bluuebunny/crossref_metadata_2025 huggingface dataset:
Ventilatory responses to inspiratory threshold loading in humans
Authors: Yanos J. , Banner A. , Stanko R. , Gentry S. , Greenawalt K.
Published: December 2017

Normal alveolar ventilation tends to be maintained during external mechanical loading. The precise manner by which this occurs is unclear but may involve intrinsic mechanisms related to the muscular pump, neural influences, and chemoreceptor control. Recent observations suggest that submaximal threshold loads may result in hyperventilation. In this study we explicitly examined the respiratory effects of sustained threshold loading in normal subjects. We found that sustained threshold loading resulted in hyperventilation associated with high P100's (mouth pressure 100 ms after the start of an occluded breath) and increased tidal volumes but with little effect on duty cycle or respiratory rate. In addition, this increased respiratory motor output was sustained for 30-60 s after the load was removed. At very high threshold loads, hyperventilation failed to occur, despite increased P100's. We conclude that threshold loading results in increased respiratory motor output and hyperventilation, a response that is different from that observed with either resistive or elastic loads, and that the failure to hyperventilate at the higher loads may be the result of mechanical limitation.
Breathing and lung mechanics in hamsters: effect of pentobarbital anesthesia
Authors: Skornik W. A. , Brain J. D.
Published: December 2017

An adaptation of the method reported by Skornik, Heimann, and Jaeger (Toxicol. Appl. Pharmacol. 59: 314-323, 1981) was used to evaluate pulmonary mechanics in intact awake hamsters. Lung volume changes were measured with a pressure plethysmograph, and pleural pressure was estimated by the use of a saline-filled esophageal catheter. We report data for normal awake hamsters studied at 18, 20, 22, 32, and 98 wk of age. Age-related differences were observed in tidal volume, dynamic compliance, and pulmonary resistance. To determine to what extent pulmonary mechanics are changed by anesthesia, hamsters were measured during spontaneous breathing while awake and while anesthetized. We found that anesthesia had a marked effect on the breathing pattern of normal hamsters. Twenty-five minutes after injection of pentobarbital sodium (70 mg/kg ip), tidal volume, dynamic compliance, pulmonary resistance, breathing frequency, and minute ventilation were 66, 40, 375, 60, and 41% of the corresponding awake values. Anesthesia always provoked a significant and dose-related decrease in tidal volume and an increase in respiratory period, together resulting in a profound decrease in minute ventilation. These significant differences from the awake values call into question the value of measurements in anesthetized animals. The methods described here yield reasonable and repeatable measurements and, because no anesthesia or surgery is required, they can be used in longitudinal studies when repeated measurements in the same animal over long periods of time can help define pathological changes or the effectiveness of various interventions.
Ventilatory control during exercise in calves with artificial hearts
Authors: Huszczuk A. , Whipp B. J. , Adams T. D. , Fisher A. G. , Crapo R. O. , Elliott C. G. , Wasserman K. , Olsen D. B.
Published: December 2017

To determine the role of cardiac reflexes in mediating exercise hyperpnea, we investigated ventilatory responses to treadmill exercise in seven calves with artificial hearts and seven controls. In both groups, the ventilatory responses were adequate for the metabolic demands of the exercise; this resulted in regulation of arterial PCO2 and pH despite the absence of cardiac output increase in the implanted group. In this group, there was a small but significant reduction of arterial PO2 by 4 +/- 3 Torr and a rise of blood lactate by 1.1 +/- 1 mmol/l. When cardiac output was experimentally increased in the implanted calves to a level commensurate with that spontaneously occurring in the control calves, ventilation was not affected. However, experimental reductions of cardiac output led to an immediate augmentation of exercise hyperpnea by 4.56 +/- 4.3 l/min and a further significant lactate increase of 1.2 +/- 1.22 mmol/l that was associated with a significant decrease in the exercise O2 consumption (0.32 +/- 0.13 l/min). These observations indicate that neither cardiac nor hemodynamic effects of increased cardiac output constitute an obligatory cause of exercise hyperpnea in the calf.
Changes in lung liquid dynamics induced by prolonged fetal hypoxemia
Authors: Hooper S. B. , Harding R.
Published: December 2017

Our aim was to determine the effect of prolonged fetal hypoxemia, induced by reduced maternal uterine blood flow (RUBF), on fetal lung liquid secretion, flow, and volume. In chronically catheterized fetal sheep, lung liquid volume (VL) and the secretion rate of lung liquid (Vs) were measured before and after a 24-h period of either RUBF or normoxemia. Tracheal fluid flow and the incidence of fetal breathing movements (FBM) were measured before, during, and after the 24-h period. In normoxic control fetuses Vs was not significantly altered. After 24 h of RUBF, Vs was significantly (P less than 0.005) reduced compared with pre-RUBF values. During 24 h of RUBF the incidence of FBM declined initially but returned to control values after 12-16 h. In seven of eight fetuses, over the 12- to 24-h period of RUBF, large amounts of liquid (22.7-62.6 ml) were drawn into the lungs during FBM, resulting in a net movement of amniotic fluid into the lungs. During the 18- to 24-h period of RUBF, changes in the incidence of FBM were found to be significantly and positively correlated (r = 0.86, P less than 0.005) with the changes in VL that occurred over the 24-h period. Thus, prolonged RUBF can result in the inhalation of large volumes of amniotic fluid by the fetus, which could be a cause of in utero meconium aspiration.
Age-dependent effects of chronic hypoxia on renin-angiotensin and urinary excretions
Authors: Jain S. , Wilke W. L. , Tucker A.
Published: December 2017

The mechanisms regulating water, electrolyte, and blood volume homeostasis continue to mature in early postnatal life, and this maturation may be altered by perturbations of volume or cardiovascular status. To evaluate the long-term effects of chronic hypoxia on water balance, urinary electrolyte excretion, heart weights, systemic arterial pressure, and components of the renin-angiotensin system, male Sprague-Dawley rats were exposed to periods of simulated altitude of 10,000 ft up to 90 days of age beginning at 2 or 30 days of age. Altitude exposure of both neonatal and adult rats was associated with increases in urine output and water intake after 30 days of exposure, and right ventricular (RV) hypertrophy at all ages was examined. However, the percent increase in urine output, water intake, and RV hypertrophy was numerically greater in neonates. Neonates also had increases in urinary sodium and potassium excretion after 30 days of exposure. Plasma renin activity and serum angiotensin-converting enzyme (ACE) activity were not affected, but plasma renin substrate was reduced in both neonatal and adult altitude-exposed rats. Lung ACE activity was also decreased in altitude-exposed neonates. These data indicate that the degree and, in some cases, the nature of these homeostatic responses varies with age during long-term hypoxia.
Effect of raised alveolar pressure on leukocyte retention in the human lung
Authors: Markos J. , Hooper R. O. , Kavanagh-Gray D. , Wiggs B. R. , Hogg J. C.
Published: December 2017

To determine whether an increase in alveolar pressure delays the passage of leukocytes (WBCs) through the lung by compressing the lung capillaries, we measured the concentration of WBC across the lung in response to a forced expiratory maneuver. In 20 human subjects, blood was sampled from catheters placed in the pulmonary artery (PA) and left ventricle (LV) before, during, and after a forced expiratory maneuver held for greater than or equal to 20 s against an occluded airway. Pressures were recorded at the mouth and from both catheters. A significant fall in LV WBC (P less than 0.01) but not in PA WBC occurred during or immediately after the maneuver in 18 subjects, with a mean maximum decrease of 26 +/- 12% (SD) from base line (range 9-46%). Between 1 and 3 min after the maneuver, there was an increase in LV and PA WBC (P less than 0.01) above base line. The neutrophil and lymphocyte counts showed similar changes, but erythrocyte and platelet counts remained unchanged. The degree of fall in LV WBC correlated closely (r = 0.68, P less than 0.01) with the changes from lung zone 3 to zone 2 and 1 conditions, as determined from the pressure changes. We conclude that WBCs are retained in the lung during a forced expiratory maneuver because of alveolar capillary compression.
Isomyosin distributions in rodent muscles: effects of altered thyroid state
Authors: Fitzsimons D. P. , Herrick R. E. , Baldwin K. M.
Published: December 2017

In this study we examined the effects of 6-8 wk of thyroid hormone manipulation on striated muscle isomyosin expression in adult female rats. Animals were randomly assigned to one of three groups: 1) euthyroid controls, 2) thyroid deficient (propylthiouracil treated), and 3) hyperthyroid (triiodothyronine treated). Thyroid deficiency resulted in a marked increase in the low-adenosinetriphosphatase V3 isoform by 20- and 49-fold in the left and right ventricle, respectively. Conversely, hyperthyroidism induced a modest (3-11%) but significant increase in the high-adenosinetriphosphatase V1 isoform in both ventricles. The thyroid-deficient rats exhibited significant increases in slow myosin in both soleus (8%) and red gastrocnemius (24%), with concomitant reductions in intermediate myosin in both muscles. Interestingly, while the slow-myosin isoform was decreased in both the soleus (-19%) and the red gastrocnemius (-43%) of the hyperthyroid group, the intermediate-myosin isoform was affected differentially in the two muscles, with a fivefold increase in the former vs. a 16% decrease in the latter. Furthermore, hyperthyroidism increased the fast myosins in the red gastrocnemius while exerting no effect on the same isoforms in the white gastrocnemius. Collectively these data suggest both different specificity and sensitivity among the myosin genes of different striated muscle types in response to thyroid hormone.
Impaired muscle glycogen resynthesis after eccentric exercise
Authors: Costill D. L. , Pascoe D. D. , Fink W. J. , Robergs R. A. , Barr S. I. , Pearson D.
Published: December 2017

Eight men performed 10 sets of 10 eccentric contractions of the knee extensor muscles with one leg [eccentrically exercised leg (EL)]. The weight used for this exercise was 120% of the maximal extension strength. After 30 min of rest the subjects performed two-legged cycling [concentrically exercised leg (CL)] at 74% of maximal O2 uptake for 1 h. In the 3 days after this exercise four subjects consumed diets containing 4.25 g CHO/kg body wt, and the remainder were fed 8.5 g CHO/kg. All subjects experienced severe muscle soreness and edema in the quadriceps muscles of the eccentrically exercised leg. Mean (+/- SE) resting serum creatine kinase increased from a preexercise level of 57 +/- 3 to 6,988 +/- 1,913 U/l on the 3rd day of recovery. The glycogen content (mmol/kg dry wt) in the vastus lateralis of CL muscles averaged 90, 395, and 592 mmol/kg dry wt at 0, 24, and 72 h of recovery. The EL muscle, on the other hand, averaged 168, 329, and 435 mmol/kg dry wt at these same intervals. Subjects receiving 8.5 g CHO/kg stored significantly more glycogen than those who were fed 4.3 g CHO/kg. In both groups, however, significantly less glycogen was stored in the EL than in the CL.
Effects of expiratory resistive loading on the sensation of dyspnea
Authors: Chonan T. , Altose M. D. , Cherniack N. S.
Published: December 2017

To determine whether an increase in expiratory motor output accentuates the sensation of dyspnea (difficulty in breathing), the following experiments were undertaken. Ten normal subjects, in a series of 2-min trials, breathed freely (level I) or maintained a target tidal volume equal to (level II) or twice the control (level III) at a breathing frequency of 15/min (similar to the control frequency) with an inspiratory load, an expiratory load, and without loads under hyperoxic normocapnia. In tests at levels II and III, end-expiratory lung volume was maintained at functional residual capacity. A linear resistance of 25 cmH2O.1(-1).s was used for both inspiratory and expiratory loading; peak mouth pressure (Pm) was measured, and the intensity of dyspnea (psi) was assessed with a visual analog scale. The sensation of dyspnea increased significantly with the magnitude of expiratory Pm during expiratory loading (level II: Pm = 9.4 +/- 1.5 (SE) cmH2O, psi = 1.26 +/- 0.35; level III: Pm = 20.3 +/- 2.8 cmH2O, psi = 2.22 +/- 0.48) and with inspiratory Pm during inspiratory loading (level II: Pm = 9.7 +/- 1.2 cmH2O, psi = 1.35 +/- 0.38; level III: Pm = 23.9 +/- 3.0 cmH2O, psi = 2.69 +/- 0.60). However, at each level of breathing, neither the intensity of dyspnea nor the magnitude of peak Pm during loading was different between inspiratory and expiratory loading. The augmentation of dyspnea during expiratory loading was not explained simply by increases in inspiratory activity. The results indicate that heightened expiratory as well as inspiratory motor output causes comparable increases in the sensation of difficulty in breathing.
Reflex control of the circulation during exercise: chemoreflexes and mechanoreflexes
Authors: Rowell L. B. , O'Leary D. S.
Published: December 2017

The overall scheme for control is as follows: central command sets basic patterns of cardiovascular effector activity, which is modulated via muscle chemo- and mechanoreflexes and arterial mechanoreflexes (baroreflexes) as appropriate error signals develop. A key question is whether the primary error corrected is a mismatch between blood flow and metabolism (a flow error that accumulates muscle metabolites that activate group III and IV chemosensitive muscle afferents) or a mismatch between cardiac output (CO) and vascular conductance [a blood pressure (BP) error] that activates the arterial baroreflex and raises BP. Reduction in muscle blood flow to a threshold for the muscle chemoreflex raises muscle metabolite concentration and reflexly raises BP by activating chemosensitive muscle afferents. In isometric exercise, sympathetic nervous activity (SNA) is increased mainly by muscle chemoreflex whereas central command raises heart rate (HR) and CO by vagal withdrawal. Cardiovascular control changes for dynamic exercise with large muscles. At exercise onset, central command increases HR by vagal withdrawal and "resets" the baroreflex to a higher BP. As long as vagal withdrawal can raise HR and CO rapidly so that BP rises quickly to its higher operating point, there is no mismatch between CO and vascular conductance (no BP error) and SNA does not increase. Increased SNA occurs at whatever HR (depending on species) exceeds the range of vagal withdrawal; the additional sympathetically mediated rise in CO needed to raise BP to its new operating point is slower and leads to a BP error. Sympathetic vasoconstriction is needed to complete the rise in BP. The baroreflex is essential for BP elevation at onset of exercise and for BP stabilization during mild exercise (subthreshold for chemoreflex), and it can oppose or magnify the chemoreflex when it is activated at higher work rates. Ultimately, when vascular conductance exceeds cardiac pumping capacity in the most severe exercise both chemoreflex and baroreflex must maintain BP by vasoconstricting active muscle.
Catecholamines, circulation, and the kidney during water immersion in humans
Authors: Norsk P. , Bonde-Petersen F. , Christensen N. J.
Published: December 2017

Because results in literature are discrepant with regard to the effects of water immersion (WI) on the release of norepinephrine (NE) in humans, the following study was performed. Simultaneous measurements of plasma NE, central cardiovascular variables, and renal sodium excretion were conducted in eight normal male subjects on 2 study days; 6 h of thermoneutral (35.0 degrees C) WI to the neck were preceded and followed by 1 h in the seated posture outside the water and 8 h of a seated control period. During the control period, the subjects wore a water-perfused garment (water temperature 34.6 degrees C) to obtain the same skin temperature as during WI. The subjects were fluid restricted overnight and kept in this condition throughout the study. Compared with the prestudy, post-study, and control periods, plasma NE decreased significantly by 61% during WI. Simultaneously, central venous pressure, cardiac output, stroke volume, systolic arterial pressure, and arterial pulse pressure increased, whereas heart rate decreased. Renal sodium excretion and urine flow rate increased. In conclusion, the release of NE is suppressed in humans during immersion. This decrease probably reflects a decrease in sympathetic nervous activity initiated by stimulation of low- and high-pressure baroreceptors. It is possible that the decrease in NE acts as one of several mechanisms of the natriuresis and diuresis of immersion in humans.
Reactive absorption of nitrogen dioxide by pulmonary epithelial lining fluid
Authors: Postlethwait E. M. , Langford S. D. , Bidani A.
Published: December 2017

In a previous study (J. Appl. Physiol. 68: 594-603, 1990) in isolated rat lungs, we suggested that the rate of pulmonary air space absorption of inhaled NO2 is limited, in part, by chemical reaction(s) rather than by physical solubility. Because the initial site of primary absorption interactions involves the epithelial lining fluid (ELF), we investigated whether ELF-NO2 interactions could account for pulmonary NO2 reactive absorption. Rat ELF, obtained by bronchoalveolar lavage (BAL), was compared with a model chemical system (reduced glutathione, GSH). In vitro exposures (NO2-air) used constant gas flow and planar gas-liquid interfaces. 1) Solvent pH notably altered NO2 uptake by GSH but to a lesser extent by BAL. 2) Uptake displayed [GSH]-dependent saturation. [ELF] in BAL was augmented by sequential lavage (lavagate reuse) of multiple lungs. Uptake was proportional to [ELF] but did not saturate under these exposure conditions. 3) The uptake rate exhibited [NO2] dependence. However, relative to increasing [NO2], fractional uptakes decreased for BAL and 1 mM GSH but not for 10 mM GSH. 4) Altered convective gas flow produced nonlinear increments in uptake (10 mM GSH) and substantial decrements in fractional uptake. 5) Arrhenius plots [ln(r) vs. 1/T, where r is reaction rate and T is absolute temperature (degree K)] for BAL and 1 mM GSH yielded respective activation energies of 4,952 and 4,149 kcal.g-1.mol-1 and degree of change in the rate of NO2 uptake per 10 degrees C (Q10) of 1.32 and 1.25. These results imply that the rate of NO2 uptake into rat ELF, like intact lung, is limited, in part, by chemical reaction(s).(ABSTRACT TRUNCATED AT 250 WORDS)
Periodic flow at airway bifurcations. II. Flow partitioning
Authors: Tsuda A. , Kamm R. , Fredberg J. J.
Published: December 2017

The distribution of flow among parallel pathways is believed to be determined by the balance of downstream mechanical loads or time constants. We studied the influence of upstream flow conditions and airway geometry vs. downstream mechanical impedances in determining flow partitioning at airway bifurcations. Each model consisted of a single rigid bifurcation with various branching angles and area ratios but having identical pathway impedances. Sinusoidal volumetric oscillations were applied at the parent duct with various frequencies and tidal volumes. Measuring the terminal pressures continuously, we calculated the flow distribution. When flow amplitude was small, flow partitioning was homogeneous and synchronous, as expected in a system possessing homogeneous pathway impedances and time constants. But when flow amplitude was large and frequency was high, appreciable heterogeneity and asynchrony of flow partitioning arose; during midinspiration the high-velocity flow stream preferentially favored the axial pathway. This effect vanished in the absence of a net area change at the bifurcation. For a given bifurcation geometry, these observations could be organized using only two nondimensional parameters, neither of which incorporated consideration of fluid friction. The description of temporal events required, in addition, a nondimensional time. Therefore these flow-dependent phenomena and their underlying mechanisms differ fundamentally from those described in classical impedance models. The complex pattern of nonuniform interregional behaviors apparent in whole lungs when tidal volume and frequency are large (Allen et al., J. Clin. Invest. 76: 620-629, 1985) is reiterated faithfully in models consisting of only two compartments with homogeneous time constants. As such, the behaviors observed in lungs would appear to be attributable in large part to fluid dynamic factors in central airways.
Transperitoneal fluid dynamics in rabbit liver
Authors: Negrini D. , Gonano C. , Del Fabbro M. , Miserocchi G.
Published: December 2017

The peritoneal cavity of 18 anesthetized spontaneously breathing supine rabbits was opened through a midline section. One or two hollow capsules (surface area 0.8 cm2) were glued to the exposed liver surface, filled with whole or 25% diluted plasma, and connected to a transducer and a graduated pipette. Various hydraulic pressures (Pcap) were set in the capsule; at each Pcap the liquid flow per unit surface area (V/S) between the Disse's interstitial space and the capsule was measured from the rate of liquid displacement in the pipette. The slope of the V/S vs. Pcap linear regression was utilized to estimate the hydraulic conductivity of the Glissonian-peritoneal membrane and averaged 5.1 x 10(-3) +/- 4.7 x 10(-3) (SD) ml.h-1.cmH2O-1.cm-2 (n = 25). Hydraulic pressure in the Disse's space (Pd) was measured by closing the capsule against the transducer disconnected from the pipette. At portal and hepatic venous pressures of 7.6 +/- 2.9 and 2.6 +/- 1 cmH2O, respectively, Pd was 2.05 +/- 2 cmH2O. Physiologically, Starling pressure gradients cause fluid transfer from the sinusoids to the Disse's space; transperitoneal fluid filtration only occurs through the liver surface that faces the diaphragm, which corresponds to one-fifth of the total hepatic surface.
Arterial chemoreceptor input to respiratory hypoglossal motoneurons
Authors: Mifflin S. W.
Published: December 2017

To better understand the role of the arterial chemoreceptors in the regulation of upper airway patency at the level of the oropharynx, intracellular recordings were obtained from inspiratory hypoglossal motoneurons (IHMs), and the responses to selective activation of the carotid body chemoreceptors were examined. In pentobarbital-anesthetized, vagotomized, paralyzed, and artificially ventilated cats, chemoreceptor activation enhanced the inspiratory depolarization of membrane potential in 32 of 36 IHMs. This was manifested as an increase in either the amplitude (n = 13) or duration (n = 3) or an increase in both amplitude and duration (n = 16) of the inspiratory membrane potential depolarization. The amplitude and duration of the inspiratory membrane potential depolarization increased 98 +/- 15% (n = 29) and 78 +/- 13% (n = 19), respectively. Similar patterns of enhanced activity (increased duration and/or amplitude of membrane depolarization) were observed in five expiratory hypoglossal motoneurons (EHMs) after chemoreceptor activation. In 16 of the 32 IHMs, chemoreceptor activation also evoked changes in IHM membrane potential during expiration: enhanced post-inspiratory discharge (n = 6), expiratory depolarization/discharge (n = 6), and tonic depolarization/discharge, which persisted for several respiratory cycles (n = 4). The arterial chemoreceptors provide a powerful excitatory input to IHMs during both inspiration and expiration. This excitatory drive to IHMs and EHMs will aid in the maintenance of upper airway patency throughout the respiratory cycle during increases in end-tidal CO2.
Increased fatigue of isovelocity vs. isometric contractions of canine diaphragm
Authors: Ameredes B. T. , Clanton T. L.
Published: December 2017

A comparison of fatigue as a loss of force with repeated contractions over time was performed in canine respiratory muscle by isometric (nonshortening) and isovelocity (shortening) contractions. In situ diaphragm muscle strips were attached to a linear ergometer and electrically stimulated (30 or 40 Hz) via the left phrenic nerve to produce either isometric (n = 12) or isovelocity (n = 12) contractions (1.5 s) from optimal muscle length (Lo = 8.8 cm). Similar velocities of shortening between isovelocity experiments [0.19 +/- 0.02 (SD) Lo/S] were produced by maximizing the mean power output (Wmax = 210 +/- 27 mW/cm2) that could be developed over 1.5 s when displacement was approximately 0.30 Lo. Initial peak isometric tension was 1.98 kg/cm2, whereas initial peak isovelocity tension was 1.84 kg/mc2 (P less than 0.01) or 93% of initial isometric tension. Fatigue trials of 5 min were conducted on muscles contracting at a constant duty cycle (0.43). At the end of the trials, peak isovelocity tension had fallen to 50% of initial isometric tension (P less than 0.01), whereas peak isometric tension had only fallen by 27%. These results indicate that muscle shortening during force production has a significant influence on diaphragm muscle fatigue. We conclude that the effects of shortening on fatigue must be considered in models of respiratory muscle function, because these muscles typically shorten during breathing.
Late pulmonary allergic responses in actively but not passively IgE-sensitized rats
Authors: Sorkness R. , Johns K. , Castleman W. L. , Lemanske R. F.
Published: December 2017

Previous studies suggested that although rats that were passively sensitized [monoclonal murine immunoglobulin E (IgE)] would respond to pulmonary antigen challenge with an immediate increase in resistance, they exhibited no late increases in resistance, unlike late changes in rats actively sensitized to preferentially produce IgE antibody. We hypothesized that passively sensitized rats also would not develop antigen-induced pulmonary inflammation. In a blinded protocol we compared immediate responses and pulmonary resistance and inflammation at 8, 19 and 24 h after challenge with placebo antigen, with dinitrophenol-bovine serum albumin (DNP-BSA) to elicit a passively sensitized response, or with ovalbumin (OA) to elicit an actively sensitized response. Despite similar immediate responses to OA and DNP-BSA, only the rats challenged with OA had marked inflammatory changes and a significant incidence of late elevations in resistance. Inflammation scores and lung resistance were significantly correlated only in the OA group. We also observed that anesthesia with fentanyl/droperidol significantly attenuated the immediate but not the late responses to antigen challenge, compared with rats anesthetized with ketamine. We conclude that IgE-mediated immediate responses to pulmonary antigen challenge are insufficient, and may be unnecessary, to initiate antigen-induced late inflammatory changes.
Glucocorticoid-induced muscle atrophy prevention by exercise in fast-twitch fibers
Authors: Falduto M. T. , Czerwinski S. M. , Hickson R. C.
Published: December 2017

Exercise has been shown to be effective in preventing glucocorticoid-induced atrophy in muscles containing high proportions of type II or fast-twitch fibers. This investigation was undertaken to further evaluate this response in type IIa and IIb fibers, determined by histochemical staining for myofibrillar adenosinetriphosphatase with alkaline and acid preincubation. Steroid [cortisol acetate (CA), 100 mg/kg body wt] and exercise (running 90 min/day, 29 m/min) treatments were initiated simultaneously for 11 consecutive days in female rats. Fiber distribution and area measurements were performed in a deep and superficial region of plantaris muscle. The exercise regimen spared approximately 40% of the CA-induced plantaris muscle atrophy. In the deep region, the fiber population, which contained approximately 13% type I (slow-twitch), 24% type IIa, and 63% IIb fibers, was not affected by either treatment. In the superficial section, which consisted solely of type II fibers, the proportion of type IIa fibers was higher (27 vs. 9%, P less than 0.01) in the steroid- than in the vehicle-treated groups. Within each region, type IIa fibers were less susceptible to atrophy than type IIb fibers, and within each fiber type, the deep region had less atrophy than the superficial region. Type I fibers were unchanged by steroid treatment. For type IIa fibers, exercise prevented 100% of the atrophy in the deep region and 50% in the superficial region. For type IIb fibers, the activity spared 67 and 40% of the atrophy in these same regions, respectively. These results show that glucocorticoids are capable of changing the myosin phenotype.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of inspired air temperature on genioglossus activity during nose breathing in awake humans
Authors: Basner R. C. , Ringler J. , Berkowitz S. , Schwartzstein R. M. , Weinberger S. E. , Sparrow D. , Weiss J. W.
Published: December 2017

Experimental data suggest the presence of sensory receptors specific to the nasopharynx that may reflexly influence respiratory activity. To investigate the effects of inspired air temperature on upper airway dilator muscle activity during nose breathing, we compared phasic genioglossus electromyograms (EMGgg) in eight normal awake adults breathing cold dry or warm humidified air through the nose. EMGgg was measured with peroral bipolar electrodes during successive trials of cold air (less than or equal to 15 degrees C) and warm air (greater than or equal to 34 degrees C) nasal breathing and quantified for each condition as percent activity at baseline (room temperature). In four of the subjects, the protocol was repeated after topical nasal anesthesia. For all eight subjects, mean EMGgg was greater during cold air breathing than during baseline (P less than 0.005) or warm air breathing (P less than 0.01); mean EMGgg during warm air breathing was not significantly changed from baseline. Nasal anesthesia significantly decreased the mean EMGgg response to cold air breathing. Nasal airway inspiratory resistance, measured by posterior rhinomanometry in six subjects under similar conditions, was no different for cold or warm air nose breathing [cold 1.4 +/- 0.7 vs. warm 1.4 +/- 1.1 (SD) cmH2O.l-1.s at 0.4 l/s flow]. These data suggest the presence of superficially located nasal cold receptors that may reflexly influence upper airway dilating muscle activity independently of pressure changes in awake normal humans.
Hypoxic exposure and activation of the afterdischarge mechanism in conscious humans
Authors: Georgopoulos D. , Bshouty Z. , Younes M. , Anthonisen N. R.
Published: December 2017

After voluntary hyperventilation, normal humans do not develop a significant ventilatory depression despite low arterial CO2 tension, a phenomenon attributed to activation of a brain stem mechanism referred to as the "afterdischarge." Afterdischarge is one of the factors that promote ventilatory stability. It is not known whether physiological stimuli, such as hypoxia, are able to activate the afterdischarge in humans. To test this, breath-by-breath ventilation (VI) was measured in nine young adults during and immediately after a brief period (35-51 s) of acute hypoxia (end-tidal O2 tension 55 Torr). Hypoxia was terminated by switching to 100% O2 (end-tidal O2 tension of first posthypoxic breath greater than 100 Torr). Brief hypoxia increased VI and decreased end-tidal CO2 tension. In all subjects, termination of hypoxia was followed by a gradual ventilatory decay; hyperoxic VI remained higher than the normoxic baseline for several breaths and, despite the negative chemical stimulus of hyperoxia and hypocapnia, reached a new steady state without an apparent undershoot. We conclude that brief hypoxia is able to activate the afterdischarge mechanism in conscious humans. This contrasts sharply with the ventilatory undershoot that follows relief of sustained hypoxia, thereby suggesting that sustained hypoxia inactivates the afterdischarge mechanism. The present findings are of relevance to the pathogenesis of periodic breathing in a hypoxic environment. Furthermore, brief exposure to hypoxia might be useful for evaluation of the role of afterdischarge in other disorders associated with unstable breathing.
Regulation of phosphorylase a activity in human skeletal muscle
Authors: Ren J. M. , Hultman E.
Published: December 2017

The control mechanism of glycogenolysis by phosphorylase a in contracting muscle has been investigated. The quadriceps femoris muscles of six subjects were intermittently stimulated at 15 and 50 Hz. The stimulation lasted 9.6 s and was performed twice at 15 Hz and once at 50 Hz. Epinephrine was infused continuously during the experiment. The force generation and ATP turnover rate were nearly twofold higher at 50 Hz than at 15 Hz. Calculated mean Pi was 5.7 and 10.0 mM during the two 15-Hz stimulations and 8.1 mM during the 50-Hz stimulation. Phosphorylase a varied between 85.5 and 91.5% without significant differences between periods. However, the rate of glycogenolysis was twofold higher during the stimulation at 50 Hz than it was at 15 Hz (P less than 0.05) and was related to the ATP turnover rate (r = 0.992). These results demonstrate that rapid glycogen breakdown during muscle contraction cannot be solely explained by transformation of phosphorylase b to a and increased Pi concentration. The contraction intensity may determine the glycogenolytic rate through a transient increase in free AMP level related to the ATP turnover rate.
Viscoplasticity of respiratory tissues
Authors: Stamenovic D. , Glass G. M. , Barnas G. M. , Fredberg J. J.
Published: December 2017

Low-frequency mechanical behavior of various respiratory tissues shows certain similarities. In this study we test the hypothesis that rate-independent plastic processes along with rate-dependent viscoelastic processes are responsible. We considered oscillatory responses of several respiratory tissues measured over prescribed ranges of frequency (up to 6 Hz) and amplitude of forcing. These included the excised cat lung, the human chest wall in vivo, and two components of the chest wall: the excised dog rib cage and the excised rabbit abdominal viscera; some data were previously reported and some are new. We analyzed these data using the viscoplastic model of Hildebrandt (J. Appl. Physiol. 28: 365-372, 1970). It consists of three compartments: a plastoelastic compartment mechanically in parallel with a viscoelastic compartment, both in series with a lumped inertia. We fitted oscillatory data of the above respiratory tissues to the model by a least-squares technique. The fit was qualitatively consistent with the observations and exhibited moderately good to very good quantitative correspondence. As an independent verification of this approach, we obtained the stress relaxation after a step-volume change. Based on the oscillatory response of cat lungs, the calculated stress relaxation function was found to be generally consistent with corresponding observations. This study indicates that both plasticity and viscoelasticity appear to be important determinants of mechanical behavior of respiratory tissues at low frequencies and that inertial effects are negligible.
Reduced sensitivity to beta-adrenergic agonists in Basenji-Greyhound dogs
Authors: Tobias J. D. , Sauder R. A. , Hirshman C. A.
Published: December 2017

To investigate the inhibitory effects of beta-adrenergic agonists and aminophylline on pulmonary responsiveness, we evaluated the ability of albuterol and aminophylline to attenuate pulmonary responses to aerosol challenge with methacholine and histamine in intact Basenji-Greyhound (BG) and selected mongrel dogs. Pulmonary responses were measured in untreated dogs and in dogs pretreated with albuterol (1 and 2.5 micrograms/kg) or aminophylline. Before aerosol challenge, baseline pulmonary resistance (RL) and dynamic compliance (Cdyn) were not significantly different between the BGs and the mongrels. In the untreated dogs, pulmonary responses to methacholine and histamine aerosols were not different between the BGs and the mongrels. Pretreatment with albuterol (1 microgram/kg) or aminophylline significantly attenuated the pulmonary response to methacholine in the mongrels but was without effect in the BGs. Albuterol (2.5 micrograms/kg) significantly attenuated the pulmonary response to methacholine in the BGs and the mongrels; however, this attenuation was significantly greater (P less than 0.05) in the mongrels than in the BGs. In response to histamine challenge, no differences were seen between the BGs and the mongrels in the control state (no pretreatment) or after pretreatment with albuterol or aminophylline. This study demonstrates that in BGs pulmonary responsiveness to methacholine but not histamine is resistant to inhibition by beta-adrenergic agonists. This may result from a qualitative or quantitative defect in either the cholinergic or beta-adrenergic receptor or to an abnormality distal to the receptors in the signal transduction mechanism at a site where the two signals interact.
Ventilatory responses to chemoreceptor stimulation after hypoxic acclimatization in awake goats
Authors: Engwall M. J. , Bisgard G. E.
Published: December 2017

Our objective was to test the hypothesis that exposure to prolonged hypoxia results in altered responsiveness to chemoreceptor stimulation. Acclimatization to hypoxia occurs rapidly in the awake goat relative to other species. We tested the sensitivity of the central and peripheral chemoreceptors to chemical stimuli before and after 4 h of either isocapnic or poikilocapnic hypoxia (arterial PO2 40 Torr). We confirmed that arterial PCO2 decreased progressively, reaching a stable value after 4 h of hypoxic exposure (poikilocapnic group). In the isocapnic group, inspired minute ventilation increased over the same time course. Thus, acclimatization occurred in both groups. In goats, isocapnic hypoxia did not result in hyperventilation on return to normoxia, whereas poikilocapnic hypoxia did cause hyperventilation, indicating a different mechanism for acclimatization and the persistent hyperventilation on return to normoxia. Goats exposed to isocapnic hypoxia exhibited an increased slope of the CO2 response curve. Goats exposed to poikilocapnic hypoxia had no increase in slope but did exhibit a parallel leftward shift of the CO2 response curve. Neither group exhibited a significant change in response to bolus NaCN injections or dopamine infusions after prolonged hypoxia. However, both groups demonstrated a similar significant increase in the ventilatory response to subsequent acute exposure to isocapnic hypoxia. The increase in hypoxic ventilatory sensitivity, which was not dependent on the modality of hypoxic exposure (isocapnic vs. poikilocapnic), reinforces the key role of the carotid chemoreceptors in ventilatory acclimatization to hypoxia.
Geniohyoid muscle activity in normal men during wakefulness and sleep
Authors: Wiegand D. A. , Latz B. , Zwillich C. W. , Wiegand L.
Published: December 2017

Reduction in the activity of upper airway "dilator" muscles during sleep may allow the pharyngeal airway to collapse in some individuals. However, quantitative studies concerning the effect of sleep on specific upper airway muscles that may influence pharyngeal patency are sparse and inconclusive. We studied seven normal men (mean age 27, range 22-37 yr) during a single nocturnal sleep study and recorded sleep staging parameters, ventilation, and geniohyoid muscle electromyogram (EMGgh) during nasal breathing throughout the night. Anatomic landmarks for placement of intramuscular geniohyoid recording electrodes were determined from a cadaver study. These landmarks were used in percutaneous placement of wire electrodes, and raw and moving-time-averaged EMGgh activities were recorded. Sleep stage was determined using standard criteria. Stable periods of wakefulness and non-rapid-eye-movement (NREM) and rapid-eye-movement (REM) sleep were selected for analysis. The EMGgh exhibited phasic inspiratory activity during wakefulness and sleep in all subjects. In six of seven subjects, mean and peak inspiratory EMGgh activities were significant (P less than 0.05) reduced during stages 2 and 3/4 NREM sleep and REM sleep compared with wakefulness. This reduction of EMGgh activity was shown to result from a sleep-related decline in the level of tonic muscle activity. Phasic inspiratory EMGgh activity during all stages of sleep was not significantly different from that during wakefulness. Of interest, tonic, phasic, and peak EMGgh activities were not significantly reduced during REM sleep compared with any other sleep stage in any subject. In addition, the slope of onset of phasic EMGgh activity was not different during stage 2 NREM and REM sleep compared with wakefulness in these subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Stiffened erythrocytes augment the pulmonary hemodynamic response to hypoxia
Authors: Doyle M. P. , Walker B. R.
Published: December 2017

Isolated rat lungs were perfused with suspensions containing normal and stiffened erythrocytes (RBCs) during normoxic and hypoxic ventilation to assess the effect of reduced RBC deformability on the hypoxic pressor response. RBC suspensions were prepared with cells previously incubated in isotonic phosphate-buffered saline with or without 0.0125% glutaraldehyde. The washed RBCs were resuspended in isotonic bicarbonate-buffered saline (with 4% albumin) to hematocrits of approximately 35%. The lungs were perfused with control and experimental cell suspensions in succession while pulmonary arterial pressure was measured during normoxic (21% O2) and hypoxic (3% O2) ventilation. On the attainment of a peak hypoxic pressor response, flow rate was changed so that pressure-flow curves could be constructed for each suspension. RBC deformability was quantified by a filtration technique using 4.7-microns-pore filters. Glutaraldehyde treatment produced a 10% decrease in RBC deformability (P less than 0.05). Over the range of flow rates, Ppa was increased by 15-17% (P less than 0.05) and 26-31% (P less than 0.05) during normoxic and hypoxic ventilation, respectively, when stiffened cells were suspended in the perfusate. The magnitude of the hypoxic pressor response was 50-54% greater with stiffened cells over the three flow rates. In a separate set of experiments, normoxic and hypoxic arterial blood samples from conscious unrestrained rats were used to investigate the effects of acute hypoxia on RBC deformability. Deformability was measured with the same filtration technique. There was no difference in the deformability of hypoxic compared with normoxic RBCs. We conclude that the presence of stiffened RBCs enhances the hemodynamic response to hypoxia but acute hypoxia does not affect RBC deformability.
Relative effects of glycogen depletion and previous exercise on muscle force and endurance capacity
Authors: Grisdale R. K. , Jacobs I. , Cafarelli E.
Published: December 2017

Endurance capacity of human vastus lateralis muscles was observed 24 h after hard exercise followed by either a carbohydrate-restricted or a carbohydrate-loaded diet (depletion and repletion conditions). In a control condition the subjects did no previous exercise and ate their normal diet. Each of these conditions was followed by an experimental protocol in which the five male subjects made a series of alternating 25-s static contractions of each leg at 50% maximal voluntary contraction until one leg failed to achieve the required force (Tlim). Glycogen concentration before the experimental protocol in both legs was significantly lower in the depletion than in the repletion condition. Muscle lactate and creatine phosphate concentrations were within normal limits before the static contractions. The number of contractions the repleted (12.7 +/- 2.2) and depleted (10.3 +/- 1.5) legs could sustain before Tlim were not different from each other, but both were 35% (P less than 0.05) fewer than the control (17.6 +/- 3.0). Surface electromyogram (EMG) amplitude was higher in depleted than in repleted or control muscles. At Tlim, EMG amplitude was maximal, creatine phosphate was 50-70% depleted, and lactate increased fourfold. Average glycogen utilization per contraction in both the repletion and depletion conditions was 5.8 mmol/kg dry wt, but postexercise lactate concentrations were lower in depleted (14.4 +/- 3.6 mmol/kg dry wt) than in repleted (43.2 +/- 7.4) muscles. The EMG frequency distribution shifted downward in all conditions during the experimental protocol and was independent of muscle lactate concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of changes in level and pattern of breathing on the sensation of dyspnea
Authors: Chonan T. , Mulholland M. B. , Altose M. D. , Cherniack N. S.
Published: December 2017

Breathing during hypercapnia is determined by reflex mechanisms but may also be influenced by respiratory sensations. The present study examined the effects of voluntary changes in level and pattern of breathing on the sensation of dyspnea at a constant level of chemical drive. Studies were carried out in 15 normal male subjects during steady-state hypercapnia at an end-tidal PCO2 of 50 Torr. The intensity of dyspnea was rated on a Borg category scale. In one experiment (n = 8), the level of ventilation was increased or decreased from the spontaneously adopted level (Vspont). In another experiment (n = 9), the minute ventilation was maintained at the level spontaneously adopted at PCO2 of 50 Torr and breathing frequency was increased or decreased from the spontaneously adopted level (fspont) with reciprocal changes in tidal volume. The intensity of dyspnea (expressed as percentage of the spontaneous breathing level) correlated with ventilation (% Vspont) negatively at levels below Vspont (r = -0.70, P less than 0.001) and positively above Vspont (r = 0.80, P less than 0.001). At a constant level of ventilation, the intensity of dyspnea correlated with breathing frequency (% fspont) negatively at levels below fspont (r = -0.69, P less than 0.001) and positively at levels above fspont (r = 0.75, P less than 0.001). These results indicate that dyspnea intensifies when the level or pattern of breathing is voluntarily changed from the spontaneously adopted level. This is consistent with the possibility that ventilatory responses to changes in chemical drive may be regulated in part to minimize the sensations of respiratory effort and discomfort.