bluuebunny/crossref_metadata_2025 huggingface dataset:
Time of application of negative pressure pulses and upper airway muscle activity
Authors: Woodall D. L. , Hokanson J. A. , Mathew O. P.
Published: December 2017

Effect of upper airway pressure changes on thoracic inspiratory muscles has been shown to depend on the time of application during the breathing cycle. The present study was designed to investigate the importance of the time of application of upper airway negative pressure pulses on upper airway muscles. The upper airway was functionally isolated into a closed system in 24 anesthetized spontaneously breathing rabbits. Negative pressure pulses were applied in early (within the first 200 ms) and late (greater than or equal to 200 ms) inspiration, while electromyograms (EMG) of the diaphragm (Dia), genioglossus (GG), alae nasi (AN), and/or posterior cricoarytenoid (PCA) muscles were simultaneously monitored. When negative pressure pulse was applied in early inspiration, the increase in GG activity was greater [0.49 +/- 0.37 to 4.24 +/- 3.71 arbitrary units (AU)] than when negative pressure was applied in late inspiration (0.44 +/- 0.29 to 2.64 +/- 3.05 AU). Similarly, increased activation of AN (2.63 +/- 1.01 to 4.26 +/- 1.69 AU) and PCA (3.46 +/- 1.16 to 6.18 +/- 2.93 AU) was also observed with early inspiratory application of negative pressure pulses; minimal effects were seen in these muscles with late application. An inhibitory effect on respiratory timing consisting of a prolongation in inspiration (TI) and a decrease in peak Dia EMG/TI was observed as previously reported. These results indicate that the time of application of negative pressure during the breathing cycle is an important variable in determining the magnitude of the response of upper airway muscles.(ABSTRACT TRUNCATED AT 250 WORDS)
A system to reproduce and quantify the biomechanical environment of the cell
Authors: Winston F. K. , Macarak E. J. , Gorfien S. F. , Thibault L. E.
Published: December 2017

An in vitro system that permits application of a uniform biomechanical stimulus to a population of cells with great precision has been developed. The device is designed to subject living cells to reproducible and quantifiable biaxial strains from 0 to 10% at rates from quasi-static to 1 s-1 and frequencies from 0 to 5 Hz. Equations for determining the strain in the substrate upon which the cells are grown, based on easily measured parameters, are derived and validated experimentally. The mechanical properties of the substrate are determined, and it is demonstrated that cells can easily be cultured in the apparatus. By use of the system, cloned bovine pulmonary artery endothelial cell clones are subjected to 5% biaxial strains applied at a peak strain rate of 0.5 s-1 and a frequency of 1 Hz for 7 h with cell viability greater than 84% and cell detachment less than 8%. We demonstrate that cells must be attached to the substrate for them to be stretched and that cell strain and substrate strain are not equal. With the use of fluorescently labeled beads as cell surface markers to measure the actual strain produced in the cells as a result of the deformation of the substrate, cell elongation was found to be approximately 60% of the strain in the substrate. This constant appeared to be affected by both in vitro cell age and morphology.
A PAF antagonist blocks antigen-induced airway hyperresponsiveness and inflammation in sheep
Authors: Soler M. , Sielczak M. W. , Abraham W. M.
Published: December 2017

We studied the effects of WEB-2086, a specific antagonist of platelet-activating factor (PAF), on the development of antigen-induced airway hyperresponsiveness and inflammation in sheep (n = 8). For these studies, airway responsiveness was determined from slopes of carbachol dose-response curves (DRC) performed at base line (prechallenge) and 2 h after Ascaris suum antigen challenges in the following three protocols: 1) antigen challenge alone (control trial), 2) WEB-2086 (1 mg/kg iv) given 30 min before antigen challenge (WEB pretreatment), and 3) WEB-2086 given 2 h after antigen challenge, immediately before the postchallenge DRC (WEB posttreatment). Airway inflammation was assessed by bronchoalveolar lavage (BAL) before antigen challenge and after the postchallenge DRC for each trial. A. suum challenge resulted in acute increases in specific lung resistance that were not different among the three trials. Antigen challenge (control trial) caused a 93% increase (P less than 0.05) in the slope of the carbachol DRC when compared with the prechallenge value. WEB pretreatment (1 mg/kg) reduced (P less than 0.05) this antigen-induced hyperresponsiveness, whereas pretreatment with a 3-mg/kg dose completely prevented it. WEB posttreatment was ineffective in blocking this hyperresponsiveness. BAL neutrophils increased after antigen challenge in the control trial and when WEB-2086 was given after antigen challenge (P less than 0.05). Pretreatment with WEB-2086 (1 or 3 mg/kg) prevented this neutrophilia. This study provides indirect evidence for antigen-induced PAF release in vivo and for a role of endogenous PAF in the modulation of airway responsiveness and airway inflammation after antigen-induced bronchoconstriction in sheep.
Mathematical analysis of running performance and world running records
Authors: Peronnet F. , Thibault G.
Published: December 2017

The objective of this study was to develop an empirical model relating human running performance to some characteristics of metabolic energy-yielding processes using A, the capacity of anaerobic metabolism (J/kg); MAP, the maximal aerobic power (W/kg); and E, the reduction in peak aerobic power with the natural logarithm of race duration T, when T greater than TMAP = 420 s. Accordingly, the model developed describes the average power output PT (W/kg) sustained over any T as PT = [S/T(1 - e-T/k2)] + 1/T integral of T O [BMR + B(1 - e-t/k1)]dt where S = A and B = MAP - BMR (basal metabolic rate) when T less than TMAP; and S = A + [Af ln(T/TMAP)] and B = (MAP - BMR) + [E ln(T/TMAP)] when T greater than TMAP; k1 = 30 s and k2 = 20 s are time constants describing the kinetics of aerobic and anaerobic metabolism, respectively, at the beginning of exercise; f is a constant describing the reduction in the amount of energy provided from anaerobic metabolism with increasing T; and t is the time from the onset of the race. This model accurately estimates actual power outputs sustained over a wide range of events, e.g., average absolute error between actual and estimated T for men's 1987 world records from 60 m to the marathon = 0.73%. In addition, satisfactory estimations of the metabolic characteristics of world-class male runners were made as follows: A = 1,658 J/kg; MAP = 83.5 ml O2.kg-1.min-1; 83.5% MAP sustained over the marathon distance. Application of the model to analysis of the evolution of A, MAP, and E, and of the progression of men's and women's world records over the years, is presented.
CO2 sensitivity changes during the menstrual cycle
Authors: Dutton K. , Blanksby B. A. , Morton A. R.
Published: December 2017

A study of the changes in CO2 sensitivity at rest was undertaken in 20 regularly menstruating females in an attempt to determine the influence of the menstrual cycle on this variable. A biphasic oral temperature graph was used to signify fertility and demarcate three phases of the cycle. A CO2-rebreathing test was conducted 3 times/wk for 6 wk to obtain CO2 sensitivity and CO2 threshold measures. An analysis of variance was used to compare the results collected in each phase of the cycle for each of the variables. A significant increase was found in the sensitivity to CO2 between the follicular and luteal phases, a significant decrease between the luteal and menstrual phases, and no significant difference between the follicular and menstrual phases. The change between follicular and luteal phases was attributed to the effect of progesterone, which is elevated during the luteal phase. No significant change was found in the CO2 threshold level.
Contrasting effects of inflammatory stimuli on neutrophil and monocyte adherence to endothelial cells
Authors: Kamp D. W. , Bauer K. D. , Knap A. , Dunn M. M.
Published: December 2017

Leukocyte adherence to endothelial cells (EC) is an important early event in inflammatory responses, which are often characterized by a predominance of either neutrophils (PMN) or monocytes. However, there is little information concerning the molecular events important in leukocyte adherence to EC. Intracellular activation of protein kinase C and the calcium-second messenger system leads to the stimulation of a number of important functions in PMN and monocytes. We compared the effects of members of these pathways on human PMN and monocyte adherence to cultured bovine aortic EC. We observed that phorbol myristate acetate, phorbol, 12,13-dibutyrate, L-alpha-1-oleoyl-2-acetoyl-sn-3-glycerol, and ionomycin each induced significant dose-dependent increases in PMN adherence to EC monolayers. In contrast, similar concentrations of each of these agents induced significant decreases in EC adherence of monocytes enriched by countercurrent centrifugal elutriation. Separate experiments determined that the differences in PMN and monocyte adherence to EC were not related to differences in oxidant production because 1) phorbol myristate acetate and L-alpha-1-oleoyl-2-acetoyl-sn-3-glycerol caused similar marked increases in both PMN and monocyte superoxide anion and hydrogen peroxide production and 2) ionomycin, which had opposing effects on PMN and monocyte adherence, had no effect on PMN and monocyte superoxide anion or hydrogen peroxide release. We conclude that activators of protein kinase C and the Ca-second messenger pathway have opposite effects on PMN and monocyte adherence to EC and that these effects are mediated by O2 radical-independent mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of hypoxia on thermal polypnea in intact and carotid body-denervated conscious cats
Authors: Bonora M. , Gautier H.
Published: December 2017

The effects of the level of oxygenation on the respiratory response to heat exposure have been studied in conscious cats during normoxia, severe or mild hypocapnic hypoxia [inspired O2 fraction (FIO2) = 0.11 or 0.13], or hyperoxia. Several cats were also studied during severe normocapnic hypoxia. Experiments were repeated while the same animals were chronically carotid body denervated (CBD). The increase in respiratory frequency (f) leading to thermal tachypnea occurred at a lower body temperature (Tb) in severe hypocapnic hypoxia than in ambient air, but this effect was less pronounced when hypocapnia was corrected. No significant changes were observed during mild hypoxia or hyperoxia compared with normoxia in intact animals. After CBD, thermal tachypnea occurred at lower Tb in air than it did with intact animals in three of five cats, and it also occurred at lower Tb in mild hypocapnic hypoxia compared with air. It appears, therefore, that in conscious cats exposed to heat load 1) severe hypoxia enhances thermal tachypnea, 2) this effect persists after CBD, which suggests that it originates from a central action of hypoxia, and 3) the chemoreceptor afferents, to some degree, inhibit the onset of thermal tachypnea, as was previously observed for hypoxic tachypnea, which appears only in CBD cats (J. Appl. Physiol. 49: 769–777, 1980). Therefore, triggering of thermal and hypoxic tachypnea may involve common central mechanisms, probably located in the diencephalic structures under the control of afferents from arterial chemoreceptors.
Surfactant replacement attenuates the increase in alveolar permeability in hyperoxia
Authors: Engstrom P. C. , Holm B. A. , Matalon S.
Published: December 2017

Rabbits exposed to hyperoxia develop surfactant deficiency, abnormal lung mechanics, and increased permeability to solute. We investigated whether replenishment of depleted alveolar surfactant by the intratracheal instillation of calf lung surfactant extract (CLSE) would mitigate the increase in alveolar permeability to solute. Twenty-eight rabbits were exposed to 100% O2 for 72 h and received intratracheal instillations of 125 mg CLSE (approximately 170 mumol dipalmitoyl phosphatidylcholine) at 24 and 48 h. The interlobar and intralobar distribution of CLSE was quantified by adding [14C]dipalmitoyl phosphatidylcholine liposes into the instillate and measuring the levels of activity in lung tissue. CLSE was nonuniformly distributed in the different lung lobes, the right lower lobe receiving more CLSE than the rest. Alveolar epithelial permeability to solute was assessed by instilling 10 ml isotonic saline, which contained a trace amount of [57Co]cyanocobalamin, in the right lower lobe and measuring the disappearance of the tracer from the alveolar saline and its appearance in the arterial blood during a 1-h period. CLSE treatment was associated with significantly increased 72-h survival in hyperoxia compared with saline-treated controls (number of survivors: 16/17 vs. 5/11, P less than 0.01). CLSE treatment significantly reduced the rate constant for the movement of cyanocobalamin out of the alveolar space (24 +/- 5 vs. 42 +/- 6 min-1 x 10(-3), P less than 0.01) and tracer appearance in the blood at the end of the study (7 +/- 1 vs. 34 +/- 13%, P less than 0.01) when compared with values in saline controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Geometry and kinematics of dog ribs
Authors: Margulies S. S. , Rodarte J. R. , Hoffman E. A.
Published: December 2017

Five anesthetized supine beagle dogs were scanned using a fast, multislice computed tomographic X-ray technique to determine the orientation of the ribs at total lung capacity (TLC) and functional residual capacity (FRC). A plane was fit to each rib using a coordinate system in which the z-axis was aligned approximately cephalocaudally and the x-z-plane coincided with the sagittal midplane. The orientation of each plane was described by “pump-handle” and “bucket-handle” angles. The ribs rotated downward and inward during a passive deflation of the lungs from TLC to FRC. Rib displacement was not uniform: bucket-handle motion was predominant in the upper ribs, and pump- and bucket-handle motions were equal in the lower ribs. The change in the pump-handle angles between TLC and FRC was approximately 6 degrees for ribs 3–8, and the change in the bucket-handle angles decreased with rib number from 16 degrees for rib 3 to 6 degrees for rib 8. Rib shape was described by fitting an ellipse to the data for each rib; the ribs became larger and more circular with increasing rib number.
Epithelial modulation of trachealis muscle tension is calcium and temperature dependent
Authors: Lev A. , Christensen G. C. , Ryan J. P. , Wang M. , Kelsen S. G.
Published: December 2017

The tracheobronchial epithelium produces inhibitory substance(s) that alter the tracheal smooth muscle tension. This study examined the effect of changes in extracellular Ca2+ and temperature in vitro on the tension response of rabbit trachealis muscle to mechanical removal of the epithelium. Tension during acetylcholine- and KCl-induced contractions was examined at 0, 0.75, 1.5, 2.5, and 5 mM bath Ca2+ concentrations and at 37, 30, 23, and 41 degrees C bath temperature. At most extracellular Ca2+ concentrations (i.e., 0.75, 1.5, 2.5, and 5 mM), epithelial removal shifted the acetylcholine concentration response approximately one-half log to the left (P less than 0.001 for each condition) but had no effect on the responses to KCl (P = NS). Reductions in bath Ca2+ to 0 mM eliminated the epithelial inhibitory effect on the acetylcholine response. In contrast to the effects of reductions in Ca2+, cooling the airway to 30 and 23 degrees C progressively diminished the magnitude of the epithelial inhibitory effect. Our results indicate that the influence of the tracheal epithelium on tracheal smooth muscle responses to constrictor agonists is substance specific and can be diminished by reductions in tracheal temperature and extracellular Ca2+ concentration.
Alterations in respiratory muscle activation in the ischemic fatigued canine diaphragm
Authors: Supinski G. S. , DiMarco A. F. , Hussein F. , Altose M. D.
Published: December 2017

The purpose of the present study was to examine the respiratory motor response to diaphragm fatigue. Studies were performed using in situ diaphragm muscle strips dissected from the left costal diaphragm in anesthetized dogs. The left inferior phrenic artery was isolated, and diaphragmatic strip fatigue was elicited by occluding this vessel. Strip tension, strip electromyographic activity, parasternal electromyographic activity, and the electromyogram of the right hemidiaphragm were recorded during spontaneous breathing efforts before, during, and after periods of phrenic arterial occlusion. In separate trials, we examined the neuromuscular responses to phrenic arterial occlusion at arterial PCO2 (PaCO2) of 40, 55, and 75 Torr. No fatigue and no alteration in electromyographic activities were observed in trials at PaCO2 of 40 Torr. During trials at PaCO2 of 55 and 75 Torr, however, diaphragm tension fell, the peak height of the diaphragm strip electromyogram decreased, and the peak heights of the parasternal and right hemidiaphragm electromyograms increased. Relief of phrenic arterial occlusion resulted in a return of strip tension and all electromyograms toward base-line values. In additional experiments, the left phrenic nerve was sectioned in the chest after producing fatigue. Phrenic section was followed by an increase in the peak height of the left phrenic neurogram (recorded above the site of section). This latter finding suggests that diaphragm strip motor drive may be reflexly inhibited during the development of fatigue by neural traffic carried along phrenic afferents.
Acute anemia increases lactate production and decreases clearance during exercise
Authors: Gregg S. G. , Mazzeo R. S. , Budinger T. F. , Brooks G. A.
Published: December 2017

We evaluated whether elevated blood lactate concentration during exercise in anemia is the result of elevated production or reduced clearance. Female Sprague-Dawley rats were made acutely anemic by exchange transfusion of plasma for whole blood. Hemoglobin and hematocrit were reduced 33%, to 8.6 +/- 0.4 mg/dl and 26.5 +/- 1.1%, respectively. Blood lactate kinetics were studied by primed continuous infusion of [U-14C]lactate. Blood flow distribution during rest and exercise was determined from injection of 153Gd- and 113Sn-labeled microspheres. Resting blood glucose (5.1 +/- 0.2 mM) and lactate (1.9 +/- 0.02 mM) concentrations were not different in anemic animals. However, during exercise blood glucose was lower in anemic animals (4.0 +/- 0.2 vs. 4.6 +/- 0.1 mM) and lactate was higher (6.1 +/- 0.4 vs. 2.3 +/- 0.5 mM). Blood lactate disposal rates (turnover measured with recyclable tracer, Ri) were not different at rest and averaged 136 +/- 5.8 mumol.kg-1.min-1. Ri was significantly elevated in both control (260.9 +/- 7.1 mumol.kg-1.min-1) and anemic animals (372.6 +/- 8.6) during exercise. Metabolic clearance rate (MCR = Ri/[lactate]) did not differ during rest (151 +/- 8.2 ml.kg-1.min-1); MCR was reduced more by exercise in anemic animals (64.3 +/- 3.8) than in controls (129.2 +/- 4.1). Plasma catecholamine levels were not different in resting rats, with pooled mean values of 0.45 +/- 0.1 and 0.48 +/- 0.1 ng/ml for epinephrine (E) and norepinephrine (NE), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Influence of pregnancy on ventilatory and carotid body neural output responsiveness to hypoxia in cats
Authors: Hannhart B. , Pickett C. K. , Weil J. V. , Moore L. G.
Published: December 2017

Pregnancy increases ventilation and ventilatory sensitivity to hypoxia and hypercapnia. To determine the role of the carotid body in the increased hypoxic ventilatory response, we measured ventilation and carotid body neural output (CBNO) during progressive isocapnic hypoxia in 15 anesthetized near-term pregnant cats and 15 nonpregnant females. The pregnant compared with nonpregnant cats had greater room-air ventilation [1.48 +/- 0.24 vs. 0.45 +/- 0.05 (SE) l/min BTPS, P less than 0.01], O2 consumption (29 +/- 2 vs. 19 +/- 1 ml/min STPD, P less than 0.01), and lower end-tidal PCO2 (30 +/- 1 vs. 35 +/- 1 Torr, P less than 0.01). Lower end-tidal CO2 tensions were also observed in seven awake pregnant compared with seven awake nonpregnant cats (28 +/- 1 vs. 31 +/- 1 Torr, P less than 0.05). The ventilatory response to hypoxia as measured by the shape of parameter A was twofold greater (38 +/- 5 vs. 17 +/- 3, P less than 0.01) in the anesthetized pregnant compared with nonpregnant cats, and the CBNO response to hypoxia was also increased twofold (58 +/- 11 vs. 29 +/- 5, P less than 0.05). The increased CBNO response to hypoxia in the pregnant compared with the nonpregnant cats persisted after cutting the carotid sinus nerve while recording from the distal end, indicating that the increased hypoxic sensitivity was not due to descending central neural influences. We concluded that greater carotid body sensitivity to hypoxia contributed to the increased hypoxic ventilatory responsiveness observed in pregnant cats.
Transverse images of the human thoracic trachea during forced expiration
Authors: Thiriet M. , Maarek J. M. , Chartrand D. A. , Delpuech C. , Davis L. , Hatzfeld C. , Chang H. K.
Published: December 2017

The thoracic trachea and the proximal portion of the major bronchi were imaged in five normal volunteers during a forced expiration maneuver using a cine-computer-tomography system. Sixteen images of two contiguous slices were obtained in less than 1 is while expiratory flow was recorded at the mouth. The area of the thoracic trachea decreased rapidly as flow rate rose to its maximum and the wave of collapse propagated distally. The compressive narrowing of both the pars membranacea and the ventrolateral wall was asymmetric. A contact area appeared between the posterior and the left lateral walls. In one subject the trachea was imaged during the entire maneuver with a lower scan frequency. By 725 ms after the beginning of the forced expiration, the area had first decreased to 15% of its initial value and then reincreased to 46% of its initial value. It stayed constant for the remainder of the maneuver. The measured maximum air velocity was greater than the estimated local wave velocity.
Relationship of venous PO2 to muscle PO2 during hypoxemia
Authors: Gutierrez G. , Lund N. , Acero A. L. , Marini C.
Published: December 2017

Anesthetized mechanically ventilated rabbits were subjected to progressive hypoxemia (n = 7) to determine the relationship of venous PO2 (PvO2) to skeletal muscle PO2 (PtiO2). Measures of arterial PO2 (PaO2), right atrial PO2 [(PvO2)RA], and hindlimb PO2 [(PvO2)limb], were obtained from the carotid artery, right atrium, and inferior vena cava, just above the level of the iliac bifurcation. Biceps femoris muscle PtiO2 was measured with a surface O2 microelectrode having eight measuring points. PaO2 was decreased from 90.3 +/- 5.4 to 26.8 +/- 0.8 Torr in five consecutive steps, followed by reoxygenation to 105.6 +/- 10.5 (SE) Torr. Measurements were obtained after each decrement in PaO2. A total of 128 measures of PtiO2 were obtained per experimental stage. The mean and distribution of the muscle PtiO2 histogram were determined. Measurements were compared with analysis of variance and the Newman-Keuls post hoc method. (PvO2)limb had similar values as the average muscle PtiO2 (PtiO2) for PaO2 values greater than 52.1 +/- 4.3 Torr, where (PvO2)limb became greater than PtiO2 (P less than 0.05). The lowest measures of (PvO2)limb and PtiO2 were 15.9 +/- 0.7 and 4.0 +/- 0.1 Torr, respectively (P less than 0.01). The PtiO2 histograms showed no evidence of increased microvascular heterogeneity with hypoxemia. We conclude that in hypoxemia PvO2 is greater than muscle PtiO2. This difference may be related to the establishment of significant physicochemical O2 gradients from erythrocyte to tissue cell.
Determinants of bone density among athletes engaged in weight-bearing and non-weight-bearing activity
Authors: Block J. E. , Friedlander A. L. , Brooks G. A. , Steiger P. , Stubbs H. A. , Genant H. K.
Published: December 2017

To identify the factors associated with greater bone density among athletic individuals, we recruited three distinct groups of young male subjects. Twenty were nationally ranked water polo players, 19 were engaged in weight-training programs, and 20 subjects comprised a nonexercising comparison group. All participants had measurements of spinal trabecular and integral bone density by quantitative computed tomography as well as a determination of hip bone density by dual photon absorptiometry. A series of potential predictor variables included maximal O2 uptake, back strength, leg strength, total kilocalories expended per day, body mass index, paraspinous muscle cross-sectional area, percent body fat, daily calcium intake, and age. We found no significant differences for any of the bone density measures between the two groups of athletic subjects, whereas bone density was generally significantly lower among the nonexercisers compared with either exercise group. Correlation analysis found only weak and somewhat inconsistent relationships when each of the subgroups was examined separately; however, when all subjects were assessed collectively, many more correlations reached significance. Paraspinous muscular area was found to be most robust in this regard, being significantly correlated with all three bone density measures (r = 0.33–0.55). By using step-wise regression analysis in each subgroup, we observed a consistent significant contribution (R2 = 0.18–0.44) of paraspinous muscle area to the variability in bone density at the spine and the hip. When the data of all three subgroups were pooled, regression analysis reconfirmed the importance of the muscle parameter (R2 = 0.06–0.27) to bone density variation, but more importantly it showed that differentiation based on exercise status was most significant (R2 = 0.18–0.22).
Hypoxic ventilatory response and arterial desaturation during heavy work
Authors: Hopkins S. R. , McKenzie D. C.
Published: December 2017

Arterial desaturation in athletes during intense exercise has been reported by several authors, yet the etiology of this phenomenon remains obscure. Inadequate pulmonary ventilation, due to a blunted respiratory drive, has been implicated as a factor. To investigate the relationship between the ventilatory response to hypoxia, exercise ventilation, and arterial desaturation, 12 healthy male subjects [age, 23.8 +/- 3.6 yr; height, 181.6 +/- 5.6 cm; weight, 73.7 +/- 6.2 kg; and maximal O2 uptake (VO2max), 63.0 +/- 2.2 ml.kg-1 min-1] performed a 5-min treadmill test at 100% of VO2max, during which arterial blood samples and ventilatory data were collected every 15 s. Alveolar PO2 (PAO2) was determined using the ideal gas equation. On a separate occasion the ventilatory response to isocapnic hypoxia was measured. Arterial PO2 decreased by an average of 29 Torr during the test, associated with arterial desaturation [arterial O2 saturation (SaO2) 92.0%]. PAO2 was maintained; however, alveolar-arterial gas pressure difference increased progressively to greater than 40 Torr. Minimal hypocapnia was observed, despite marked metabolic acidosis. There was no significant correlation observed between hypoxic drives and ventilation-to-O2 uptake ratio or SaO2 (r = 0.1 and 0.06, respectively, P = NS). These data support the conclusions that hypoxic drives are not related to maximal exercise ventilation or to the development of arterial desaturation during maximal exercise.
Reassessment of the interruption technique for measuring flow resistance in humans
Authors: Liistro G. , Stanescu D. , Rodenstein D. , Veriter C.
Published: December 2017

We have previously produced evidence that, in patients with obstructive lung disease, compliance of extrathoracic airways is responsible for lack of mouth-to-alveolar pressure equilibration during respiratory efforts against a closed airway. The flow interruption method for measuring respiratory resistance (Rint) is potentially faced with the same problems. We reassessed the merits of the interruption technique by rendering the extrathoracic airways more rigid and by using a rapid shutter. We measured airway resistance (Raw) with whole body plethysmography during panting (at 2 Hz) and Rint during quiet breathing. Rint and Raw were expressed as specific airway (sGaw) and interruptive conductance (sGint), respectively. In nine healthy subjects (cheeks supported), sGint (0.140 +/- 0.050 s-1.cmH2O-1) was lower (P less than 0.02) than sGaw (0.182 +/- 0.043 s-1.cmH2O-1). By contrast, in 12 patients with severe obstructive lung disease (forced expiratory volume in 1 s/vital capacity = 41.0 +/- 19.8%), sGint (0.058 +/- 0.012 s-1.cmH2O-1) was higher (P less than 0.05) than sGaw (0.047 +/- 0.007 s-1.cmH2O-1), when the cheeks were supported. When the mouth floor was also supported, average values of sGaw (0.048 +/- 0.008 s-1.cmH2O-1) and sGint (0.049 +/- 0.014 s-1.cmH2O-1) became similar. In conclusion, we confirm previous findings in healthy subjects of higher values of Rint, with respect to Raw, probably because of differences in glottis opening between quiet breathing and panting. In airflow obstruction, supporting both the cheeks and the mouth floor decreased sGint, which became similar to sGaw.
Effects of clonidine and dihydralazine on atrial natriuretic factor and cGMP in humans
Authors: Wehling M. , Muller T. , Heim J. M. , Lorenz R. , Witzgall H. , Weil J. , Gerzer R.
Published: December 2017

The effects of a 1-wk treatment with clonidine (75 micrograms/day twice a day) and dihydralazine (25 mg/day twice a day) on base-line levels of plasma atrial natriuretic factor (ANF) and plasma and urinary guanosine 3′,5′-cyclic monophosphate (cGMP) and their changes by acute saline infusion (2 liters) in eight normal subjects were evaluated. Basal ANF was decreased to 65% in the clonidine group compared with both the control and dihydralazine groups. Volume loading increased plasma ANF levels by 30–40% of base-line values in the control and the dihydralazine groups and by 15% in the clonidine group. Basal plasma and urinary cGMP levels were raised by 30 and 90% in the dihydralazine group compared with both other groups. Volume loading increased plasma cGMP levels by 40% in the control and clonidine-treated groups and by 25% in the dihydralazine-treated group. It is concluded that ANF may contribute to hemodynamic effects of clonidine but not to those of dihydralazine. Dihydralazine increases plasma and urinary cGMP, supposedly by direct activation of the soluble guanylate cyclase.
Blunted febrile response to intravenous endotoxin in starved rats
Authors: Shido O. , Nagasaka T. , Watanabe T.
Published: December 2017

The effects of fasting on the febrile responses to intravenous injection of bacterial lipopolysaccharide (LPS; endotoxin) of Escherichia coli were investigated in rats. Ad libitum-fed rats (C) produced a biphasic fever with an increase in the temperature difference between brown adipose tissue and colon and shivering activity (SA). Measurement by a direct calorimeter showed no particular changes in heat loss. Rats starved for 4 days (F4) responded to intravenous LPS with a monophasic fever accompanied by an increase in SA only. However the maximal rise in colonic temperature (Tco) did not differ from C rats. Subsequent 2-day fasting reduced SA and the maximal fever height. Endogenous pyrogen (EP) injected intravenously produced a prompt rise in Tco followed by prolonged hyperthermia in C rats. In the F4 rats, there was no such sustained rise in Tco as a result of intravenous EP. The response in Tco to intravenous prostaglandin E2 (PGE2) was the same in fed and starved rats. The administration of LPS, EP, and PGE2 into the lateral ventricle evoked a similar extent of hyperthermia in C and F4 rats. Because the second phase of fever has been shown to occur after pyrogens are translated into a febrile stimulus within the blood-brain barrier, it is assumed that the functional changes of the blood-brain barrier such as in the permeability of pyrogens or in the sensitivity of pyrogen receptors resulted in the absence of the second phase of fever in starved rats.
Lung pressures and gas transport during high-frequency airway and chest wall oscillation
Authors: Khoo M. C. , Ye T. H. , Tran N. H.
Published: December 2017

The major goal of this study was to compare gas exchange, tidal volume (VT), and dynamic lung pressures resulting from high-frequency airway oscillation (HFAO) with the corresponding effects in high-frequency chest wall oscillation (HFCWO). Eight anesthetized paralyzed dogs were maintained eucapnic with HFAO and HFCWO at frequencies ranging from 1 to 16 Hz in the former and 0.5 to 8 Hz in the latter. Tracheal (delta Ptr) and esophageal (delta Pes) pressure swings, VT, and arterial blood gases were measured in addition to respiratory impedance and static pressure-volume curves. Mean positive pressure (25–30 cmH2O) in the chest cuff associated with HFCWO generation decreased lung volume by approximately 200 ml and increased pulmonary impedance significantly. Aside from this decrease in functional residual capacity (FRC), no change in lung volume occurred as a result of dynamic factors during the course of HFCWO application. With HFAO, a small degree of hyperinflation occurred only at 16 Hz. Arterial PO2 decreased by 5 Torr on average during HFCWO. VT decreased with increasing frequency in both cases, but VT during HFCWO was smaller over the range of frequencies compared with HFAO. delta Pes and delta Ptr between 1 and 8 Hz were lower than the corresponding pressure swings obtained with conventional mechanical ventilation (CMV) applied at 0.25 Hz. delta Pes was minimized at 1 Hz during HFCWO; however, delta Ptr decreased continuously with decreasing frequency and, below 2 Hz, became progressively smaller than the corresponding values obtained with HFAO and CMV.
Elastic moduli of lungs during postnatal development in the piglet
Authors: Mansell A. L. , Moalli R. R. , Calista C. L. , Pipkin A. C.
Published: December 2017

Several manifestations of lung disease during infancy suggest that mechanical interdependence can be relatively high in newborn lungs. To test this possibility, we measured elastic moduli and pleural membrane tension in lungs excised from piglets ranging in age from less than 12 h to 85 days. Near maximum inflation, newborn lungs (less than 12 h, n = 6) had no detectable pleural membrane tension, although 3- to 5-day-old lungs (n = 6) had tension greater than 5,000 dyn/cm. In contrast, parenchymal recoil was greater in the newborn lungs [19.3 +/- 3.0 (SD) vs. 14.3 +/- 2.4 cmH2O at 90% of maximum inflation volume, P less than 0.01]. Shear moduli were higher (13.5 +/- 4.6 vs. 9.2 +/- 1.5 cmH2O at 15 cmH2O transpulmonary pressure, P less than 0.05) and Poisson ratios were lower in the newborn lungs as compared with the 3- to 5-day-old lungs. Postnatal lung growth between 3 and 85 days was characterized by 1) a constant shear modulus (0.6 times transpulmonary pressure); 2) decrease in the bulk modulus (from 6.8 to 5.1 times transpulmonary pressure, P less than 0.005); and 3) evidence of gas trapping at progressively higher transpulmonary pressures. Therefore, growth of parenchyma in the piglet lung is associated with reduced stiffness to volume change but with no effect on overall stiffness to shape change. Nevertheless, a relatively great stiffness to shape change occurs transiently in newborn piglet lungs.
Reflex responses to capsaicin: intravenous, aerosol, and intratracheal administration
Authors: Palecek F. , Sant'Ambrogio G. , Sant'Ambrogio F. B. , Mathew O. P.
Published: December 2017

Intravenous capsaicin elicits the "pulmonary chemoreflex" (apnea, bradycardia, and hypotension) presumably through the stimulation of "pulmonary C-fibers." The present study was designed to ascertain whether tracheobronchial C-fibers play a role in the above reflex response. We compared the effects of capsaicin injected intravenously, administered as an aerosol, and administered topically into the intrathoracic trachea in anesthetized dogs (n = 17) and rats (n = 17). We measured esophageal, subglottic, and arterial pressures together with abdominal muscle electromyogram. Changes in expiratory duration [(TE), measured as the ratio TEtest to TEcontrol, mean +/- SD] due to capsaicin were similar with all three routes of administration in both dogs (intravenous, 7.9 +/- 4.6; aerosol, 5.5 +/- 3.1; topically into intrathoracic trachea, 7.1 +/- 4.8) and rats (intravenous, 22.6 +/- 10.3; aerosol, 11.1 +/- 8.2; topically into intrathoracic trachea, 21.6 +/- 4.6). An increase in laryngeal resistance was a constant finding in the rat, but it was less frequent in the dog. Cardiovascular responses consisting of bradycardia and hypotension occurred with all three routes of administration but had longer delays than the respiratory responses. Capsaicin instillation into the extrathoracic trachea in dogs (n = 7) also induced qualitatively similar cardiorespiratory responses. We conclude that 1) capsaicin-sensitive receptors are accessible from both the pulmonary circulation and the airway lumen and 2) afferents, even in the extrapulmonary portion of the tracheobronchial tree, can play a role in the reflex responses to intraluminal capsaicin.
Rib cage vs. abdominal displacement in dogs during forced oscillation to 32 Hz
Authors: Boynton B. R. , Glass G. , Frantz I. D. , Fredberg J. J.
Published: December 2017

Allen et al. (J. Clin. Invest. 76: 620–629, 1985) reported that during oscillatory forcing the base of isolated canine lungs distends preferentially relative to the apex as frequency and tidal volume increase. The tendency toward such nonuniform phasic lung distension might influence phasic displacement of the rib cage (RC) relative to the abdomen (ABD). To test this hypothesis we measured RC and ABD displacement in four anesthetized dogs during forced oscillation. Sinusoidal volume changes were delivered through a tracheostomy at 1–32 Hz and measured by body plethysmography. RC and ABD displacements were measured by inductive plethysmography. During oscillation with air at fixed tidal volumes (10–80 ml) RC, normalized to unity at 1 Hz, increased to 2.06–2.22 at 8 Hz (P less than 0.001) and then decreased to 1.06–1.35 (P less than 0.0025) at 32 Hz. ABD, normalized to unity at 1 Hz, was 1.12–1.16 at 4 Hz (P less than 0.001) and decreased to 0.12–0.14 at 32 Hz (P less than 0.001). Displacement of ABD relative to RC did not increase systematically with increasing tidal volume during sinusoidal forcing at any frequency. Thus we found no discernible influence of nonuniform phasic lung distension on chest wall behavior. We infer that in the dog the nonuniform mechanical behavior of the chest wall dominates the nonuniform (but opposing) mechanical tendency of the lung.
Acetylcholine's effect on vascular resistance and compliance in the pulmonary circulation
Authors: Barman S. A. , Senteno E. , Smith S. , Taylor A. E.
Published: December 2017

Acetylcholine's effect on the distribution of vascular resistance and compliance in the canine pulmonary circulation was determined under control and elevated vascular tone by the arterial, venous, and double occlusion techniques in isolated blood-perfused dog lungs at both constant flow and constant pressure. Large and small blood vessel resistances and compliances were studied in lungs given concentrations of acetylcholine ranging from 2.0 ng/ml to 200 micrograms/ml. The results of this study indicate that acetylcholine dilates large arteries at low concentrations (less than or equal to 20 ng/ml) and constricts small and large veins at concentrations of at least 2 micrograms/ml. Characterization of acetylcholine's effects at constant pulmonary blood flow indicates that 1) large artery vasodilation may be endothelial-derived relaxing factor-mediated because the dilation is blocked with methylene blue; 2) a vasodilator of the arachidonic acid cascade (blocked by ibuprofen), probably prostacyclin, lessens acetylcholine's pressor effects; 3) when vascular tone was increased, acetylcholine's hemodynamic effects were attenuated; and 4) acetylcholine decreased middle compartment and large vessle compliance under control but not elevated vascular tone. Under constant pressure at control vascular tone acetylcholine increases resistance in all segments except the large artery, and at elevated vascular tone the pressor effects were enhanced, and large artery resistance was increased.
Lung volumes, chest wall configuration, and pattern of breathing in microgravity
Authors: Paiva M. , Estenne M. , Engel L. A.
Published: December 2017

We studied the changes in functional residual capacity (FRC), thoracoabdominal volume (Vw), and chest wall configuration in five normal subjects seated in an aircraft flying parabolic trajectories resulting in 20-s periods of microgravity. We measured vital capacity (VC), inspiratory capacity, and tidal volume by integrating airflow at the mouth and changes in rib cage and abdominal volume (delta Vrc and delta Vab, respectively, where delta Vrc + delta Vab = delta Vw) using induction plethysmography. During microgravity (0 Gz) FRC decreased by 413 +/- 70 (SE) ml and VC by 0.37 liter. The decrease in Vw did not differ from that in FRC and was entirely the result of reduction of Vab, the Vrc showing no significant change. During tidal breathing the abdominal contribution (delta Vab/delta Vw) increased from 0.39 +/- 0.08 at 1 Gz to 0.57 +/- 0.08 at 0 Gz. During brief periods of hypergravity (approximately 1.8 Gz) all changes were opposite in sign and relatively smaller. Limited data during "roller coaster" flight patterns suggested that, in contrast to configurational changes, the temporal pattern of breathing was uninfluenced by changes in Gz. We conclude that at the onset of weightlessness there are substantial changes in lung volume and thoracoabdominal configuration. Abdominal contribution to tidal excursions increases but the temporal pattern of breathing is unchanged.
Surfactant secretion and clearance in the newborn
Authors: Stevens P. A. , Wright J. R. , Clements J. A.
Published: December 2017

Pregnant rabbits (30 days) were injected intravenously with [3H]choline 8 h before delivery. The fetuses were delivered, and lung lavage and lamellar body phospholipids (PL) were analyzed. Some newborns also received radioactively labeled surfactant intratracheally on delivery and were permitted to breathe. With time, intratracheal label decreased in lavage and appeared in the lamellar body fraction, and intravenous label accumulated in both pools. Using a tracer analysis for non-steady state, we calculated surfactant secretion and clearance rates for the newborn period. Before birth, both rates rose slightly from 1.8 micrograms PL.g body wt-1.h-1 at 6 h before birth to 7.3 at birth. Immediately after birth, secretion rate rose to 37.7 micrograms PL.g body wt-1.h-1. Between 1.5 and 2 h after birth it fell to a minimum of 1.8 micrograms PL.g body wt-1.h-1 and then rose slowly to 6.0 at 12 h. After birth, clearance rate increased less than secretion rate (maximum 24.7 micrograms PL.g body wt-1.h-1 shortly after birth) then followed the same pattern but did not balance secretion rate in the 1st day.
Does atrial natriuretic factor protect against right ventricular overload? I. Hemodynamic study
Authors: Ou L. C. , Sardella G. L. , Hill N. S. , Thron C. D.
Published: December 2017

We studied the effects of synthetic atrial natriuretic factor (ANF, 28-amino acid peptide) on base-line perfusion pressures and pressor responses to hypoxia and angiotensin II (ANG II) in isolated rat lungs and on the following hemodynamic and renal parameters in awake, chronically instrumented rats: cardiac output (CO), systemic (Rsa) and pulmonary (Rpa) vascular resistances, ANG II- and hypoxia (10.5% O2)-induced changes in Rsa and Rpa, and urine output. Intra-arterial ANF injections lowered base-line perfusion pressures and blunted hypoxia- and ANG II-induced pressor responses in the isolated lungs. Bolus intravenous injection of ANF (10 micrograms/kg) into intact rats decreased CO and arterial blood pressures of both systemic and pulmonary circulations and increased Rsa. ANG II (0.4 micrograms/kg) increased both Rsa and Rpa, and hypoxia increased Rpa alone in the intact rats. ANF (10 micrograms/kg) inhibited both ANG II- and hypoxia-induced increases in Rpa but did not significantly affect the ANG II-induced increase in Rsa. The antagonistic effect of ANF on pulmonary vasoconstriction was reversible and dose-dependent. The threshold doses of ANF required to inhibit pulmonary vasoconstriction were in the same range as those required to elicit diuresis and natriuresis. The data demonstrate that ANF has a preferential relaxant effect on pulmonary vessels constricted by hypoxia or ANG II. Both the renal and the pulmonary vascular effects of ANF may represent fundamental physiological actions of ANF. These actions may serve as a negative feedback control system that protects the right ventricle from excessive mechanical loads.
Lung impedance in healthy humans measured by forced oscillations from 0.01 to 0.1 Hz
Authors: Suki B. , Peslin R. , Duvivier C. , Farre R.
Published: December 2017

Lung impedance was measured from 0.01 to 0.1 Hz in six healthy adults by superimposing small-amplitude forced oscillations on spontaneous breathing. Measurements were made with an almost constant-volume input (160–180 ml) or with an almost constant-flow input (20–30 ml.s-1). No significant difference was found between the two conditions. Lung resistance (RL) sharply decreased from 0.97 kPa.l-1.s at 0.01 Hz to 0.27 kPa.l-1.s at 0.03 Hz and then mildly to 0.23 kPa.l-1.s at 0.1 Hz. Lung effective compliance (CL) decreased slightly and regularly from 0.01 Hz (2.38 l.kPa-1) to 0.1 Hz (1.93 l.kPa-1). The data were analyzed using a linear viscoelastic model adapted from Hildebrandt (J. Appl. Physiol. 28:365–372, 1970) and complemented by a Newtonian resistance (R): RL = R + B/(9.2f); CL = 1/(A + 0.25B + B.log2 pi f), where f is the frequency and B/A is an index of lung tissue viscoelasticity. A good fit was generally obtained, with an average difference of 10% between the observed and predicted values. The ratio B/A was not affected by the breathing and was 10.6 and 13.6% in the constant-volume and constant-flow conditions, respectively, which agrees with Hildebrandt's observations in isolated cat lungs. R was systematically larger than the plethysmographic airway resistance, suggesting that lung tissue resistance might also include a Newtonian component.
Theophylline does not increase maximal tetanic force or diaphragm endurance in vitro
Authors: Reid M. B. , Miller M. J.
Published: December 2017

These experiments tested the capacity of theophylline to improve diaphragm strength (maximal force development) and endurance (maintenance of force output during repeated contractions). Rodent diaphragm strips were mounted at optimal length in oxygenated Krebs-Ringer solution (37 degrees C, pH 7.37). Direct stimuli used supramaximal current density, 0.2-ms pulses, and 250-ms tetanic trains. Theophylline (500 mg/ml) increased force development at low stimulation frequencies but did not increase maximal force [25.7 +/- 0.5 for theophylline vs. 26.0 +/- 0.4 (SE) N/cm2 for control (n = 34)]. During repeated submaximal (25–36 Hz) tetanic contractions, theophylline did not affect endurance. During repeated maximal (160 Hz) tetanic contractions theophylline reduced endurance, accelerating the fall of developed force. Theophylline also inhibited recovery of force after endurance trials ended. We conclude that theophylline does not increase maximal tetanic force and can reduce diaphragm endurance in vitro.