects of hyperoxia on vasoconstriction and VA/Q matching in the neonatal lung
Authors: Truog W. E. , Redding G. J. , Standaert T. A.
Published: December 2017

Exposure of adult animals to 48–72 h of 100% O2 breathing is associated with a blunting of hypoxic pulmonary vasoconstriction (HPV) (Newman et al. J. Appl. Physiol. 54: 1379–1386, 1983). It is unknown whether HPV is also diminished in neonates after hyperoxic exposure and if so to what extent such suppression might interfere with pulmonary gas exchange during hypoxic gas breathing. We tested the possibility that hyperoxia would suppress HPV and interfere with ventilation-perfusion (VA/Q) matching and therefore gas exchange in neonatal piglets. Twelve 2- to 4-wk-old piglets were exposed for an average of 68 h to greater than 90% inspired O2. A control group of eight piglets was exposed to room air for a similar period of time. Immediately after exposure the animals were anesthetized and instrumented. Pulmonary hemodynamics and respiratory and inert gas exchange were assessed while the animals inspired an O2 fraction of 1.0, 0.21, and 0.12. After 20 min of hypoxic gas breathing, pulmonary arterial pressure rose to a lesser degree in the hyperoxia (H)-exposed animals than in the control (C) animals (P less than 0.02). The increase in pulmonary vascular resistance was similarly blunted. Venous admixture of the insoluble inert gas, sulfur hexafluoride, an index of extremely low VA/Q areas, was increased during hypoxic gas breathing compared with room air breathing in the H-preexposed animals (P less than 0.02). Standard deviation of pulmonary blood flow was increased (P less than 0.02), indicating an increase in mismatching of VA/Q during hypoxic breathing in the H-preexposed animals compared with the C animals.(ABSTRACT TRUNCATED AT 250 WORDS)