bluuebunny/crossref_metadata_2025 huggingface dataset:
Oxygen transport to exercising leg in chronic hypoxia
Authors: Bender P. R. , Groves B. M. , McCullough R. E. , McCullough R. G. , Huang S. Y. , Hamilton A. J. , Wagner P. D. , Cymerman A. , Reeves J. T.
Published: December 2017

Residence at high altitude could be accompanied by adaptations that alter the mechanisms of O2 delivery to exercising muscle. Seven sea level resident males, aged 22 +/- 1 yr, performed moderate to near-maximal steady-state cycle exercise at sea level in normoxia [inspired PO2 (PIO2) 150 Torr] and acute hypobaric hypoxia (barometric pressure, 445 Torr; PIO2, 83 Torr), and after 18 days' residence on Pikes Peak (4,300 m) while breathing ambient air (PIO2, 86 Torr) and air similar to that at sea level (35% O2, PIO2, 144 Torr). In both hypoxia and normoxia, after acclimatization the femoral arterial-iliac venous O2 content difference, hemoglobin concentration, and arterial O2 content, were higher than before acclimatization, but the venous PO2 (PVO2) was unchanged. Thermodilution leg blood flow was lower but calculated arterial O2 delivery and leg VO2 similar in hypoxia after vs. before acclimatization. Mean arterial pressure (MAP) and total peripheral resistance in hypoxia were greater after, than before, acclimatization. We concluded that acclimatization did not increase O2 delivery but rather maintained delivery via increased arterial oxygenation and decreased leg blood flow. The maintenance of PVO2 and the higher MAP after acclimatization suggested matching of O2 delivery to tissue O2 demands, with vasoconstriction possibly contributing to the decreased flow.
Carbohydrate balance in competitive runners during successive days of intense training
Authors: Kirwan J. P. , Costill D. L. , Mitchell J. B. , Houmard J. A. , Flynn M. G. , Fink W. J. , Beltz J. D.
Published: December 2017

This study was designed to investigate the effect of intense training on muscle glycogen stores under conditions of controlled carbohydrate (CHO) intake. On two separate occasions, 10 highly trained distance runners increased their training load for 5 days (20 km/day, approximately 80% maximal O2 consumption) while eating a diet whose carbohydrate composition either equaled (EQ-CHO) or contained approximately 50% of the runner's estimated daily expenditure (LO-CHO). Total muscle glycogen levels were lower after the LO-CHO regimen. Photometric analysis of the glycogen content in individual fibers revealed that 27% type I and 17% type II fibers had optical densities less than 0.2 U after the LO-CHO regimen, whereas 7% type I and 0% type II were similarly depleted after the EQ-CHO diet. A linear relationship was observed between the histochemical and direct chemical analysis of muscle glycogen content. Treadmill O2 uptake measured at 185 and 238 m/min was higher during the LO-CHO than the EQ-CHO regimen. Ratings of perceived exertion were higher during the 238-m/min run for the LO-CHO regimen. After 3 days of rest, running economy and perception of effort returned to pretraining levels and muscle glycogen stores were approximately 85% of the pretraining values. Thus when CHO intake was only approximately 50% of the energy requirements there was a marked depletion of muscle glycogen stores, particularly in type I fibers, and a concomitant decrease in running economy and increased perception of fatigue.(ABSTRACT TRUNCATED AT 250 WORDS)
Cardiopulmonary resuscitation in the rat
Authors: von Planta I. , Weil M. H. , von Planta M. , Bisera J. , Bruno S. , Gazmuri R. J. , Rackow E. C.
Published: December 2017

A standardized method of cardiopulmonary resuscitation in rodents has been developed for anesthetized, mechanically ventilated rats. Ventricular fibrillation was induced and maintained by an alternating current delivered to the right ventricular endocardium. After 4 min of ventricular fibrillation, the chest was compressed with a pneumatic piston device. Eight of 14 animals were successfully resuscitated with DC countershock after 6 min of cardiac arrest. In confirmation of earlier studies from our laboratories in dogs, pigs, and human patients, this rodent model of cardiopulmonary resuscitation demonstrated large venoarterial [H+] and PCO2 gradients associated with reduced pulmonary excretion of CO2 during the low-flow state. Mean aortic pressure, coronary perfusion pressure, and end-tidal CO2 during chest compression were predictive of successful resuscitation.
Type II pneumocyte changes during hyperoxic lung injury and recovery
Authors: Holm B. A. , Matalon S. , Finkelstein J. N. , Notter R. H.
Published: December 2017

Adult rabbits exposed to 100% O2 for 64 h and then returned to room air for up to 200 h, develop a lung injury characterized by decreased levels of alveolar surfactant followed by a rebound recovery. In the present study we isolated alveolar type II cells from rabbits at various times during hyperoxic exposure and recovery and measured rates of phosphatidylcholine (PC) synthesis, cellular lipid content, and the specific activity of glycerol 3-phosphate (G-3-P) acyltransferase, an enzyme that catalyzes one of the early reactions in phosphoglyceride biosynthesis. These biochemical parameters were compared with measurements of cell size and cell cycle phase by laser flow cytometry. Results showed that alterations in alveolar phospholipid levels in vivo correlated consistently with cellular lipid metabolic changes measured in isolated type II pneumocytes. In particular, alveolar pneumocytes isolated from lungs of rabbits exposed to 100% O2 for 64 h exhibited a 60% decrease in PC synthesis, cell lipid content, and G-3-P acyltransferase activity. All variables then followed a pattern of recovery to normal and ultimately supranormal levels beginning at approximately 3 days postexposure, at which point there was also a measured increase in the number of type II cells in S phase. These findings suggest that O2-induced changes in type II cell surfactant biosynthesis may account, at least in part, for observed changes in lung phospholipid levels in vivo.
Effect of aortic arterial catheterization on tissue glycogen content
Authors: Moore R. L. , Hilty M. R. , Musch T. I.
Published: December 2017

Measurements of hemodynamics and blood metabolites in rats are often made by insertion of a small polyethylene (PE-50) catheter into the aorta via the carotid artery. Although the effect of this type of procedure on animal body weight has been described, little information exists regarding the quantitative and temporal effects of this procedure on liver and skeletal muscle glycogen concentration. Relative to the control group (group C), liver glycogen concentration was reduced by 56% 24 h after catheterization (group CN). With respect to liver glycogen concentration, it was apparent that a postcatheterization recovery period of variable duration (2-8 days; group CNR) based on attainment of a normal food consumption-to-body weight ratio (FdWt/BdWt) was more effective than was a fixed 6-day recovery period (group CN6). This was probably due to the large between-animal variability in recovery times required to reach normal FdWt/BdWt values. After aortic catheterization, FdWt/BdWt was a reasonable predictor of postprocedural liver (y = 2,601x + 43.9; r = 0.72; P less than 0.01) and diaphragm muscle glycogen concentration (y = 146.3x + 14.0; r = 0.57; P less than 0.05). Aortic catheterization did not affect the glycogen concentration in the other skeletal muscles examined. Since the results of certain types of experiments can be significantly influenced by liver glycogen concentration, the use of FdWt/BdWt on 24-h food intake as a general indicator of recovery after instrumentation via aortic catheterization is proposed.
Hemodynamic effects of arginine vasopressin in rats adapted to chronic hypoxia
Authors: Jin H. K. , Yang R. H. , Chen Y. F. , Thornton R. M. , Jackson R. M. , Oparil S.
Published: December 2017

Acute and chronic pulmonary and systemic hemodynamic responses to arginine vasopressin (AVP) were examined in 4-wk hypoxia-adapted and air control rats. AVP, administered intravenously as bolus injections or sustained infusions, produced major dose-dependent V1-receptor-mediated reductions in mean pulmonary arterial pressure in hypoxia-adapted rats. These effects were comparable in pentobarbital-anesthetized, thoracotomized animals and in conscious, intact rats. Chronic infusions of AVP induced a sustained reduction in mean pulmonary arterial pressure and partially prevented the development of pulmonary hypertension without changing systemic arterial pressure. AVP induced significant decreases in cardiac output in both groups; the cardiac output response was not significantly different in hypoxia-adapted and air control animals. AVP induced almost no change in MPAP in air control rats. Furthermore the systemic pressor effects of AVP were significantly blunted in hypoxia-adapted rats compared with air controls. We conclude that the pulmonary depressor and blunted systemic pressor effects of AVP observed in hypoxia-adapted rats may be related to release of a vasodilator, such as endothelium-derived relaxing factor, vasodilator prostaglandins, or atrial natriuretic peptides. Further study is needed to elucidate these mechanisms and assess the usefulness of AVP and/or its analogues in the treatment and prevention of hypoxia-induced pulmonary hypertension.
Expiratory neural activities in gasping
Authors: St John W. M. , Zhou D. , Fregosi R. F.
Published: December 2017

The purpose was to characterize expiratory-related neural activities in eupnea and gasping. In decerebrate and vagotomized cats, activities were recorded from the phrenic nerve, spinal intercostal and abdominal nerves, and recurrent laryngeal nerve and its branches. Neural inspiration was defined by phrenic discharge. The spinal and laryngeal nerves discharged in inspiration, expiration, or during both phases. Gasping was induced by freezing the brain stem at the pontomedullary junction, exposure to asphyxia or anoxia, or ligation of the basilar artery and its branches. In gasping, peak phrenic activity typically increased as did inspiratory-related activities of laryngeal and spinal nerves. Expiratory activities were greatly reduced in gasping, with some activities being completely eliminated. Reductions of expiratory activity were more prominent for spinal than laryngeal nerves. Similar results were obtained in cats having intact vagi that were ventilated with a servo-respirator so that lung inflation paralleled phrenic activity. The concept that gasping differs fundamentally form other ventilatory patterns is discussed.
Transmission to the chest of sound introduced at the mouth
Authors: Kraman S. S. , Bohadana A. B.
Published: December 2017

We examined the transmission to the chest wall of white noise and 25-Hz square-wave-generated noise introduced at the mouth of five healthy subjects. The output audio signals were recorded over the left and right upper and lower lung zones, posteriorly. Sound measurements were made during apnea at functional residual capacity, total lung capacity, and residual volume both after breathing air and an 80% He-20% O2 (heliox) gas mixture. We calculated the peak-to-peak amplitude, the peak frequency, and the midpower frequency of the output sound. We found no consistent variations in the values of these indexes due to lung volume or resident gas density. In all cases, the transmitted sound was most intense at the right upper zone. This could not be explained on the basis of technical factors but was probably the result of normal asymmetry of the mediastinal anatomy. These data suggest that sound introduced through the mouth of healthy individuals excites intrathoracic structures but is transmitted through the parenchyma in such a manner that it is not markedly affected by familiar physiological variables. This must be taken into account if objective acoustical tests of lung physiology are to be developed.
Effect of liver glycogen content on glucose production in running rats
Authors: Vissing J. , Wallace J. L. , Galbo H.
Published: December 2017

The influence of supranormal compared with normal hepatic glycogen levels on hepatic glucose production (Ra) during exercise was investigated in chronically catheterized rats. Supranormal hepatic glycogen levels were obtained by a 24-h fast-24-h refeeding regimen. During treadmill running for 35 min at a speed of 21 m/min, Ra and plasma glucose increased more (P less than 0.05) and liver glucogen breakdown was larger in fasted-refed compared with control rats, although the stimuli for Ra were higher in control rats, the plasma concentrations of insulin and glucose being lower (P less than 0.05) in control compared with fasted-refed rats. Also, plasma concentrations of glucagon and both catecholamines tended to be higher and muscle glycogenolysis lower in control compared with fasted-refed rats. Lipid metabolism was similar in the two groups. The results indicate that hepatic glycogenolysis during exercise is directly related to hepatic glycogen content. The smaller endocrine glycogenolytic signal in face of higher plasma glucose concentrations in fasted-refed compared with control rats is indicative of metabolic feedback control of glucose mobilization during exercise. However, the higher exercise-induced increase in Ra, plasma glucose, and liver glycogen breakdown in fasted-refed compared with control rats indicates that metabolic feedback mechanisms are not able to accurately match Ra to the metabolic needs of working muscles.
Surfactant subtypes in mice: characterization and quantitation
Authors: Gross N. J. , Narine K. R.
Published: December 2017

Surfactant obtained by bronchoalveolar lavage of normal adult mice was separated into subtypes by a one-step centrifugation to equilibrium on continuous sucrose gradients. Mouse surfactant resolved in this way exists in three subtypes with similar phospholipid compositions. A "light" subtype of buoyant density 1.027 +/- 0.012 (SD) g/ml comprises 43 +/- 18% of the total alveolar lavage phospholipid, has little surface activity, and consists exclusively of small unilamellar vesicles. A "heavy" subtype of buoyant density 1.055 +/- 0.016 g/ml comprises 48 +/- 11% of the total, is surface active, and consists of small amounts of tubular myelin among large empty vesicles. A third component, called "ultraheavy," comprises 9 +/- 4% of the total alveolar lavage phospholipid, has a density of 1.072 +/- 0.020 g/ml, is surface active, and consists of large aggregates of tubular myelin associated with lamellar bodylike structures. Labeling studies suggested that the ultraheavy material was labeled first and was of the same density as purified lamellar bodies. These results are consistent with the view that, in mice, surfactant is secreted into the alveolar compartment in an ultraheavy form, which evolves into the heavy and light forms.
Chest wall impedance partitioned into rib cage and diaphragm-abdominal pathways
Authors: Barnas G. M. , Yoshino K. , Stamenovic D. , Kikuchi Y. , Loring S. H. , Mead J.
Published: December 2017

We measured chest wall "pathway impedances" (ratios of pressure changes to rates of volume displacement at the surface) with esophageal and gastric balloons and inductance plethysmographic belts around the rib cage and abdomen during forced volume oscillations (5% vital capacity, 0.5–4 Hz) at the mouth of five relaxed, seated subjects. Volume displacements of the total chest wall surface, measured by summing the rib cage and abdominal signals, approximated measurements using volume-displacement, body plethysmography over the entire frequency range. Resistance (R) and elastance (E) of the diaphragm-abdomen pathway were several times greater than those of the rib cage pathway, except at the highest frequencies where diaphragm-abdominal E was small. R and E of the diaphragm-abdomen pathway and of the rib cage pathway showed the same frequency dependencies as that of the total chest wall: R decreased markedly as frequency increased, and E (especially in the diaphragm-abdomen) decreased at the highest frequencies. These results suggest that the chest wall can be reasonably modeled, over the frequency range studied, as a system with two major pathways for displacement. Each pathway seems to exhibit behavior that reflects nonlinear, rate-independent dissipation as well as viscoelastic properties. Impedances of these pathways are useful indexes of changes in chest wall mechanical behavior in different situations.
Effect of various doses of cocaine on endurance capacity in rats
Authors: Bracken M. E. , Bracken D. R. , Winder W. W. , Conlee R. K.
Published: December 2017

To determine the effects of a variety of doses of cocaine on endurance capacity, rats were injected intraperitoneally with either 0.1, 0.5, 2.5, 12.5, or 20 mg/kg body wt 20 min before running to exhaustion at 26 m/min up a 10% grade. Animals given saline ran 116 +/- 9 (SE) min. At doses of 12.5 and 20 mg/kg, cocaine reduced endurance time significantly (34 and 74%, respectively). At rest the drug had no effect on liver or fast-twitch muscle glycogen but significantly reduced (20–40%) soleus glycogen at the two highest doses. However, at exhaustion, the quantity of glycogen depleted in the fast-twitch red and white vastus muscles was similar in all groups despite the reduced run times of the animals receiving a higher dose implying a greater rate of glycogenolysis due to cocaine. Blood lactate in the 20 mg/kg group (9.9 +/- 1.2 mM) at exhaustion was nearly twice that of the saline controls at exhaustion (5.1 +/- 0.6). Before exercise plasma norepinephrine (at doses of 2.5, 12.5 and 20 mg/kg) was higher than saline controls and remained higher (20 mg/kg groups) at exhaustion. We conclude that high doses of cocaine cause rapid muscle glycogen depletion and early fatigue. The mechanism by which cocaine causes these effects is not clear.
Differential responses of expiratory muscles to chemical stimuli in awake dogs
Authors: Smith C. A. , Ainsworth D. M. , Henderson K. S. , Dempsey J. A.
Published: December 2017

We assessed respiratory muscle response patterns to chemoreceptor stimuli (hypercapnia, hypoxia, normocapnic hypoxia, almitrine, and almitrine + CO2) in six awake dogs. Mean electromyogram (EMG) activities were measured in the crural (CR) diaphragm, triangularis sterni (TS), and transversus abdominis (TA). Hypercapnia and normocapnic hypoxia caused mild to marked hyperpnea [2–5 times control inspiratory flow (VI)] and increased activity in CR diaphragm, TS, and TA. When hypocapnia was permitted to develop during hypoxia and almitrine-induced moderate hyperpnea, CR diaphragm activity increased, whereas TS and TA activities usually did not change or were reduced below control. Over time in hypercapnia, CR diaphragm, TS, and TA were augmented and maintained at these levels over many minutes; with hypoxic hyperventilation CR diaphragm, TS, and TA were first augmented but then CR diaphragm remained augmented while TS and, less consistently, TA were inhibited over time. Marked hyperpnea (4–5 times control) due to carotid body stimulation increased TA and TS EMG activity despite an accompanying hypocapnia. We conclude that in the intact awake dog 1) carotid body stimulation augments the activity of both inspiratory and expiratory muscles; 2) hypocapnia overrides the augmenting effect of carotid body stimulation on expiratory muscles during moderate hyperpnea, usually resulting in either no change or inhibition; 3) at higher levels of hyperpnea both chemoreceptor stimulation and stimulatory effects secondary to a high ventilatory output favor expiratory muscle activation; these effects override any inhibitory effects of a coincident hypocapnia; and 4) expiratory muscles of the rib cage/abdomen may be augmented/inhibited independently of one another.
Effect of testosterone on muscle mass and muscle protein synthesis
Authors: Griggs R. C. , Kingston W. , Jozefowicz R. F. , Herr B. E. , Forbes G. , Halliday D.
Published: December 2017

We have studied the effect of a pharmacological dose of testosterone enanthate (3 mg.kg-1.wk-1 for 12 wk) on muscle mass and total-body potassium and on whole-body and muscle protein synthesis in normal male subjects. Muscle mass estimated by creatinine excretion increased in all nine subjects (20% mean increase, P less than 0.02); total body potassium mass estimated by 40K counting increased in all subjects (12% mean increase, P less than 0.0001). In four subjects, a primed continuous infusion protocol with L-[1–13C]leucine was used to determine whole-body leucine flux and oxidation. Whole-body protein synthesis was estimated from nonoxidative flux. Muscle protein synthesis rate was determined by measuring [13C]leucine incorporation into muscle samples obtained by needle biopsy. Testosterone increased muscle protein synthesis in all subjects (27% mean increase, P less than 0.05). Leucine oxidation decreased slightly (17% mean decrease, P less than 0.01), but whole-body protein synthesis did not change significantly. Muscle morphometry showed no significant increase in muscle fiber diameter. These studies suggest that testosterone increases muscle mass by increasing muscle protein synthesis.
Mouth pressure curve on abrupt interruption of airflow during forced expiration
Authors: Ohya N. , Huang J. , Fukunaga T. , Toga H.
Published: December 2017

An attempt was made to investigate how the mouth pressure curve represents the process of air flowing into the collapsed segment downstream to the choke point when the airflow is abruptly interrupted at the mouth during forced expiration. Immediately after the interruption of airflow, the mouth pressure suddenly increased (phase 1), followed by a slower rise in pressure (phase 2) within approximately 100 ms until the pressure reached the alveolar pressure. The pleural and alveolar pressures remained constant during this process. The first phase of the abrupt rise represented the pressure induced by the instantaneous interruption of the airflow itself. Analysis of the supramaximal flow (Vsupramax) observed after resumption of the airflow suggested that the choke point remained constant during the second phase of the mouth pressure after interruption of maximal flow (Vmax). From these results, examination of the second phase of the mouth pressure curve may provide useful information about the downstream segment of the airway.
Motor unit territories supplied by primary branches of the phrenic nerve
Authors: Hammond C. G. , Gordon D. C. , Fisher J. T. , Richmond F. J.
Published: December 2017

Recent studies have demonstrated that, under certain circumstances, the diaphragm does not contract as a homogeneous unit. These observations suggest that motor units may not be randomly distributed throughout the muscle but confined to localized subvolumes. In the present study, electromyographic (EMG) and glycogen depletion methods were combined to investigate the organization of motor units supplied by the primary branches of the phrenic nerve in the cat. Four primary branches are generally present, one branch to the crus and three branches to the sternocostal region. The gross motor-unit territory of each of the four phrenic primary branches was determined by stimulating each nerve separately, while recording from nine EMG electrodes distributed over the hemidiaphragm. Stimulation of the crural branch evoked activity in the ipsilateral crus, whereas stimulation of each of the remaining branches evoked activity in discrete but overlapping areas of the sternocostal diaphragm. A more precise analysis of the distribution and borders of the motor territories was obtained by mapping regions depleted of muscle glycogen due to stimulation of each primary branch for 90 min. Glycogen depletion results closely matched the EMG findings of a localized distribution of motor units served by single primary branches. Stimulation of the crural branch typically caused depletion of the ipsilateral crus, whereas the sternocostal branches each served a striplike compartment. In the majority of cases, the borders of the sternocostal compartments were relatively abrupt and consisted of a 1- to 2-mm transition zone of depleted and nondepleted fibers. These studies demonstrate that motor unit territories of the primary branches of the phrenic nerve are highly delineated. This compartmentalization provides the central nervous system with the potential for a more precise regional motor control of costal and crural diaphragm than previously suspected.
Force deficit of vascularized skeletal muscle grafts in rabbits
Authors: Burton H. W. , Stevenson T. R. , White T. P. , Hartman J. , Faulkner J. A.
Published: December 2017

Through autografting experiments on 9-g rectus femoris (RFM) muscles in rabbits, we substantiated a previous observation that the maximum isometric tetanic force (Po) and specific Po (N/cm2) of neurovascular-intact grafts are not different from grafts made with neurovascular repair. We then tested the hypotheses that the specific Po of vascularized grafts is significantly less than that of control RFM muscles and the deficit in the specific Po is associated with increases in connective tissue and interstitial space. The specific Po of the grafts was 65% of the value for control RFM muscles. Connective tissue protein concentration of grafts was 3.8 times greater than the control value of 16.6 +/- 3 micrograms/mg wet mass, but this only accounted for a 5% correction in specific Po. The volume of interstitial space did not differ between grafts and control muscles. We conclude that the deficit of 35% in specific Po of vascularized grafts compared with control values is partially explained by an increase in connective tissue, but a 30% unresolved deficit remains.
Development of hypertension in rats during chronic exposure to cold
Authors: Fregly M. J. , Kikta D. C. , Threatte R. M. , Torres J. L. , Barney C. C.
Published: December 2017

Resting systolic, diastolic, and mean blood pressures (MBP), as well as heart rates, of unanesthetized, unrestrained, cold-acclimated (CA, 4 wk, 6 degrees C) rats were measured by direct arterial cannula and compared with those of controls maintained at 25 degrees C. Exposure to cold increased all these measurements significantly. Mean heart weight of CA rats was also increased significantly above that of controls. The responsiveness of MBP and heart rate to administration of the beta-adrenergic agonist, isoproterenol (3, 5, and 8 micrograms/kg ip), to unanesthetized, unrestrained, CA rats during exposure to air at 6 degrees C was similar to, and possibly less than, that of warm-acclimated (WA) rats measured at 25 degrees C. Acute administration of the alpha-adrenergic agonist, phenylephrine (100 micrograms/kg ip), to CA rats while in air at 6 degrees C induced less of a change in MBP from pretreatment level than was observed in WA rats. However, no differences were observed between groups when changes in heart rate from pretreatment level were compared. A similar statement may be made for a higher dose of phenylephrine (150 micrograms/kg ip), although MBP were elevated to higher levels in both groups with the higher dose. Abrupt exposure of WA rats to cold (6 degrees C) resulted in a sharp increase in heart rate and a more gradual increase in MBP over a period of 1 h. Removal of CA rats from 6 to 25 degrees C resulted in a gradual decrease in heart rate with no significant change in MBP during the ensuing hour.(ABSTRACT TRUNCATED AT 250 WORDS)
Preferential fatigue of the rib cage muscles during inspiratory resistive loaded ventilation
Authors: Hershenson M. B. , Kikuchi Y. , Tzelepis G. E. , McCool F. D.
Published: December 2017

Because the inspiratory rib cage muscles are recruited during inspiratory resistive loaded breathing, we hypothesized that such loading would preferentially fatigue the rib cage muscles. We measured the pressure developed by the inspiratory rib cage muscles during maximal static inspiratory maneuvers (Pinsp) and the pressure developed by the diaphragm during maximal static open-glottis expulsive maneuvers (Pdimax) in four human subjects, both before and after fatigue induced by an inspiratory resistive loaded breathing task. Tasks consisted of maintaining a target esophageal pressure, breathing frequency, and duty cycle for 3–5 min, after which the subjects maintained the highest esophageal pressure possible for an additional 5 min. After loading, Pinsp decreased in all subjects [control, -128 +/- 14 (SD) cmH2O; with fatigue, -102 +/- 18 cmH2O; P less than 0.001, paired t test]. Pdimax was unchanged (control, -192 +/- 23 cmH2O; fatigue, -195 +/- 27 cmH2O). These data suggest that 1) inability to sustain the target during loading resulted from fatigue of the inspiratory rib cage muscles, not diaphragm, and 2) simultaneous measurement of Pinsp and Pdimax may be useful in partitioning muscle fatigue into rib cage and diaphragmatic components.
Effect of epithelium on mucus secretion from feline tracheal submucosal glands
Authors: Sasaki T. , Shimura S. , Sasaki H. , Takishima T.
Published: December 2017

We studied the effect of airway epithelium on mucus secretion by use of an isolated tracheal submucosal gland preparation reported previously (J. Appl. Physiol. 60: 1237–1247, 1986). Mucus glycoconjugate release from submucosal glands of feline trachea was examined using [3H]glucosamine as a mucus precursor. Isolated glands showed significantly higher secretory responses to cholinergic, alpha-, and beta-adrenergic agonists and dibutyryladenosine 3′,5′-cyclic monophosphate (average 400% of control) than the conventional tracheal mucosal explants, which contained epithelium and submucosal tissues in addition to submucosal glands (average 160% of control). The addition of isolated epithelium depressed the secretory response of isolated glands to the same level as that of tracheal explants. However, the supernatant from isolated epithelium failed to inhibit secretory responses to methacholine in isolated glands, suggesting that the epithelium-derived inhibitory factor to secretion may be short-lived. Leukotriene D4 antagonist (FPL 55712), cyclooxygenase and/or lipoxygenase inhibitors (indomethacin or BW 755C) caused no significant change in the inhibitory action of epithelium, suggesting that the inhibition is not due to arachidonic acid metabolites. The newly found secretory inhibitory action of epithelium is of particular interest in the pathogenesis of hypersecretion associated with epithelial damage.
P1 and P2 purinergic receptor signal transduction in rat type II pneumocytes
Authors: Warburton D. , Buckley S. , Cosico L.
Published: December 2017

Extracellular ATP is a potent agonist of surfactant phosphatidylcholine (PC) exocytosis from type II pneumocytes in culture. We studied P1 and P2 receptor signal transduction in type II pneumocytes. The EC50 for ATP on PC exocytosis was 10(-6) M, whereas the EC50 for ADP, AMP, adenosine, and the nonmetabolizable ATP analogue alpha,beta-methylene ATP was 10(-4) M. The rank order of agonists for PC exocytosis was ATP greater than ADP greater than AMP greater than adenosine greater than alpha,beta-methylene ATP. The rank order of agonists for phosphatidylinositol (PI) hydrolysis was ATP greater than ADP, whereas AMP, adenosine, and alpha,beta-methylene ATP did not stimulate PI hydrolysis. ATP (10(-4) M) caused a 15-fold increase in adenosine 3′,5′-cyclic monophosphate (cAMP) production, and the nonmetabolizable adenosine analogue 5′-N-ethylcarboxyamidoadenosine (10(-6) M) increased cAMP production threefold. The effects of both these agonists on cAMP production were completely inhibited by the adenosine antagonist 8-phenyltheophylline (10(-5) M). The effects of ATP (10(-4) M) on PC exocytosis were inhibited 38% by 10(-5) M 8-phenyltheophylline. Thus, ATP regulates PC exocytosis by activating P2 receptors, which stimulate PI hydrolysis to inositol phosphate, as well as by activating P1 receptors, which stimulate cAMP production. Interactions between the P1 and P2 pathways may explain the high potency of extracellular ATP as an agonist of PC exocytosis.
Role of venoconstriction in thromboxane-induced pulmonary hypertension and edema in lambs
Authors: Yoshimura K. , Tod M. L. , Pier K. G. , Rubin L. J.
Published: December 2017

We evaluated the dose response to a stable thromboxane (Tx) A2 analogue (sTxA2; 0.3–30 micrograms) in the pulmonary circulation and its effect on the distribution of pressure gradients determined by the occlusion technique in isolated nonblood perfused newborn lamb lungs. The total pulmonary pressure gradient (delta Pt) was partitioned into pressure drops across the relatively indistensible arteries and veins (delta Pv) and relatively compliant vessels. We also evaluated the effects of prostacyclin (PGI2) and a Tx receptor antagonist (ONO 3708) on the sTxA2-induced pulmonary responses. Injection of sTxA2 caused a dose-related increase in the pulmonary arterial pressure, with the primary component of the increase in delta Pt (4.1 +/- 0.8 to 13.9 +/- 0.4 Torr) at 30 micrograms derived from the prominent rise in delta Pv (1.8 +/- 0.3 to 9.8 +/- 0.9 Torr). Infusion of PGI2 (0.4 microgram.kg-1.min-1) reduced the response to sTxA2 mainly by attenuating the delta Pv elevation. Infusion of ONO 3708 (100 micrograms.kg-1.min-1) completely abolished the sTxA2-induced pulmonary hypertension. Injection of sTxA2 resulted in pulmonary edema characterized by a significant increase in wet-to-dry lung weight ratio (9.13 +/- 0.35 vs. 7.15 +/- 0.41 in control lungs). The sTxA2-induced pulmonary edema was increased by PGI2 and inhibited by ONO 3708. We conclude that thromboxane-induced pulmonary hypertension is primarily produced by venoconstriction and prostacyclin may worsen the edema induced by thromboxane.
Relationship between respiratory muscle function and age, sex, and other factors
Authors: Chen H. I. , Kuo C. S.
Published: December 2017

To investigate the effects of gender and age on respiratory muscle function, 160 healthy volunteers (80 males, 80 females) were divided into four age groups. Twenty-eight of the male subjects were smokers. After the subjects were familiarized with the experimental procedure, respiratory muscle strength, inspiratory muscle endurance, and spirometric function, including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC, tidal volume, breathing rate, and duty cycle, were measured. The respiratory muscle strength was indicated by the maximal static inspiratory and expiratory pressures (PImmax and PEmmax). Inspiratory muscle endurance was determined by the time the subject was able to sustain breathing against an inspiratory pressure load on a modified Nickerson-Keens device. The results showed that 1) except for inspiratory muscle endurance and FEV1/FVC, men had greater respiratory muscle and pulmonary functions than women, 2) respiratory muscle function and pulmonary function decreased with age, 3) smoking tended to lower duty cycle and FEV1/FVC and to enhance PE,mmax, and 4) inspiratory muscle endurance was greater in men who were physically active than in those who were sedentary. Therefore we conclude that there are sexual and age differences in respiratory muscle strength and pulmonary function and that smoking or physical activity may affect respiratory muscle function.
Effect of cAMP on ciliary function in rabbit tracheal epithelial cells
Authors: Tamaoki J. , Kondo M. , Takizawa T.
Published: December 2017

To study the effect of adenosine 3′,5′-cyclic monophosphate (cAMP) on respiratory ciliary activity, we measured ciliary beat frequency (CBF) of rabbit tracheal epithelium by a photoelectric method in response to cAMP analogues and agents that can increase endogenous cAMP production. Addition of 8-bromo-cAMP dose dependently enhanced CBF, with the maximal increase and the concentration necessary to produce a half-maximal response (KD) being 31.0 +/- 3.4% (SE) (P less than 0.001) and 3.2 +/- 1.5 x 10(-7) M, respectively. Other structurally dissimilar cAMP analogues dibutyryl cAMP and chlorophenylthio-cAMP likewise caused increases in CBF. The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine and the adenylate cyclase stimulator forskolin also augmented CBF in a dose-dependent fashion and were accompanied by the increases in intracellular concentrations of cAMP. Ciliary discoordination was not observed in any of the experiments. These results suggest that cAMP may accelerate mucociliary clearance through the activation of ciliary motility and that intracellular cAMP levels appear to be an important determinant for the lung mucociliary transport functions.
Pulmonary gas exchange in panting dogs
Authors: Meyer M. , Hahn G. , Buess C. , Mesch U. , Piiper J.
Published: December 2017

Pulmonary gas exchange during panting was studied in seven conscious dogs (32 kg mean body wt) provided with a chronic tracheostomy and an exteriorized carotid artery loop. The animals were acutely exposed to moderately elevated ambient temperature (27.5 degrees C, 65% relative humidity) for 2 h. O2 and CO2 in the tracheostomy tube were continuously monitored by mass spectrometry using a special sample-hold phase-locked sampling technique. PO2 and PCO2 were determined in blood samples obtained from the carotid artery. During the exposure to heat, central body temperature remained unchanged (38.6 +/- 0.6 degrees C) while all animals rapidly switched to steady shallow panting at frequencies close to the resonant frequency of the respiratory system. During panting, the following values were measured (means +/- SD): breathing frequency, 313 +/- 19 breaths/min; tidal volume, 167 +/- 21 ml; total ventilation, 52 +/- 9 l/min; effective alveolar ventilation, 5.5 +/- 1.3 l/min; PaO2, 106.2 +/- 5.9 Torr; PaCO2, 27.2 +/- 3.9 Torr; end-tidal-arterial PO2 difference [(PE′ - Pa)O2], 26.0 +/- 5.3 Torr; and arterial-end-tidal PCO2 difference, [(Pa - PE′)CO2], 14.9 +/- 2.5 Torr. On the basis of the classical ideal alveolar air approach, parallel dead-space ventilation accounted for 54% of alveolar ventilation and 66% of the (PE′ - Pa)O2 difference. But the steepness of the CO2 and O2 expirogram plotted against expired volume suggested a contribution of series in homogeneity due to incomplete gas mixing.
Source of ethane in expirate of rats ventilated with 100% oxygen
Authors: Habib M. P. , Katz M. A.
Published: December 2017

Ethane in alveolar expirate may have its source in organs other than the lung and be transported to the lung for elimination. We determined ethane production rates in rats (group I) ventilated with hydrocarbon-free air (HFA) before and after exsanguination. To determine whether the lung is the source of increased ethane production during exposure to 100% O2, we measured ethane in the expirate of nine exsanguinated, Sprague-Dawley rats (group II) mechanically ventilated with HFA and then with 100% O2. In all nine animals, ethane elimination rates on 100% O2 increased compared with HFA values. In five of the nine rats, HFA ventilation was reinstated after O2 (group III). In all five, ethane elimination fell with HFA ventilation compared with the value on 100%. Six rats with circulation intact were ventilated with HFA and then 100% O2 (group IV). Ethane production rate for group IV animals breathing HFA was not significantly different from the exsanguinated animals in group II while ventilated with HFA. The mean increase in ethane production for the group II animals was not significantly different from the group IV animals. Lung slices from four other rats (group V) were incubated in saline at 37 degrees C with FeCl2 (10 mg) added to enhance free radical formation. Paired lung samples from the same rat were incubated with either HFA or 100% O2. Headspace gas was analyzed chromatographically for ethane at 120 min. Mean ethane in the O2 samples was higher than for HFA. Rat lung tissue is the main source of increased ethane production during 100% O2 exposure.
Verapamil: a novel probe of surfactant secretion from rat type II pneumocytes
Authors: Warburton D. , Parton L. , Buckley S. , Cosico L.
Published: December 2017

Surfactant from type II pneumocytes prevents the alveolar atelectasis found in both the neonatal and adult forms of respiratory distress syndrome. We have found that verapamil, a phenylalkene with calcium channel and alpha 1-receptor binding properties, has a multiphasic concentration effect on surfactant secretion from [3H]choline-labeled rat type II pneumocytes in culture. Verapamil (10(-8) M) caused a 24% stimulation of surfactant secretion, whereas an 8% inhibition was found at 10(-6) M and a 70% stimulation was found at 10(-4) M. Lactate dehydrogenase release occurred at 5 x 10(-4) M verapamil. Verapamil (10(-4) M) also produced a 100% increase in adenosine 3′5′-cyclic monophosphate (cAMP) in comparison with concentrations of less than or equal to 10(-6) M, an effect that could not be blocked by propranolol (10(-4) M). Verapamil (10(-6) M) increased the total formation of inositol phosphates (IP) by 23% in comparison with IP formation in control cells. Calcium influx was inhibited 15% by 10(-8) M verapamil and 37% by 10(-4) M verapamil. Calcium efflux was stimulated 44% by 10(-5) M verapamil. In combination with 50% effective concentrations (EC50) of terbutaline, phorbol ester, and ATP, the respective effects of verapamil (10(-4) M) on surfactant secretion were approximately additive. We conclude that verapamil has a novel multiphasic concentration effect on surfactant secretion, which appears to involve several signal transduction pathways including cAMP formation, IP formation, inhibition of calcium influx, and stimulation of calcium efflux.
Effects of reactive oxygen species on prostacyclin production in perinatal rat lung cells
Authors: Lee D. S. , McCallum E. A. , Olson D. M.
Published: December 2017

A differentiation-arrested primary cell culture model was used to examine the role of reactive oxygen species in the control of prostacyclin (PGI2) production in the perinatal rat lung. Coincubation of the lung cells with arachidonic acid (AA) and xanthine (X, 0.25 mM) plus xanthine oxidase (XO, 10 mU/ml) or with AA and glucose (25 mM) plus glucose oxidase (25 mU/ml) augmented the AA-induced PGI2 output. Superoxide dismutase (10 U/ml) did not alter the X + XO effect, whereas catalase (10 U/ml) eliminated both X + XO and glucose plus glucose oxidase effects. H2O2 (1–200 microM) showed a dose-related biphasic augmentation with peak stimulation at 20 microM. Catalase again blocked this effect, but dimethylthiourea, a hydroxyl radical scavenger, did not. A 20-min pretreatment of the cells with X + XO, glucose plus glucose oxidase, or H2O2, however, diminished the capacity of the cells to convert exogenous AA to PGI2. This pretreatment effect was also blocked by catalase. The responses were similar in lung cells obtained from day 20 rat fetuses (term = 22 days) and 1-day-old newborn rats. Lactate dehydrogenase release was not detected during treatment periods but increased significantly after exposure to reactive oxygen species.(ABSTRACT TRUNCATED AT 250 WORDS)
Circulatory responses to heat after celiac ganglionectomy or adrenal demedullation
Authors: Kregel K. C. , Gisolfi C. V.
Published: December 2017

Chloraloseanesthetized rats were implanted with Doppler flow probes on the mesenteric, renal, and external caudal arteries and were exposed to an ambient temperature of 40 degrees C. Heart rate, core (Tc) and tail-skin temperatures, and mean arterial blood pressure (MAP) were also monitored. Before heating, the celiac ganglion was removed (ganglionectomy) from one group of animals (n = 11) and a bilateral adrenal demedullation was performed in a second group (n = 14). As Tc progressively increased from 37 degrees C to 43 degrees C, MAP rose to a plateau then fell precipitously as Tc exceeded 41 degrees C. Ganglionectomy eliminated the rise in mesenteric resistance (P less than 0.05) and attenuated the rise in MAP compared with an intact control group (n = 11). Ganglionectomy also increased the heating rate (P less than 0.05) and reduced heat tolerance time (P less than 0.05). Demedullation attenuated the rise in both mesenteric resistance and MAP (P less than 0.05) and increased the rate of heating (P less than 0.05) compared with controls (n = 10). Renal and caudal resistance changes were similar in all groups. These data show the importance of intact adrenal medullas and sympathetic innervation to the splanchnic region in contributing to thermal tolerance in the rat. However, neither factor alone can explain splanchnic vasoconstriction during severe heat stress.
Substance P-induced effects in guinea pig lungs: effects of thiorphan and captopril
Authors: Drazen J. M. , Shore S. A. , Gerard N. P.
Published: December 2017

The effects of the neutral metalloendopeptidase inhibitor, thiorphan, and the angiotensin-converting enzyme inhibitor, captopril, on the changes in airway opening pressure (PaO), pulmonary arterial pressure (Ppa), and weight induced by intravascular administration of substance P were examined in isolated perfused and ventilated guinea pig lungs. Administration of 1 nmol substance P without enzyme inhibitors resulted in a significant (P less than 0.01) increase in the peak PaO during ventilation from 12.4 +/- 0.5 to 22.4 +/- 2.2 cmH2O; there were small statistically insignificant increases in Ppa. The changes in PaO peaked approximately 30 s after peptide infusion and returned to preinfusion values by 5 min. In the presence of combined thiorphan (5.6 microM) and captopril (7.7 microM) the magnitude of the Pao response at 30 s (41.5 +/- 3.8 cmH2O) and at 5 min (40.0 +/- 3.6 cmH2O) after peptide infusion was significantly greater than in control lungs (P less than 0.05). The effects of substance P on PaO in the presence of the various inhibitors were not related to amount of peptide recovered in the lung effluent. Reverse-phase high-performance liquid chromatographic analysis of [3H]Pro2,4 substance P perfused through the lungs demonstrated that the major products were consistent with intact substance P, substance P 1–4, and smaller peptides; only minor amounts of products consistent with substance P 1–7, 1–9, or 3–11 were identified. These data support our previous findings showing that the physiological effects of intravascular substance P are limited by peptide degradation; the latter process, once begun, proceeds rapidly to nearly complete peptide degradation.
Airway blood flow response to eucapnic dry air hyperventilation in sheep
Authors: Parsons G. H. , Pare P. D. , White D. A. , Baile E. M.
Published: December 2017

Eucapnic hyperventilation, breathing dry air, produces a two- to fivefold increase in airway blood flow in the dog. To determine whether airway blood flow responds similarly in the sheep we studied 16 anesthetized sheep. Seven sheep (1–7) were subjected to two 30-min periods of eucapnic hyperventilation breathing 1) warm humid air [100% relative humidity (rh)] followed by 2) warm dry air [0% rh] at 40 breaths/min. To determine whether there was a dose-response effect on blood flow of increasing levels of hyperventilation of dry air, another nine sheep (8–16) were subjected to four 30-min periods of eucapnic hyperventilation breathing warm humid O2 followed by warm dry O2 at 20 or 40 breaths/min in random sequence. Five minutes before the end of each period of hyperventilation, hemodynamics, blood gases, and tracheal mucosal temperature were measured, and tracheal and bronchial blood flows were determined by injection of 15- or 50-micron-diam radiolabeled microspheres. After the last measurements had been made, all sheep were killed, and the lungs and trachea were removed for determination of blood flow to trachea, bronchi, and parenchyma. In sheep 1–7, warm dry air hyperventilation at 40 breaths/min produced an increase in blood flow to trachea (7.6 +/- 3.5 to 17.0 +/- 6.2 ml/min, P less than 0.05) and bronchi (9.0 +/- 5.4 to 18.2 +/- 8.2 ml/min, P less than 0.05) but not to the parenchyma. When blood flow was compared with the two ventilatory rates (sheep 8–16), tracheal blood flow increased (9.1 +/- 3.3 to 18.2 +/- 6.1 ml/min, P less than 0.05) at a rate of 40 breaths/min but not at 20 breaths/min.(ABSTRACT TRUNCATED AT 250 WORDS)