bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional and structural changes with hypoxia in pulmonary circulation of spontaneously hypertensive rats
Authors: Janssens S. P. , Thompson B. T. , Spence C. R. , Hales C. A.
Published: December 2017

Chronic hypoxic pulmonary hypertension involves both vasoconstriction and vascular remodeling. Spontaneously hypertensive rats (SHR) have an increased systemic vascular resistance and a greater responsiveness to constricting stimuli. We hypothesized that, in contrast to age-matched normotensive Wistar-Kyoto rats (WKY), SHR also display spontaneous pulmonary hypertension in normoxia and increased vascular response to acute and chronic hypoxia. Baseline mean pulmonary arterial pressure (PAP) and total pulmonary resistance (TPR) were higher in SHR than in WKY. With acute hypoxia (10% O2 for 15 min), PAP increased to the same extent in SHR and WKY and cardiac output (CO) was unchanged in WKY but increased in SHR. Thus, the rise in PAP in the SHR might be accounted for by the rise in CO, as TPR did not rise, but not that in the WKY, as TPR increased. After 12 days in hypoxia (10% O2), mean arterial pressure was unchanged in WKY but decreased significantly in SHR without a change in CO. PAP increased by 59% in SHR and 54% in WKY when the rats were taken from the hypoxic chamber for 1 h. Acute hypoxic challenge caused a further increase in PAP only in WKY. Medial wall thickness of alveolar duct and terminal bronchial vessels was similar in WKY and SHR after chronic hypoxia. We conclude that SHR exhibit mild baseline pulmonary hypertension in normoxia and that chronic hypoxia does not produce a disproportionate increase in SHR pulmonary vascular remodeling and pulmonary hypertension.
Influence of nonlinearities on estimates of respiratory mechanics using multilinear regression analysis
Authors: Kano S. , Lanteri C. J. , Duncan A. W. , Sly P. D.
Published: December 2017

To investigate the influence of nonlinearities on estimates of respiratory mechanics, differing patterns of mechanical ventilation patterns were analyzed from 8 puppies and 14 children. Respiratory mechanics were calculated using multiple linear regression to fit a linear single-compartment model, a volume-dependent single-compartment model (VDSCM), and a flow-dependent single-compartment model. The ratio of the compliance of the last 20% of the dynamic volume-pressure (V-P) curve to the total compliance (C20/C) and the contribution of a volume-dependent elastance to total elastance [%E2 = E2 (VT)/[(E1 + E2)VT], where E1 + E2 is total elastance, E2 is the volume-dependent component, and VT is tidal volume] were used as the indexes of over-distension. By positioning the dynamic loops on the static V-P curves, ventilation patterns were classified as overdistended or nonoverdistended. In the overdistended group, the C20/C was significantly lower (0.71 +/- 0.10 vs. 0.92 +/- 0.16; P < 0.0001) and %E2 was significantly higher (43.4 +/- 15.0 vs. 0.51 +/- 18.02%, P < 0.0001) than in the nonoverdistended group. The mode of ventilation (pressure controlled vs. volume controlled) and the resistive pressures that resulted in widening of the dynamic V-P loop were found to alter C20/C but not %E2. When the respiratory system was overdistended, i.e., ventilated up to the flattened portion of the V-P curve, the VDSCM gave more accurate estimates of respiratory mechanisms. Furthermore, %E2 calculated from VDSCM is a useful parameter for estimating respiratory system overdistension that is not affected by resistive pressures.
Permeability of ferret trachea in vitro to 99mTc-DTPA and [14C]antipyrine
Authors: Hanafi Z. , Webber S. E. , Widdicombe J. G.
Published: December 2017

Platelet-activating factor (PAF) and vasoactive drugs were tested on permeability of ferret trachea in vitro by measuring fluxes of 99mTc-diethylenetriamine pentaacetic acid (99mTc-DTPA; hydrophilic) and [14C]antipyrine ([14C]AP; lipophilic) across the tracheal wall. Tracheae were bathed on both sides with Krebs-Henseleit buffer, with luminal buffer containing either 99mTc-DTPA or [14C]AP. Luminal and abluminal radioactivities, potential difference, and tracheal smooth muscle tone were measured. Baseline 99mTc-DTPA and [14C]AP permeability coefficients were -4.7 +/- 0.6 (SE) x 10(-7) and -2.2 +/- 0.1 x 10(-5) cm/s, respectively. PAF (10 microM) increased permeability to 99mTc-DTPA to -35.3 +/- 7.6 x 10(-7) cm/s (P < 0.05), but permeability to [14C]AP did not change, suggesting that paracellular but not transcellular transport was affected. Abluminal and luminal applications of methacholine (MCh, 20 microM), phenylephrine (PE, 100 microM), and albuterol (Alb, 100 microM) caused no change in permeability to 99mTc-DTPA before or after exposure to luminal PAF, but abluminal histamine (Hist, 10 microM) significantly increased permeability. Abluminal Hist decreased permeability to [14C]AP before and after exposure to PAF. MCh, PE, and Hist increased smooth muscle tone; Alb and PAF had no effect. Thus, only PAF and Hist altered permeability to 99mTc-DTPA, and MCh, PE, and Hist changed smooth muscle tone. Tracheal permeability changes were greater for the hydrophilic than for the lipophilic agent.
Effect of enhanced supramaximal flows on cough clearance
Authors: Bennett W. D. , Zeman K. L.
Published: December 2017

Efficiency of cough for clearing mucus from the lungs is believed to be a function of peak airflow velocities in the airways. Initial transient supramaximal flows are characteristic of cough, and these peak flow rates can be enhanced by placing a triggered shutter at the mouth, serving the role of the epiglottis. Using radiolabeled monodispersed aerosols (99mTc-iron oxide) and gamma camera analysis, we measured over a 2-h period the efficacy of 60 voluntary vs. shutter coughs for clearing mucus from the airways of patients (n = 15) with chronic airway obstruction (mean ratio of forced expired volume in 1 s to forced vital capacity = 0.55). In a subset of patients (n = 9), we also measured the efficacy of forced expirations, or huffs, without glottis closure. Peak flow rate was greater for shutter than voluntary coughs [9.4 +/- 2.0 (SD) vs. 4.1 +/- 1.9 l/s; P < 0.001]. Retention at 60 min (as a fraction of initial deposition) was significantly different for the 3 study days (control, 0.83 +/- 0.17; voluntary cough, 0.69 +/- 0.18; shutter cough, 0.75 +/- 0.19; P = 0.01), but only control vs. voluntary cough values were significantly different from each other (P = 0.01). In contrast, retention at 120 min was significantly different for the 3 days, but both voluntary and shutter coughs were significantly different from control (P = 0.01 and P = 0.02, respectively) (control, 0.73 +/- 0.16; voluntary cough, 0.61 +/- 0.20; shutter cough, 0.65 +/- 0.20). Patients studied with buffs showed a clearance rate faster than control and similar to that associated with voluntary cough.(ABSTRACT TRUNCATED AT 250 WORDS)
Analysis of factors affecting gas exchange in intravascular blood gas exchanger
Authors: Niranjan S. C. , Clark J. W. , San K. Y. , Zwischenberger J. B. , Bidani A.
Published: December 2017

A mathematical model of an intravascular hollow-fiber gas-exchange device, called IVOX, has been developed using a Krogh cylinder-like approach with a repeating unit structure comprised of a single fiber with gas flowing through its lumen surrounded by a coaxial cylinder of blood flowing in the opposite direction. Species mass balances on O2 and CO2 result in a nonlinear coupled set of convective-diffusion parabolic partial differential equations that are solved numerically using an alternating-direction implicit finite-difference method. Computed results indicated the presence of a large resistance to gas transport on the external (blood) side of the hollow-fiber exchanger. Increasing gas flow through the device favored CO2 removal from but not O2 addition to blood. Increasing blood flow over the device favored both CO2 removal as well as O2 addition. The rate of CO2 removal increased linearly with the transmural PCO2 gradient imposed across the device. The effect of fiber crimping on blood phase mass transfer resistance was evaluated indirectly by varying species blood diffusivity. Computed results indicated that CO2 excretion by IVOX can be significantly enhanced with improved bulk mixing of vena caval blood around the IVOX fibers.
Voluntary exercise decreases progression of muscular dystrophy in diaphragm of mdx mice
Authors: Dupont-Versteegden E. E. , McCarter R. J. , Katz M. S.
Published: December 2017

Effects of voluntary wheel running on contractile properties of diaphragm (DIA) and soleus (SOL) of dystrophic (mdx) and control (C57BL/10SNJ) mice were evaluated. In particular, we tested the hypothesis that daily voluntary running is not deleterious to muscle function in mdx mice. Both groups of mice ran extensively (control mice approximately 7 km/day, mdx mice approximately 5 km/day). Exercise increased maximal specific tetanus tension of mdx DIA from 1.02 +/- 0.04 to 1.33 +/- 0.06 kg/cm2 but did not restore it to the control level (2.55 +/- 0.17 kg/cm2). Maximal tetanus tension of sedentary mdx SOL (2.41 +/- 0.17 kg/cm2) was reduced compared with control (3.10 +/- 0.15 kg/cm2) and was not altered by running activity. Optimal length was significantly lower in DIA of mdx mice, and exercise did not change this. Fatigability and contractile properties of muscles measured in vitro were not altered by running activity with the exception of increased contraction time in mdx DIA. In conclusion, extensive wheel running is not deleterious to muscle function in mdx mice contrary to predictions of the “work overload” theory of muscular dystrophy. Rather, this exercise is beneficial for active tension generation of mdx DIA, the muscle most closely resembling muscles of patients with Duchenne muscular dystrophy.
Lung function, surfactant apoprotein content, and level of PEEP in prematurely delivered rabbits
Authors: Ogawa A. , Brown C. L. , Schlueter M. A. , Benson B. J. , Clements J. A. , Hawgood S.
Published: December 2017

To study the in vivo activity of the surfactant apoproteins (SP-A, SP-B, SP-C), we administered surfactants with defined apoprotein compositions to prematurely delivered rabbit pups. Rabbits given simple phospholipid mixtures containing dipalmitoylphosphatidylcholine and phosphatidylglycerol supplemented with both SP-B and SP-C or either protein alone had significantly greater lung compliance during ventilation and lung expansion during a quasi-static pressure-volume maneuver than did saline-or lipid-treated controls. The response to the surfactants containing SP-B/C was markedly dependent on the level of end-expiratory pressure used during ventilation. When the rabbits were ventilated with a positive end-expiratory pressure (PEEP) of 4 cmH2O, lung function in the pups treated with SP-B/C was not significantly different from rabbit surfactant-treated controls. Addition of SP-A to the surfactants containing SP-B/C did not significantly further improve lung function if the pups were ventilated with a PEEP of 4 cmH2O. With a lower PEEP of 1 cmH2O, lung function in the pups given surfactants containing SP-B/C was no longer equivalent to the lung function of the rabbit surfactant-treated controls. At the lower PEEP, SP-A significantly improved lung function when it was added to surfactants containing SP-B and SP-C. No beneficial effect of SP-A was seen when the surfactant contained either SP-B or SP-C alone. We conclude that with assisted ventilation that includes a moderate level of PEEP, SP-B and SP-C significantly enhance the effect of a simple phospholipid mixture on the lung function of prematurely delivered rabbits. At lower levels of PEEP the effects of SP-B and SP-C on lung function are markedly reduced but can be restored by the addition of SP-A. Our results are consistent with the existence of cooperative protein-protein interactions in surfactant function in vivo and suggest that the response to a surfactant will be determined by both the ventilation strategy and the surfactant composition. composition.
Prediction of central nervous system oxygen toxicity in rats
Authors: Arieli R. , Hershko G.
Published: December 2017

Cumulative O2 toxicity (K) can be calculated using the expression K = t2 x PO2c, where t is exposure time and the power c is to be determined; the phenomenon is liable to occur when K reaches Kc, the threshold value of K at which a symptom is manifested. Six rats were each exposed six times to 6 ATA O2 at 2-day intervals until the first electrical discharge (FED) was noted in an electroencephalogram. There was no difference in latency to FED in the series of six exposures. Thirteen rats were exposed to O2 until FED was noted in an electroencephalogram. They were exposed to four constant PO2's of 5, 6, 7, and 8 ATA and to two combined profiles of 1) 5 min at 7 ATA followed by 5 ATA and 2) 15 min at 5 ATA followed by 7 ATA. The solution of the equation for each rat was used to predict its latency to FED on the combined profile. The correlation of predicted to measured latency was significant (P < 0.0001), and the slope was not different from 1. Solving for these parameters using the combination of all the data, we obtained Kc = 5.71 x 10(6) and c = 5.39, which correctly predicted the mean latency but failed to predict individual latency. It is preferable to use each rat as its own control. The significance of the correlation supports the validity of the power equation for calculating K.
Acidosis stimulates beta-endorphin release during exercise
Authors: Taylor D. V. , Boyajian J. G. , James N. , Woods D. , Chicz-Demet A. , Wilson A. F. , Sandman C. A.
Published: December 2017

Elevated blood levels of beta-endorphin have been associated with high-intensity exertion, but the stimulus for beta-endorphin release is unknown. Some studies of exercise have associated beta-endorphin release with increased exertion levels, but other evidence suggests that acidosis may stimulate the release of beta-endorphin. This study examines acidosis as a possible stimulus for beta-endorphin release by examining the effects of arterial blood gases, whole blood lactate, and respiratory changes on beta-endorphin levels and by examining the effects of buffering during exercise on these levels. Initially, seven healthy adult males were evaluated during incremental exercise. During incremental exertion, indicators of acidosis correlated with endorphin levels: pH (r = -0.94), PCO2 (r = -0.85), HCO3- (r = -0.88), base excess (r = -0.94), and lactate (r = 0.89). A multivariate model showed that beta-endorphin levels were predicted best by the change in base excess. A time course analysis showed that beta-endorphin responses peaked postexercise and paralleled blood acid levels. Subsequently, subjects were compared after alkali loading and placebo during constant-intensity exercise at 85% of maximal exertion to determine whether acidosis is necessary for endorphin release. Treatment with a buffer, which effectively maintained pH above 7.40, significantly suppressed endorphin release (F = 3.07; P < 0.0001). The results of this study indicate that acidosis rather than any other physiological change associated with high-intensity exertion is the primary stimulus for beta-endorphin release.
Lung parenchyma and type II cell morphometrics: effect of surfactant treatment on preterm ventilated lamb lungs
Authors: Pinkerton K. E. , Lewis J. F. , Rider E. D. , Peake J. , Chen W. , Madl A. K. , Luu R. H. , Ikegami M. , Jobe A. H.
Published: December 2017

The effect of exogenous surfactant treatment on lung and type II cell structure of ventilated lambs of 137–138 days gestational age was studied. Thirty-four lambs were delivered and randomized to control or 100 mg/kg of natural sheep surfactant treatment groups. Lungs from one group of lambs not treated with surfactant were fixed before ventilation, and the other animals were ventilated to maintain normal blood gas values for 3, 24, or 48 h. Morphometric assessment of the inflation-fixed lung parenchyma of ventilated lungs was compared with the architectural appearance of alveoli and alveolar ducts in the unventilated lungs. Mechanical ventilation resulted in distension of alveolar ducts accompanied by the shallowing and loss of well-defined alveoli and areas of atelectasis at 3 h. These abnormalities increased in severity after 24 and 48 h of ventilation. Surfactant treatment before ventilation significantly reduced the extent and degree of dilatation and concomitant atelectasis. The fraction of normal parenchyma was 38 +/- 7% in untreated lambs vs. 64 +/- 6% in treated lambs after 24 h of ventilation. After 48 h of ventilation, significant differences between control (39 +/- 6%) and surfactant-treated (55 +/- 6%) lambs were still evident. Alveolar type II cells contained approximately 15% lamellar bodies by volume. Neither surfactant treatment nor time of ventilation altered the volume density of lamellar bodies or other organelles, except for a decrease in glycogen from 8% in nonventilated lungs to 2.5% in lungs ventilated for 24 h. These findings indicate that a surfactant treatment at birth results in the maintenance of more normal parenchyma with less atelectasis during prolonged ventilation of the immature lung.(ABSTRACT TRUNCATED AT 250 WORDS)
Ergometric studies of untrained skeletal muscle demonstrate feasibility of muscle-powered cardiac assistance
Authors: Trumble D. R. , Magovern J. A.
Published: December 2017

The feasibility of biomechanical circulatory assistance hinges on the capacity of skeletal muscle to generate significant hemodynamic work. This study quantifies linear contractile energetics via a customized hydraulic ergometer. Six normal canine latissimus dorsi (LD) muscles (200 +/- 25 g) were evaluated. The muscles were not mobilized; thereby their collateral circulation was preserved. The humeral insertion of the LD muscle was transected and connected to the ergometer. Preload was adjusted to return the LD muscle to its in situ length, and one pulse train was delivered every second. The resulting contractions generated peak pressures of 134 +/- 17 mmHg with mean pressures during shortening of 102 +/- 12 mmHg. Flow rates averaged 5.45 +/- 0.26 l/min. Mechanical work output was calculated at 1.14 +/- 0.18 J/contraction, yielding an average power production of 4.57 +/- 0.72 W during shortening. Continuous LD output power, measured at 5.76 +/- 0.90 mW/g, compares favorably with the 3.48 mW/g typically generated by a 350-g human heart. We therefore conclude that skeletal muscle of sufficient mass can sustain work rates suitable for cardiac assistance despite the 50% power losses typically experienced after muscle training.
Vagal input enhances responsiveness of respiratory discharge to central changes in pH/CO2 in bullfrogs
Authors: Kinkead R. , Filmyer W. G. , Mitchell G. S. , Milsom W. K.
Published: December 2017

This study investigated the interaction between vagal afferent input and central chemosensitivity in modulating the respiratory motor output of in vitro brain stem-spinal cord preparations from adult bullfrogs. With this preparation, the spatiotemporal distribution of respiratory-related motor output emulated that of intact bullfrogs; that is, the fictive breathing pattern was mostly episodic. Recordings from cranial motor nerves (V and X) showed that, without peripheral feedback, increasing the PCO2 of the mock cerebrospinal fluid (thereby reducing pH from 8.3 to 7.7) caused a modest increase in respiration-related burst frequency. When the pulmonary branch of a vagus nerve was stimulated phasically (2 V, 20 Hz, 0.2 ms) during each fictive breath to simulate afferent pulmonary stretch receptor feedback 1) the responsiveness of the preparation to the same changes in pH was augmented nearly threefold and 2) the breathing pattern remained episodic. It appears, therefore, that episodic breathing is an intrinsic property of the central nervous system in bullfrogs. It is concluded that there is a strong interaction between vagal feedback and central chemodetection in controlling the temporal relationships that characterize this episodic breathing pattern.
Failure of hemoconcentration during standing to reveal plasma volume decline induced in the erect posture
Authors: Lundvall J. , Bjerkhoel P.
Published: December 2017

The hypothesis was tested that the hemoconcentration observed during standing provides erroneous information about the induced plasma volume (PV) decline. Male volunteers (n = 10) stood quietly for 15 min after supine rest. On standing arterial hemoglobin (Hb) rose slowly to reach an increase of 5.9 +/- 0.3% (SE) after 15 min. Early after resuming the supine position, Hb increased further to 9.2 +/- 0.5% above control level and then declined gradually. Venous antecubital blood from the left arm supported horizontally at heart level in both the supine and standing positions (no hydrostatic load) showed very similar changes. However, Hb in venous blood collected during standing from the right arm held in the natural dependent position rose much more markedly than that in arterial blood and in venous blood from the horizontal arm (470 +/- 122, 105 +/- 24, and 55 +/- 7% greater increase at 5, 10, and 15 min, respectively). Taken together, these observations indicated that 1) analyses of arterial blood sampled from the standing subject grossly underestimated the prevailing “overall” hemoconcentration and PV decline, a phenomenon ascribed to incomplete mixing of blood between dependent and nondependent regions; 2) arterial blood sampled from the recumbent subject early (60 s) after completion of standing reflected the “true” overall intravascular hemoconcentration, with a calculated PV decline of no less than 511 +/- 27 ml, because the supine position facilitated proper mixing of blood between circulatory compartments; 3) data from common venous sampling from the dependent arm during standing primarily reflected a regional hemoconcentration (fluid loss) in the arm rather than PV decline; and 4) short-term quiet standing caused a more prominent and hemodynamically important decrease in PV than usually believed.
Metabolic characteristics of primary inspiratory and expiratory muscles in the dog
Authors: Powers S. K. , Farkas G. A. , Criswell D. , Herb R. A. , Zambito K. , Dodd S.
Published: December 2017

These experiments examined the metabolic properties of the canine respiratory muscles. Because the costal diaphragm (COD), crural diaphragm (CRD), parasternal intercostals (PI), triangularis sterni (TS), and transversus abdominis (TA) are active during quite breathing in the dog, we hypothesized that these muscles would have different metabolic profiles (i.e., higher oxidative and antioxidant enzyme activities) compared with ventilatory muscles recruited only at increased ventilatory requirements [e.g., scalene (SC) and external oblique (EO)] and locomotor muscles [e.g., deltoid (DEL)]. To test this hypothesis, muscle samples were removed from six healthy adult dogs and analyzed to determine the activities of citrate synthase (CS), phosphofructokinase (PFK), 3-hydroxyacyl-CoA dehydrogenase (HADH), and superoxide dismutase (SOD). The activities of these enzymes were interpreted as relative measures of metabolic capacities, and enzyme activity ratios were considered as representing relationships between different metabolic pathways. Analysis revealed that CS and HADH activities were significantly higher (P < 0.05) in the PI, COD, CRD, and TS compared with those in all other muscles. Muscles with the lowest CS, HADH, and SOD activities (i.e., SC, TA, EO, DEL) generally had the highest PFK activities, Furthermore, the PFK/CS ratio was significantly lower in the PI, COD, CRD, and TS compared with that in all other muscles studied. These data support the notion that the canine PI, COD, CRD, and TS are metabolically different from other key ventilatory muscles.
Skeletal muscle pH assessed by biochemical and 31P-MRS methods during exercise and recovery in men
Authors: Sullivan M. J. , Saltin B. , Negro-Vilar R. , Duscha B. D. , Charles H. C.
Published: December 2017

The present study was designed to compare evaluation of skeletal muscle metabolism (vastus lateralis) evaluated by 31P-magnetic resonance spectroscopy (MRS) and biochemical analysis. During identical isometric knee extensor exercise protocols to fatigue in eight men, biopsy samples were taken at rest, peak exercise, and 32 s postexercise and 31P-MRS data were collected continuously for phosphocreatine (PCr), pH, ATP, and P(i) at 8- or 32-s intervals. There was no difference in ATP or pH measurements between the two techniques at rest, during peak exercise, or in recovery. Corresponding measurements of pH by the two techniques were closely related (r = 0.88, P < 0.01), and pH measured by 31P-MRS was closely related to muscle lactate accumulation (r = -0.84, P < 0.001). The level of PCr at peak exercise, expressed as a percentage of the baseline value, was not different between the two techniques (42 +/- 15 vs. 46 +/- 15%). The results indicate that, in skeletal muscle in normal subjects, 1) measurements of pH and PCr at rest and during exercise do not differ between the 31P-MRS and biopsy techniques and 2) muscle pH measured by 31P-MRS is closely related to lactate accumulation in men. Our data suggest that direct comparison of results of studies of exercise metabolism using these two techniques is warranted.
Effects of acute and chronic maternal exercise on fetal heart rate
Authors: Webb K. A. , Wolfe L. A. , McGrath M. J.
Published: December 2017

Maternal-fetal effects of cycle ergometer conditioning (heart rate of 145 beats/min at 25 min/day for 3 days/wk) were studied during the second and third pregnancy trimesters. Subjects were 22 previously sedentary women and 16 nonexercising pregnant control women. Fetal heart rate (FHR) characteristics were studied before, during, and after 15 min of upright cycling at a maternal heart rate target of 145 beats/min at the end of both the second and third trimesters. Despite higher cycling power outputs in the exercised group, mean FHR responses were similar in both groups and conformed to 1) gradual increase in FHR baseline during exercise, 2) normal variability, and 3) normal reactivity. Fetal bradycardia was observed during (n = 1) and after (n = 2) exercise in three isolated tests. The timing of these events suggested that the likelihood of significant fetal hypoxia is highest in the immediate postexercise period. These results also support the hypothesis that physically conditioned women can perform at higher exercise power outputs than sedentary women without inducing fetal hypoxic stress. Further study is recommended to examine possible fetal and placental adaptations to maternal aerobic conditioning.
Pulmonary interstitial pressure in anesthetized paralyzed newborn rabbits
Authors: Miserocchi G. , Poskurica B. H. , Del Fabbro M.
Published: December 2017

In anesthetized paralyzed term newborn rabbits at various postgestational ages (from birth up to 16 days), we measured by micropuncture technique the hydraulic pressure of the pulmonary interstitium (Pip), the extrapleural parietal interstitium, and the pleural liquid. Birth data refer to cesarian-delivered nonbreathing rabbits. Pip increased from 0.5 +/- 2 to 6 +/- 0.7 cmH2O from birth up to 2 h and then decreased, becoming subatmospheric at 5 h and attaining -6 +/- 1.6 cmH2O at 16 days. Over the same period of time, pressure in the extrapleural parietal interstitium and the pleural liquid remained fairly constant at an average value of approximately -1.5 and -2 cmH2O, respectively. The wet-to-dry weight ratio of the lungs decreased from 7.8 +/- 0.4 to 4.9 +/- 0.1 at 16 days. Plasma protein concentration was 4.2 +/- 0.4 g/dl at birth, decreased to 3.2 +/- 0.5 g/dl at 1 h from delivery, and increased back to 4 +/- 0.6 g/dl at 16 days. Pleural liquid protein concentration was 3 +/- 0.1 g/dl at birth and decreased to 1.2 +/- 0.2 g/dl at 16 days. In the first hours of postnatal life, the marked increase in Pip appears to be a key factor in favoring fluid clearance from pulmonary interstitium into the pulmonary capillaries and the pleural space. This factor vanishes after approximately 6 h because of the marked decrease in Pip.
Osmolality alters tracheal blood flow and tracer uptake in anesthetized sheep
Authors: Wells U. M. , Hanafi Z. , Widdicombe J. G.
Published: December 2017

Changes in the osmolality of airway surface liquid cause bronchoconstriction, mucus secretion, and ion transport, but little is known about the effects on the permeability of the trachea to drugs applied to the tracheal lumen. Using the anesthetized sheep, we have investigated the effects of hyperosmolar (725 +/- 11 mosmol/kg) and hyposmolar (128 +/- 5 mosmol/kg) Krebs-Henseleit (KH) solution in the tracheal lumen (mean volume 13.6 ml) on the uptake of technetium-99m-labeled diethylenetriamine pentaacetic acid (99mTc-DTPA), a low-molecular-mass hydrophilic tracer that is thought to cross the epithelium via paracellular pathways, and on blood flow. All changes in osmolality were made by altering the NaCl content. We perfused a tracheal artery and collected tracheal venous blood. Hyperosmolar KH increased water movement into the lumen (+2.0 ml) and solute flux out of the lumen. It increased arterial (+24.5%) and venous (+20.6%) flows and decreased 99mTc-DTPA concentration (-26.3%) and output (-12.0%) in venous blood. Hyposmolar KH caused water movement out of the lumen (-0.9 ml) and solute flux into the lumen. It had no effect on arterial (+0.6%) and venous (+5.5%) flows and greatly increased the concentration (+345%) and output (+375%) of 99mTc-DTPA in venous blood. The baseline permeability coefficient for 99mTc-DTPA (-9.1 x 10(-7) cm/s) was not affected by hyperosmolar KH (-8.7 x 10(-7) cm/s) but was increased by hyposmolar KH (-21.4 x 10(-7) cm/s). These results confirm that hyperosmolar liquid in the lumen increases blood flow and indicate that tracer uptake is affected by the bulk flow of water across the airway wall.
Restricted postexercise pulmonary diffusion capacity does not impair maximal transport for O2
Authors: Hanel B. , Clifford P. S. , Secher N. H.
Published: December 2017

We evaluated whether the postexercise reduction of pulmonary diffusion capacity for carbon monoxide (DLco) is influenced by a second bout of rowing and whether it affects arterial O2 tension during maximal exercise. After exercise, DLco was reduced [from a median of 37 (range of 30–44) to 34 (27–40) ml.min-1.mmHg-1; n = 21; P < 0.001], and both the membrane diffusion capacity [from 80 (58–139) to 68 (54–104) ml.min-1.mmHg-1] and the pulmonary capillary blood volume [from 88 (74–119) to 79 (61–121) ml; P < 0.01] were affected. A second bout of exercise did not influence DLco or membrane diffusion capacity (n = 7), but during both bouts arterial O2 tension was reduced [from 105 (91–110) to 91 (77–102) Torr; P < 0.001] and arterial O2 saturation decreased [from 0.98 (0.97–0.99) to 0.95 (0.86––0.96); P < 0.001]. Furosemide (iv) did not affect DLco (n = 7), suggesting that it was influenced by the central blood volume rather than by pulmonary edema.
Microvascular responses to body tilt in cutaneous maximus muscle of conscious rats
Authors: Puri R. K. , Segal S. S.
Published: December 2017

We investigated microvascular responses to head-up tilt (HUT) and head-down tilt (HDT) in striated muscle of conscious male rats (n = 15; body wt 163 +/- 5 g). To observe the microcirculation in the cutaneous maximus muscle, a transparent polycarbonate chamber (1.5 cm diam) was implanted aseptically into a skin fold created between the shoulders. Rats were trained to sit quietly during HUT and HDT while positioned on a horizontal microscope that rotated in the sagittal plane. At 4–5 days after surgery, arteriole and venule diameters were recorded using videomicroscopy while the rat experienced 10 min each (in random order) of HUT or HDT at 20 degrees or 40 degrees separated by 2-h rest periods. HUT had no affect on microvessel diameter; 20 degrees HDT had little affect. In response to 40 degrees HDT, “large” arterioles (88 +/- 18 microns; n = 10) constricted by 18 +/- 2% (P < 0.05) and “small” arterioles (40 +/- 17 microns; n = 7) dilated by 21 +/- 3% (P < 0.05); this difference suggests variation in mechanisms controlling arteriolar responses. Venules (45 +/- 22 microns; n = 9) exhibited a larger fluctuation in diameter (amplitude 13 +/- 5 microns) during 40 degrees HDT compared with other body positions (amplitude typically 2–3 microns), suggesting that venomotor activity may be induced with sufficient fluid shift or change in central venous pressure. These observations illustrate a viable model for studying microvascular responses to gravitational stress in conscious rats.
Hyperinflation with intrinsic PEEP and respiratory muscle blood flow
Authors: Kawagoe Y. , Permutt S. , Fessler H. E.
Published: December 2017

Increased end-expiratory lung volume and intrinsic positive end-expiratory pressure (PEEP) are common in obstructive lung disease, especially during exacerbations or exercise. This loads the respiratory muscles and may also stress the circulatory system, causing a reduction or redistribution of cardiac output. We measured the blood flow to respiratory muscles and systemic organs using colored microspheres in 10 spontaneously breathing anesthetized tracheotomized dogs. Flows during baseline breathing (BL) were compared with those during hyperinflation (HI) induced by a mechanical analogue of airway closure and with those during an inspiratory resistive load (IR) that produced an equivalent increase in inspiratory work and time-integrated transdiaphragmatic pressure. Cardiac output was unchanged during IR (3.19 +/- 0.27 l/min at BL, 3.09 +/- 0.34 l/min during IR) but was reduced during HI (2.14 +/- 0.29 l/min; P < 0.01). Among the organs studied, flow was unaltered by IR but decreased to the liver and pancreas and increased to the brain during HI. For the respiratory muscles, flow to the diaphragm increased during IR. However, despite a 1.9-fold increase in inspiratory work per minute and a 2.5-fold increase in integrated transdiaphragmatic pressure during HI, blood flow to the diaphragm was unchanged and flow to the scalenes and sternomastoid fell. The only respiratory muscle to which flow increased during HI was the transversus abdominis, an expiratory muscle. We conclude that the circulatory effects of hyperinflation in this model impair inspiratory muscle perfusion and speculate that this may contribute to respiratory muscle dysfunction in hyperinflated states.
Geometry of respiratory phase switching
Authors: Sammon M.
Published: December 2017

A second-order ordinary differential equation is outlined for the temporal dynamics of the respiratory central pattern generator (RCPG). Recurrent interactions between central excitation and inhibition confine the breathing cycle to the interior of a heteroclinic orbit between switching points (saddle equilibria) located at end expiration (E-I) and end inspiration (I-E). Dynamics depend on four eigenvalues that control inspiratory drive (lambda), excitability of inspiratory off switch (omega 1; stage 1 expiration), rate of central excitation disinhibition (omega 2; stage 2 expiration), and damping of the oscillator (epsilon). Ratios omega 2/lambda and omega 1/lambda determine local E-I and I-E phase switching, whereas inspiratory-to-expiratory balance varies as omega 2/(lambda omega 1). Stable apnea is seen when (lambda omega 2)/epsilon is near zero; inspiratory apneusis is seen when (lambda omega 1)/epsilon is low. The equations provide formalisms for discussing phase switching, apneas, apneuses, phase resetting and singularities, rapid shallow breathing, postinhibitory rebound excitation, redundancy, gating within the RCPG, and behavioral control of breathing. The model is offered as an explicit alternative to the harmonic oscillator models that have been used in the past to describe RCPG function.
Beta-adrenergic effects on left ventricular filling: influence of aging and exercise training
Authors: Stratton J. R. , Levy W. C. , Schwartz R. S. , Abrass I. B. , Cerqueira M. D.
Published: December 2017

Reduced heart rate and contractile responses to beta-agonist stimulation characterize normal cardiac aging, but whether diastolic responses also decline with aging has not been determined in humans. Diastolic filling responses to isoproterenol were determined in 13 older (60–82 yr) and 11 young (24–32 yr) healthy men before and after endurance training. Filling rates were expressed in three ways: 1) normalized to end-diastolic volume per second, 2) normalized to stroke volume per second, and 3) as absolute milliliters of blood (ml.s-1.m-2). Peak early filling rates by all methods were reduced at rest and all isoproterenol doses with aging (all P < 0.0001 for old vs. young), whereas peak atrial filling rates were increased with aging. During isoproterenol, both peak early and peak atrial filling rates increased significantly (all P < 0.01); the increase in filling rates with isoproterenol was not different with aging (all NS for old vs. young x dose). Endurance training did not augment diastolic filling responses to isoproterenol. Although diastolic filling rates at rest are markedly altered by aging, diastolic filling responses to isoproterenol are not reduced with aging. Thus the age-associated declines in heart rate, ejection fraction, and cardiac output responses to beta-adrenergic stimulation with isoproterenol do not extend to diastolic filling responses.
Pulmonary congestion enhances responses of lung rapidly adapting receptors to cigarette smoke in rabbit
Authors: Ravi K. , Kappagoda C. T. , Bonham A. C.
Published: December 2017

We examined the effects of low-nicotine cigarette smoke, pulmonary venous congestion, and their combination on the activity of rapidly (RAR) and slowly adapting receptors (SAR) in anesthetized rabbits. Pulmonary venous congestion was achieved by inflating a balloon in the left atrium to increase left atrial pressure. We examined smoke effects on RARs (averaged over 15 breaths) at baseline left atrial pressure and at subthreshold and suprathreshold increases in left atrial pressure. At baseline, smoke significantly increased RAR activity from 12.1 +/- 4.2 to 16.2 +/- 4.2 impulses/breath (P < 0.05). At subthreshold increases in left atrial pressure (2.9 +/- 0.6 mmHg), smoke produced larger increases in RAR activity (12.3 +/- 3.3 to 22.5 +/- 4.1 impulses/breath; P < 0.05). Suprathreshold increases in left atrial pressure (9.2 +/- 1.1 mmHg) alone increased RAR activity from 10.9 +/- 3.2 to 19.8 +/- 5.9 impulses/breath (P < 0.05). Smoke had no additional effect (22.3 +/- 4.8 impulses/breath; P > 0.05). There was, however, a transient increase in RAR activity (1st 3 breaths of smoke) under all three conditions. Of nine SARs examined, only two were stimulated by smoke. We conclude that in the rabbit smoke-induced stimulation of RARs is augmented by mild pulmonary venous congestion. of RARs is augmented by mild pulmonary venous congestion.
Rapid neutrophil accumulation and protein oxidation in irradiated rat lungs
Authors: Fliss H. , Menard M.
Published: December 2017

Exposure of lungs to high doses of ionizing radiation can initiate an injurious acute inflammatory response. We show that neutrophil content in the lungs of rats exposed to 10 Gy whole body gamma radiation increased threefold 4.5 h after irradiation and returned to normal by 24 h. Oxidized methionine in the proteins of the lungs, heart, liver, kidney, and jejunum increased significantly in 2 h. Treatment with the antioxidant dithiothreitol immediately after irradiation prevented methionine oxidation. Methionine oxidation was also observed after intrabronchial instillation of phorbol myristate acetate, a model of neutrophil oxidant-mediated pulmonary injury, as well as in isolated lungs perfused with hypochlorous acid, confirming the ability of neutrophil oxidants to cause protein oxidation in lungs. No change in glutathione or protein sulfhydryl content was detected in irradiated lungs 4.5 h after irradiation, possibly as a result of protection by the observed increase in pulmonary glutathione reductase. We therefore show that the acute pulmonary inflammatory response to radiation involves rapid neutrophil accumulation, oxidant production, and protein oxidation.
Regional diaphragm shortening measured by sonomicrometry
Authors: Wakai Y. , Leevers A. M. , Road J. D.
Published: December 2017

Diaphragmatic shortening measured by sonomicrometry has been compared in the two major anatomic segments, costal and crural. Data obtained by videofluoroscopy found a variation in subsegmental shortening within segments (Sprung et al. J. Appl. Physiol. 67: 655–662, 1989). No reproducible pattern of subsegmental shortening has emerged, and the mechanisms leading to this subsegmental variation in shortening are unknown. Therefore, we compared subsegmental shortening in both segments of the diaphragm in seven supine pentobarbital-anesthetized dogs. Seven pairs of sonomicrometer transducers were implanted in the two segments, and subsegmental shortening during spontaneous breathing was measured. To determine potential mechanisms contributing to the variation in shortening, measurements were made during stimulated breathing, after epiphrenic stimulation, and during occluded breaths. We found electrical stimulation at physiological frequencies of 10 and 20 Hz reduced the variation in subsegmental shortening, whereas stimulated breathing did not. Occluded breaths showed a consistent decrease in the amount of shortening, particularly in the dome of the costal diaphragm, compared with shortening in the area of apposition. Comparison of shortening between segments revealed greater crural than costal shortening. We conclude that subsegmental variation in activation can contribute to variation in subsegmental shortening and that the afterload can effect shortening during occluded breaths.
Beta-adrenoceptor blockade and skeletal muscle energy metabolism during endurance exercise
Authors: van Baak M. A. , de Haan A. , Saris W. H. , van Kordelaar E. , Kuipers H. , van der Vusse G. J.
Published: December 2017

Twelve healthy male volunteers cycled to exhaustion at a workload corresponding to 70% of maximal aerobic power after administration of 80 mg of the beta 1+2-adrenoceptor antagonist propranolol and after administration of placebo by mouth. Exercise times until exhaustion were 39 +/- 7 and 86 +/- 7 min in the propranolol and placebo groups, respectively. Muscle inosine 5′-monophosphate content was significantly increased above resting levels at exhaustion after placebo. At exhaustion after propranolol, inosine 5′-monophosphate was not increased significantly and was lower than at exhaustion after placebo. No changes in ATP and the total adenine nucleotide content during exercise were found in the two tests. Muscle glycogen content was significantly reduced at exhaustion after placebo as well as after propranolol, but the levels were still significantly higher at exhaustion after propranolol than after placebo. No evidence for a shift in glycogen utilization among types I, IIa, and IIb fibers after propranolol was found. The results show that neither an imbalance between ATP utilization and ATP regeneration nor premature glycogen depletion, either in the whole muscle or in specific muscle fiber types, provides a satisfactory explanation for the premature fatigue during endurance exercise after propranolol.
Diuretic effect of acute hypoxia in humans: relationship to hypoxic ventilatory responsiveness and renal hormones
Authors: Swenson E. R. , Duncan T. B. , Goldberg S. V. , Ramirez G. , Ahmad S. , Schoene R. B.
Published: December 2017

Acute hypoxia causes increased sodium and water excretion. Animal studies suggest that this renal response is largely driven by direct peripheral arterial chemoreceptor stimulation, independent of accompanying changes in ventilation and acid-base status. Whether the diuresis and natriuresis observed in humans made acutely hypoxic are caused by peripheral chemoreceptor stimulation is not known, but, if so, we hypothesized that people with a high ventilatory response to hypoxia (high peripheral chemosensitivity) should have greater diuresis and natriuresis than those with a low ventilatory response to hypoxia. The isocapnic hypoxic ventilatory response (HVR) of 16 subjects on a fixed sodium intake was measured, as were their urinary volume and sodium and bicarbonate losses during 6 h of breathing air (in a normobaric environmental chamber) and, on the subsequent day, 12% O2. The isocapnic HVR correlated positively with hypoxic diuresis (r = 0.87) and natriuresis (r = 0.76). In contrast, the isocapnic HVR did not correlate with bicarbonate excretion, despite the expected respiratory alkalosis of acute hypoxia. The magnitude of diuresis and natriuresis with hypoxia did not correlate with changes in circulating aldosterone, renin, atrial natriuretic peptide, vasopressin, or a digoxin-like immunoreactive substance. These findings are compatible with a role of the peripheral arterial chemoreceptors in mediating the renal response to hypoxia in humans. The efferent pathway remains unknown.
Thyroid cartilage movements during breathing
Authors: Amis T. C. , Brancatisano A. , Tully A.
Published: December 2017

We measured lateral (outward) thyroid cartilage displacement (TCD) of the larynx in six supine anesthetized (intravenous chloralose) dogs. Combined left and right TCDs were measured with linear transducers attached by a thread to the thyroid alae. During tidal breathing via a tracheostomy, phasic inspiratory TCD occurred in all dogs [0.66 +/- 0.2 mm (mean +/- SE)] together with phasic inspiratory electromyographic activity in the cricothyroid (CT) and posterior cricoarytenoid (PCA) muscles. During brief tracheal occlusions, TCD increased significantly to 1.27 +/- 0.2 mm (P = 0.001), accompanied by an increase of 95–115% in the peak CT and PCA electromyograms. Bilateral supramaximal electrical stimulation of the external branches of the superior laryngeal nerve (ExSLN) produced a TCD of 9.9 +/- 0.8 mm; however, similar stimulation of the recurrent laryngeal nerve (RLN) produced a TCD of only 1.33 +/- 0.1 mm (P = 0.0001). Furthermore, bilateral section of the ExSLN in five dogs significantly reduced tidal TCD by 48.7 +/- 24.4% (P < 0.05), and bilateral section of both the ExSLN and RLN resulted in slight phasic inward TCD (-0.06 +/- 0.05 mm). Thus, it appears that the activities of both the CT and RLN-innervated muscles (probably the PCA muscle) contribute to tidal breathing TCD. These findings suggest that inspiratory dilation of the hypopharynx is mediated by contractions of CT and PCA muscles.
Intra-airway CO2 distribution during airway insufflation in ventilatory failure
Authors: Eckmann D. M. , Gavriely N.
Published: December 2017

Low-flow intratracheal gas insufflation is known to be an effective means of providing partial ventilatory support in respiratory failure. We studied the effects of catheter position on intraluminal CO2 concentration profiles and gas transport resistance during intra-airway insufflation at 0.15 l.kg-1.min-1 in six anesthetized paralyzed mechanically hypoventilated dogs. The two positions of the distal tip of the insufflation catheter were 0.5 cm proximal to and 4.0 cm distal to the carina. Local airway CO2 concentrations were measured via a sampling catheter passed through the tracheobronchial tree. Resistance to gas transport was calculated from the measured data. Arterial PO2 and arterial PCO2 remained constant with carinal and bronchial insufflation. Distal positioning of the insufflation tip resulted in a redistribution of ventilation between the lungs, with the ipsilateral lung being relatively hyperventilated and the contralateral lung being relatively hypoventilated. Intraluminal CO2 concentrations were markedly reduced in the ipsilateral lung compared with the profile in the contralateral lung during fresh gas delivery into the main-stem bronchus. The region of peak transport resistance was found to be in the second-generation airways during carinal insufflation and in the fourth-generation airways with intrabronchial insufflation. We conclude that gas exchange during low-flow insufflation occurs by the same mechanisms responsible for CO2 elimination in constant-flow ventilation. Overall gas exchange is not affected by position of the jet catheter.