bluuebunny/crossref_metadata_2025 huggingface dataset:
Glycolysis is not required for fluid homeostasis in isolated rabbit lungs
Authors: Bolin R. , Guest R. J. , Albert R. K.
Published: December 2017

We investigated whether glycolysis was necessary to maintain the integrity of vascular endothelial and alveolar epithelial barriers in continually weighed isolated rabbit lungs. Lungs were perfused with a cell-free buffered salt solution, and glycolysis was inhibited with a glucose analogue (alpha-methyl glucoside, alpha-MG) or one of two glycolysis inhibitors (iodoacetic acid, IAA, or NaF). Fluid filtration rates (FFR's, the change in lung weight/time) in response to a 7.5-min zone 3 hydrostatic stress (pulmonary arterial and venous pressures raised from 8 to 15 cmH2O, alveolar pressure kept constant at 4 cm on the deflation limb) were repeatedly measured for 120 min after which the lungs were lavaged. The total protein concentration was measured in the bronchoalveolar lavage fluid (BALP). Lactate production was measured to verify inhibition of glycolysis. Lower concentrations of IAA and alpha-MG eliminated lactate production but did not affect FFR or BALP. NaF also had no effect on the FFR or BALP. Only high concentrations of IAA increased FFR and BALP, seemingly by causing nonspecific membrane injury that was unrelated to its specific effects on glycolysis. The glycolytic pathway for energy production is not necessary to maintain the integrity of the pulmonary endothelial-epithelial barrier.
Control of inspiratory duration in premature infants
Authors: Fox R. E. , Kosch P. C. , Feldman H. A. , Stark A. R.
Published: December 2017

We used single-breath mechanical loads and airway occlusions in premature infants to determine whether maturation influences the reflex control of inspiratory duration. We measured flow, volume, airway pressure, and surface diaphragmatic electromyogram (EMG) in 10 healthy preterm infants [33 +/- 1 (SD) wk gestation], 2–7 days of age. Three resistive and two elastic loads and occlusions were applied to the inspiratory outlet of a two-way respiratory valve. Application of all loads resulted in inspired volumes significantly decreased from control (P less than 0.001), and these decreases were progressive with increasing loads. Inspiratory duration (TI) was prolonged from control by all loads and occlusions when measured from the diaphragmatic EMG (neural TI) and by all but the smaller elastic load when measured from the flow tracing (mechanical TI). Similar decreases in inspired volume at the end of neural TI produced by application of both elastic and resistive loads resulted in comparable prolongation of neural TI. In contrast, for comparable volume decrements, resistive loading prolonged mechanical TI more than elastic loading (P less than 0.001). Mechanical and neural TI values of the breath after the loaded breath were unchanged from control values. Comparison of the neural volume-timing relationship in premature infants with our data in full-term infants suggests that the strength of the timing response to similar relative decrements in inspired volume is comparable. We conclude that reflex control of neural TI in premature infants depends on the magnitude of inspired volume and is independent of the volume trajectory.
Determinants of endurance in well-trained cyclists
Authors: Coyle E. F. , Coggan A. R. , Hopper M. K. , Walters T. J.
Published: December 2017

Fourteen competitive cyclists who possessed a similar maximum O2 consumption (VO2 max; range, 4.6–5.0 l/min) were compared regarding blood lactate responses, glycogen usage, and endurance during submaximal exercise. Seven subjects reached their blood lactate threshold (LT) during exercise of a relatively low intensity (group L) (i.e., 65.8 +/- 1.7% VO2 max), whereas exercise of a relatively high intensity was required to elicit LT in the other seven men (group H) (i.e., 81.5 +/- 1.8% VO2 max; P less than 0.001). Time to fatigue during exercise at 88% of VO2 max was more than twofold longer in group H compared with group L (60.8 +/- 3.1 vs. 29.1 +/- 5.0 min; P less than 0.001). Over 92% of the variance in performance was related to the % VO2 max at LT and muscle capillary density. The vastus lateralis muscle of group L was stressed more than that of group H during submaximal cycling (i.e., 79% VO2 max), as reflected by more than a twofold greater (P less than 0.001) rate of glycogen utilization and blood lactate concentration. The quality of the vastus lateralis in groups H and L was similar regarding mitochondrial enzyme activity, whereas group H possessed a greater percentage of type I muscle fibers (66.7 +/- 5.2 vs. 46.9 +/- 3.8; P less than 0.01). The differing metabolic responses to submaximal exercise observed between the two groups appeared to be specific to the leg extension phase of cycling, since the blood lactate responses of the two groups were comparable during uphill running. These data indicate that endurance can vary greatly among individuals with an equal VO2 max.
Cardiovascular and hormonal responses to swimming and running in the rat
Authors: Geenen D. , Buttrick P. , Scheuer J.
Published: December 2017

Hemodynamic and hormonal responses were studied during swimming (SW) and running (R) and in cage-confined (C) female Wistar rats at base line and 4 and 8 wk of training. Myocardial tissue levels of norepinephrine (NE) and epinephrine (EPI) were also measured at the end of 8 wk of training. Mean arterial blood pressure (BP), heart rate (HR), and blood samples for arterial lactate, plasma NE and EPI, and blood gases were obtained at rest and at 20, 40, and 60 min of exercise. After 4 wk of SW, a resting bradycardia was observed, and HR response for the remaining 4 wk was attenuated with SW compared with HR during R. BP and blood gases remained unchanged between the two groups. R resulted in increased arterial lactate concentrations compared with C and SW at base line but was not different from SW at 4 wk. SW elicited higher plasma levels of NE and EPI compared with C at base line and C and R at 4 wk. Myocardial tissue NE and EPI concentrations were markedly increased in both the left and right ventricle of the SW group compared with both R and C. These results indicate that BP and blood gases are not different between chronic R and SW and suggest a possible sympathoadrenal role in the differences observed in cardiac adaptations between R and SW.
Effects of emboli, positive-pressure ventilation, and airway water on lung water measurements
Authors: Noble W. H. , Kay J. C.
Published: December 2017

We tested the effects of microemboli, continuous positive-pressure ventilation (CPPV), and aspirated airway water on measurements of extravascular lung water by use of the technique of thermal indicator dilution (ETVL). A control group of dogs and a group of dogs in which dextran was infused created all levels of pulmonary edema. In an emboli group 0.125 g/kg of starch microemboli (63-74 micron diam) were infused. In groups with emboli and CPPV, starch emboli were infused and CPPV was then applied at 15 cmH2O. In an airway saline group measured amounts of saline were poured into the airway. In all groups postmortem pulmonary extravascular tissue weight (PETW) was determined and compared with the last ETVL. Emboli created an increased scatter when the last ETVL is compared with PETW because 1) blood trapped distal to emboli was included in the ETVL measurement, and/or 2) diffusion limitations for the thermal indicator were exceeded. Emboli and CPPV decreased ETVL/PETW. Airway saline (80 +/- 5%) was measured by ETVL. In conclusion, the ETVL technique is reliable in well-perfused lungs but loses accuracy in measuring lung water after emboli of any size or with large amounts of airway fluid.
Hypoxia-induced enhancement of nonspecific bronchial reactivity: role of leukotrienes
Authors: D'Brot J. , Ahmed T.
Published: December 2017

Because alveolar hypoxia has been shown to cause an increase of leukotrienes in lung lavage fluid, we tested the hypothesis that enhancement of nonspecific bronchial reactivity during alveolar hypoxia may be mediated by leukotrienes. In nine conscious sheep we determined specific lung resistance (sRL) before and after exposure to either air or a hypoxic gas mixture (13% O2) for 30 min. The sheep then inhaled 50 breaths of aerosolized 5% histamine solution (n = 6) or 10 breaths of 2.5% carbachol solution (n = 6) on different days, and the measurements of sRL were repeated. On subsequent days the above protocols were repeated after pretreatment with aerosolized FPL 57231 (3 ml, 1% solution), a leukotriene receptor antagonist. Inhalation of histamine and carbachol after exposure to air caused an increase in mean sRL to 337 and 342% of base line, respectively (P less than 0.05). Exposure to the hypoxic gas mixture had no effect on sRL but enhanced the histamine- and carbachol-induced increases in mean sRL to 621 and 646% of base line, respectively (P less than 0.05); these increases were significantly higher than those observed after air exposure (P less than 0.05). FPL 57231 prevented the hypoxia-induced enhancement of bronchial reactivity to histamine and carbachol without affecting the airway responsiveness to these agents after air. In another group of eight sheep, aerosolized leukotriene C4, at a dose (50 micrograms) that per se had no affect on sRL, enhanced the bronchial reactivity to carbachol. These data suggest that in sheep during alveolar hypoxia airway hyperresponsiveness may be due to the priming of airway smooth muscle by leukotrienes.
Measurement of airway mucosal perfusion and water volume with an inert soluble gas
Authors: Wanner A. , Barker J. A. , Long W. M. , Mariassy A. T. , Chediak A. D.
Published: December 2017

The purpose of this study was to develop and validate a new in vivo technique for the measurement of tracheal mucosal blood flow (Qtr) and tissue water volume (VH2O) with an inert soluble gas. The technique was based on the notion that the uptake of dimethyl ether (VDME) from an isolated tracheal segment is governed by VH2O (transient state) and Qtr (steady state). In lightly anesthetized sheep, an endotracheal tube with two cuffs placed 14.5-16.5 cm apart was placed to create a chamber into which dimethyl ether was introduced and from which VDMME into the mucosa was determined with a sensitive pneumotachograph. Mean Qtr was 1.20 ml/min (range 0.87-1.73), and mean VH2O was 1.67 ml (range 1.27-2.26). Qtr correlated with cardiac output but not with body weight or tracheal mucosal surface area determined by He dilution. VH2O did not show a correlation with any of these parameters. The response to selected pharmacological agents suggested that the measurements of Qtr and VH2O are independent of each other and from changes in tracheal diameter. Mean Qtr was 80% of mean tracheal mucosal blood flow measured with radiolabeled microspheres. We concluded that the inert soluble gas method is capable of measuring in vivo the perfusion and a water compartment of the intact tracheal mucosa.
Microvascular pressures during hypoxia in isolated lungs of newborn rabbits
Authors: Fike C. D. , Lai-Fook S. J. , Bland R. D.
Published: December 2017

The purpose of this study was to determine the sites of hypoxic vasoconstriction in lungs of newborn rabbits. We isolated and perfused with blood the lungs from 19 rabbit pups, 7-23 days old. We maintained blood flow constant, continuously monitored pulmonary arterial and left atrial pressures, and alternated ventilation of the lungs with 95% O2-5% CO2 (control), and 95% N2-5% CO2 (hypoxia). Using micropipettes and a servonulling device, we measured pressures in 20-60-micron-diam subpleural arterioles and venules during control and hypoxic conditions. We inflated the lungs to a constant airway pressure of 5-7 cmH2O and kept left atrial pressure greater than airway pressure (zone 3) during micropuncture. In eight lungs we measured microvascular pressures first during control and then during hypoxia. We reversed this order in four lungs. In seven lungs we measured microvascular pressures only during hypoxia. We found a significant increase in pulmonary arterial pressure with no change in microvascular pressures. These results indicate that the site of hypoxic vasoconstriction in lungs of newborn rabbits is arteries greater than 60 micron in diameter.
Single-breath DLCO maneuver causes cardiac output to fall during and after cycling
Authors: Miles D. S. , Gotshall R. W. , Motta M. R. , Duncan C. A.
Published: December 2017

The purpose of this study was to evaluate the influence of the single-breath pulmonary diffusing capacity (DLCO) breath-hold maneuver on central hemodynamics. Ten men (mean age 24 yr) were studied at rest, during 40 min of cycling at 40 and 60% of peak O2 uptake, and 10 min into recovery. DLCO was measured in the seated position during a 10-s breath hold at total lung capacity. At rest the breath hold caused a significant fall in stroke volume (SV, -16%) and an increase in heart rate (HR, +20%) with no change in cardiac output (Q). The resting DLCO of 36.5 ml.min-1.mmHg-1 increased by 28 and 48%, respectively, during the low- and moderate-intensity cycling. The breath hold while cycling caused a significant decrease in SV and Q, but HR did not change. Likewise, during recovery SV and Q fell with the breath hold but again HR did not change. A significant fall in systolic (-17%), diastolic (-12.5%), and mean arterial pressure (-15%) occurred during the breath hold at rest and during and after the exercise. The reduction observed in SV and blood pressure most likely reflected a decrease in venous return. The differences observed in the HR response before, compared with during and after exercise, were consistent with a resetting or shift in the operating point of the arterial baroreflex. Because blood flow fell during the exercise and recovery breath-hold maneuver, the "true" DLCO may have been underestimated during and after cycling.
Effect of alveolar hypoxia on pulmonary fluid filtration in in situ dog lungs
Authors: Homik L. A. , Bshouty Z. , Light R. B. , Younes M.
Published: December 2017

We have studied the effect of alveolar hypoxia on fluid filtration characteristics of the pulmonary microcirculation in an in situ left upper lobe preparation with near static flow conditions (20 ml/min). In six dogs (group 1), rate of edema formation (delta W/delta t, where W is weight and t is time) was assessed over a wide range of vascular pressures under two inspired O2 fraction (FIO2) conditions (0.95 and 0.0 with 5% CO2-balance N2 in both cases). delta W/delta t was plotted against vascular pressure, and the best-fit linear regression was obtained. There was no significant difference (paired t test) in either threshold pressure for edema formation [18.3 +/- 1.8 and 17.1 +/- 1.2 (SE) mmHg, respectively] or the slopes (0.067 +/- 0.008 and 0.073 +/- 0.017 g.min-1. mmHg-1.100g-1, respectively). In another seven dogs (group 2), delta W/delta t was obtained at a constant vascular pressure of 40 mmHg under four FIO2 conditions (0.95, 0.21, 0.05, and 0.0, with 5% CO2-balance N2). Delta W/delta t for the four conditions averaged 0.60 +/- 0.11, 0.61 +/- 0.11, 0.61 +/- 0.10, and 0.61 +/- 0.10 (SE) g.min-1.mmHg-1.100g-1, respectively. No significant differences (ANOVA for repeated measures) were noted. We conclude that alveolar hypoxia does not alter the threshold for edema formation or delta W/delta t at a given microvascular pressure.
Lipoprotein lipase in adipose tissues of rats running during cold exposure
Authors: Deshaies Y. , Arnold J. , Richard D.
Published: December 2017

This study evaluated the individual and combined effects of exercise training and intermittent cold exposure of similar energy cost on serum lipids and lipoprotein lipase (LPL) activity on epididymal white (WAT) and interscapular brown (BAT) adipose tissues of the rat. The animals were subjected daily to 2 h of treadmill running at 24 degrees C or for the same period of time at -5 degrees C, with or without exercise, for 28 days. Exercise training lowered serum triglycerides (P less than 0.01), whereas serum cholesterol was reduced by cold exposure (P less than 0.05). Cholesterol lowering occurred in the lipoproteins of lower densities. WAT weight was diminished by both treatments. Exercise training had an overall lowering effect on WAT total LPL activity (P less than 0.05), whereas cold exposure did not affect enzyme activity significantly. Exercise and intermittent cold interacted on BAT weight. Cold increased total BAT LPL activity (P less than 0.03), whereas simultaneous exercise in the cold greatly diminished this effect. Serum insulin levels were not affected by either treatment. Thus, in WAT, intermittent exposure to cold did not have any lasting effect on LPL activity, whereas exercise training decreased the latter. In contrast, exercise did not influence LPL in BAT of rats not exposed to cold but prevented the stimulation of enzyme activity induced by repeated cold exposure. These results support the notion that the regulation of LPL is tissue specific.
Effects of increased pulmonary vascular tone on gas exchange in canine oleic acid pulmonary edema
Authors: Leeman M. , Lejeune P. , Hallemans R. , Melot C. , Naeije R.
Published: December 2017

Pulmonary gas exchange was investigated before and after an increase in pulmonary vascular tone induced by administration of acetylsalicylic acid (ASA), indomethacin, or almitrine in 32 pentobarbital-anesthetized and ventilated (fraction of inspired O2 0.4) dogs with oleic acid lung injury. Pulmonary vascular tone was evaluated by five-point pulmonary arterial pressure (PAP)/cardiac index (Q) plots and intrapulmonary shunt was measured using a SF6 infusion. PAP/Q plots were rectilinear in all experimental conditions. In control dogs (n = 8), oleic acid (0.09 ml/kg iv) increased PAP over the range of Q studied (1-5 l.min-1.m-2). At the same Q, arterial PO2 fell from 186 +/- 11 to 65 +/- 8 (SE) Torr and intrapulmonary shunt rose from 5 +/- 1 to 50 +/- 6% 90 min after oleic acid injection. These changes remained stable during the generation of two consecutive PAP/Q plots. ASA (1 g iv, n = 8), indomethacin (2 mg/kg iv, n = 8), and almitrine (8 micrograms.kg-1.min-1 iv, n = 8) produced a further increase in PAP at each level of Q. ASA and indomethacin, respectively, increased arterial PO2 from 61 +/- 4 to 70 +/- 3 Torr (P less than 0.05) and from 70 +/- 6 to 86 +/- 6 Torr (P less than 0.05) and decreased intrapulmonary shunt from 61 +/- 5 to 44 +/- 4% (P less than 0.05) and from 44 +/- 5 to 29 +/- 4% (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Gaudeamus igitur
Authors: Fishman A. P.
Published: December 2017

Word is out that the American Physiological Society is about to launch a new journal entitled Lung Cellular and Molecular Physiology.
Afferent neural pathways in cough and reflex bronchoconstriction
Authors: Karlsson J. A. , Sant'Ambrogio G. , Widdicombe J.
Published: December 2017

Cough and bronchoconstriction are airway reflexes that protect the lung from inspired noxious agents. These two reflexes can be evoked both from the larynx and tracheobronchial tree and also from some extrarespiratory sites. Within the airways, certain sites are particularly sensitive to stimulation of cough (larynx and points of proximal airway branching), whereas bronchoconstriction can be triggered from the whole of the tracheobronchial tree. In the larynx, "irritant" receptors with myelinated afferents mediate cough and bronchoconstriction. Little seems to be known about laryngeal nonmyelinated afferents and their reflexes. In the tracheobronchial tree and lung, slowly adapting stretch receptors (SARs) and rapidly adapting stretch receptors (RARs) have opposing effects on airway tone, the former mediating bronchodilation and the latter bronchoconstriction. In cough, on the other hand, they operate concurrently, a mediatory role for RARs and a facilitatory role for SARs. C-fiber endings (bronchial and pulmonary) mediate bronchoconstriction. Inhalation of so-called "selective" C-fiber stimulants induces cough, but excitation of RARs has not been eliminated, and the possibility also exists that the cough is secondary to other lung actions mediated by these nerve endings. Although cough and bronchoconstriction may be mediated by the same type of receptor, they seem to have separate afferent neural pathways.
Mechanism of improvement in pulmonary gas exchange during growth in awake piglets
Authors: Escourrou P. J. , Teisseire B. P. , Herigault R. A. , Vallez M. O. , Dupeyrat A. J. , Gaultier C.
Published: December 2017

Previous studies have shown a lower arterial PO2 (PaO2) in infants and young animals than in adults. To investigate the mechanism of this impairment of gas exchange we studied 13 piglets from 12 to 65 days of age. Two days after instrumentation we measured the distribution of ventilation-perfusion ratios (VA/Q) by use of the multiple inert gas technique on awake animals. We showed that PaO2 is lower in young animals, increasing from 72 +/- 11.5 Torr before 2 wk to 102 Torr at 2 mo. This hypoxemia is due to an enlarged alveolar-arterial O2 pressure difference that significantly decreases with age. This impairment in gas exchange is not due to shunting (0.6 +/- 1.3%). Mean dead space (36 +/- 11%) was not related to age. Mean modes of perfusion and ventilation did not differ significantly between age groups. However, the dispersion of perfusion as expressed by its logSD decreased significantly with age, whereas dispersion of ventilation remained constant. Furthermore, in the young animals only, a significant difference was evidenced between measured alveolar-arterial PO2 gradient and the value predicted by the inert gas model. We therefore conclude that the impairment of gas exchange in piglets is due to two mechanisms: VA/Q mismatch and diffusion limitation for O2.
Direct measurement of static chest wall compliance in animal and human neonates
Authors: Davis G. M. , Coates A. L. , Papageorgiou A. , Bureau M. A.
Published: December 2017

The measurement of pulmonary mechanics has been developed extensively for adults, and these techniques have been applied directly to neonates and infants. However, the compliant chest wall of the infant frequently predisposes to chest wall distortion, especially when there is a low dynamic lung compliance (CL,dyn). We describe a technique of directly measuring the static chest wall compliance (Cw,st), developed initially in the newborn lamb and subsequently applied to the premature neonate with chest wall distortion. The mean CL,dyn in seven intubated newborn lambs in normoxia was 2.45 +/- 0.41 ml.cmH2O-1.kg-1, whereas Cw,st was 11.81 +/- 0.25 ml.cmH2O-1.kg-1. These values did not change significantly in seven animals breathing through a tight-fitting face mask or with hypercapnia-induced tachypnea. For the eight premature infants the mean CL,dyn was 1.35 +/- 0.36 ml.cmH2O-1.kg-1, whereas the mean Cw,st was 3.16 +/- 1.01 ml.cmH2O-1.kg-1. This study shows that, under relaxed conditions when measurements of static compliance are performed, the chest wall is more compliant than the lung. The measurement of Cw,st may thus be used to determine the contribution of the respiratory musculature in stabilizing the chest wall.
Distribution of pulmonary vascular resistance in experimental fibrosis
Authors: Michel R. P. , Hakim T. S. , Freeman C. R.
Published: December 2017

To elucidate mechanisms of pulmonary hypertension in interstitial fibrosis, we compared the left lower lobes (LLL) of six dogs in which fibrosis was induced by radiation and bleomycin with the normal right lower lobes (RLL) for 1) slope and intercept of the vascular pressure-flow (P-Q) curves, 2) segmental resistances with arterial and venous occlusion under base-line conditions, after serotonin and vasodilators, and 3) light-microscopic morphology and morphometry. We found that 1) the total volume and vascular compliance of the fibrotic LLL were five and four times less, respectively, than controls, 2) the slope and intercept of the P-Q curves in the LLL were 154.0 +/- 65.8 (SE) mmHg.l-1.min-1 and 8.2 +/- 1.5 mmHg, respectively, compared with 18.3 +/- 2.3 and 3.2 +/- 0.9 for the RLL, 3) the resistance of the arterial, middle, and venous segments in the LLL were higher than in the RLL, but middle segment resistance rose disproportionately, and 4) constriction of the arterial segment with serotonin was similar in LLL and RLL, and vasodilators were ineffective. Histologically, fibrosis involved 36% of the lung, and the capillary bed was severely obliterated. Arteries showed an increased percentage of medial and intimal thickening and peripheral muscularization; venous abnormalities were less marked. We conclude that pulmonary fibrosis increases vascular resistance mainly in the middle segment, largely by loss of tissue and obliteration of the microvasculature.
Collapse of intercellular spaces of canine tracheal mucosa by epinephrine
Authors: al-Bazzaz F. J. , Veech J. , Arenberg D.
Published: December 2017

Variations in the volume and width of lateral intercellular spaces (LICS) of dog tracheal mucosa in vitro were investigated by use of stereological and linear measurements of electron micrographs. Alterations in the volume or width of LICS were then correlated with physiological conditions and electrical parameters. LICS were quite narrow between the ciliated cells compared with those around the nonciliated dark cells (goblet, brush, and basal cells). LICS comprised 6.8 +/- 2.9% of tissue volume in preparations that were mounted in an Ussing chamber and short-circuited, whereas in unmounted and open-circuited tissues it occupied only 1 +/- 0.2% of the volume of the preparations (P less than 0.016, n = 5). The effects of stimulation of Cl secretion by 1 microM epinephrine were tested. In seven epinephrine-treated tissues LICS volume was 2.9 +/- 0.9% of total epithelial volume compared with 8.7 +/- 2.9% in control tissues (P less than 0.015). The width of LICS around dark cells in epinephrine-treated tissues was 0.42 +/- 0.06 micron compared with 0.98 +/- 0.13 micron in control tissues (P less than 0.001). The data suggest that LICS act as pliable fluid reservoirs that empty and collapse on stimulation of Cl secretion.
Hydroperoxide-induced chemiluminescence in rabbit lungs: role of arachidonic acid enzymes
Authors: Knoblauch A. L. , Paky A. , Michael J. R. , Kutner M. E. , Cadenas E. , Sies H. , Adkinson N. F. , Gurtner G. H.
Published: December 2017

Low-level chemiluminescence (C) is thought to be an index of oxidant stress. We measured the relationship between low-level C, pulmonary arterial pressure, and perfusate concentration of thromboxane B2 (TxB2) in isolated perfused rabbit lungs during challenge with tert-butyl hydroperoxide (t-bu-OOH). We also measured glutathione release as another index of oxidant stress. We found that C was correlated with each variable, suggesting that oxidant stress measured by C and by glutathione release stimulated TxB2 production and pulmonary vasoconstriction. We also investigated the contribution of active O2 metabolites produced by prostaglandin (PG) peroxidase to oxidant stress by studying the effects of t-bu-OOH before and after the use of cyclooxygenase and lipoxygenase inhibitors. We found that C was augmented after inhibition, perhaps due to metabolism of t-bu-OOH by peroxidases of both arachidonic acid (AA) metabolic pathways in the absence of their normal substrates. We studied phenylbutazone, thought to inhibit peroxidases, and AA. C during t-bu-OOH administration was not augmented after phenylbutazone and was markedly inhibited after AA administration perhaps because AA competes with t-bu-OOH. To further study the role of peroxidases we pretreated the lungs with the antioxidant dithiothreitol, which inhibits peroxidases involved in both the cyclooxygenase and lipoxygenase pathways. Dithiothreitol nearly abolished C produced by t-bu-OOH and also prevented the increased light caused by eicosatetrynoic acid. We directly tested the hypothesis that C occurred as a result of the interaction of t-bu-OOH and the cyclooxygenase and lipoxygenase enzymes; we measured C when t-bu-OOH was added to purified PGH2 synthase or soybean lipoxygenase. The combination of t-bu-OOH with PGH2 synthase or lipoxygenase led to C that was inhibited by dithiothreitol and by the antioxidant phenol. These results suggest that enzymes involved in AA metabolism can interact with t-bu-OOH and that the action of these enzymes on t-bu-OOH leads to C. The results may mean that lipid peroxides can indirectly contribute to tissue oxidant stress due to production of active O2 metabolites as by-products of their metabolism by AA peroxidases.
Effect of theophylline on the velocity of diaphragmatic muscle shortening
Authors: Supinski G. S. , Arnold J. S. , Kelsen S. G.
Published: December 2017

The present study examined the effect of theophylline on the shortening velocity of submaximally activated diaphragmatic muscle (i.e., muscles were activated by the use of a level of stimulation, 50 Hz, within the range of phrenic neural firing frequencies achieved during breathing, whereas maximum activation is achieved at 300 Hz). Experiments were performed in vitro on strips of diaphragmatic muscle obtained from 21 Syrian hamsters. Muscle shortening velocity was assessed during isotonic contractions against a range of afterloads, and Hill's characteristic equation was used to calculate velocity at zero load. In addition, unloaded shortening velocity was also measured by the slack test, i.e., from the time required for muscles to take up slack after a sudden reduction in muscle length. Theophylline (160 mg/l) increased the velocity of muscle shortening against a wide range of external loads (0-14 N/cm2) and increased the extrapolated unloaded velocity of shortening from 6.4 +/- 0.9 to 7.9 +/- 1.1 (SE) lengths/s (P less than 0.01). Theophylline reduced the time required to take up slack for any given step change in muscle length, increasing the unloaded velocity of shortening assessed by the slack test from 7.6 +/- 0.9 to 9.3 +/- 1.1 lengths/s (P less than 0.002). The effect of theophylline on diaphragmatic shortening velocity was evident at concentrations as low as 40 mg/l and increased progressively as theophylline concentrations were increased to 320 mg/l. Theophylline increased the shortening velocity of fatigued as well as fresh muscles.(ABSTRACT TRUNCATED AT 250 WORDS)
A compensation method for membrane-covered (Clark) electrodes
Authors: Barton S. A. , Hahn C. E. , Black A. M.
Published: December 2017

Membrane-covered electrodes (Clark electrodes) are widely used for monitoring blood gases, particularly PO2. A method of compensating for the inherently limited speed of response of Clark electrodes is presented. The theoretical response in the time domain is related to that in the frequency domain, and the latter is deduced from measurement of the former. Although the response functions are both infinite series, both responses are nevertheless completely defined by a single time parameter Te characteristic of the electrode under given measurement conditions. Practical verification was performed using electrodes in the double-pulsed mode, but the theory is applicable equally to direct-current-polarized and simply pulsed electrodes.
Mechanism of afterdrop after cold water immersion
Authors: Romet T. T.
Published: December 2017

It was hypothesized that if afterdrop is a purely conductive phenomenon, the afterdrop during rewarming should proceed initially at a rate equal to the rate of cooling. Eight male subjects were cooled on three occasions in 22 degrees C water and rewarmed once by each of three procedures: spontaneous shivering, inhalation of heated (45 degrees C) and humidified air, and immersion up to the neck in 40 degrees C water. Deep body temperature was recorded at three sites: esophagus, auditory canal, and rectum. During spontaneous and inhalation rewarming, there were no significant differences between the cooling (final 30 min) and afterdrop (initial 10 min) rates as calculated for each deep body temperature site, thus supporting the hypothesis. During rapid rewarming, the afterdrop rate was significantly greater than during the preceding cooling, suggesting a convective component contributing to the increased rate of fall. The rapid reversal of the afterdrop also indicates that a convective component contributes to the rewarming process as well.
Association of sex and age with responses to lower-body negative pressure
Authors: Frey M. A. , Hoffler G. W.
Published: December 2017

Responses of 21 women and 29 men (29-56 yr of age) to -50 Torr lower body negative pressure (LBNP) were examined for differences due to sex or age. Responses to LBNP were normal, including fluid shift from thorax to lower body, increased heart rate and peripheral resistance, and decreased stroke volume, cardiac output, and Heather index of ventricular function. Mean arterial blood pressure did not change. Comparison of responses of the women to responses of an age-matched subset of the men (n = 26) indicated the men had larger relative increases in calf circumference and greater increases in peripheral resistance during LBNP than the women, whereas the women experienced greater increases in thoracic impedance and heart rate. Analyses of responses of the 29 men for age-related differences indicated older subjects had greater increases in peripheral resistance and less heart rate elevation in response to LBNP (P less than 0.05 for all differences, except sex-related heart rate difference, where P less than 0.10). Based on these data and the data of other investigators, we hypothesize the age-related circulatory differences in response to LBNP are due to a reduction in vagal response and a switch to predominant sympathetic nervous system influence in older men. We cannot exclude the possibility that diminished responsiveness in the afferent arm of the baroreceptor reflex also plays a role in the attenuated heart rate response of older men to LBNP.
Inhomogeneity during deflation of excised canine lungs. I. Alveolar pressures
Authors: Warner D. O. , Hyatt R. E. , Rehder K.
Published: December 2017

Factors both intrinsic and extrinsic to the lung may cause inhomogeneity of alveolar pressures during deflation. Wilson et al. (J. Appl. Physiol. 59: 1924-1928, 1985) predicted that any such inhomogeneity would be limited by interdependence of regional expiratory flows. To test this hypothesis and to explore how the pleural pressure gradient might affect inhomogeneity of alveolar pressures, we deflated at submaximal flows excised canine lobes that first were suspended in air and then were immersed in foams that simulated the vertical gradient of pleural pressure. Interregional inhomogeneity of regional transpulmonary pressures was measured with use of an alveolar capsule technique. Flow-dependent inhomogeneity of alveolar pressures was present, with differences in alveolar pressure quickly relaxing to a constant limiting value at each flow. Foam immersion increased inhomogeneity at a given flow. We conclude that factors intrinsic to the lung cause significant inhomogeneity of alveolar pressures at submaximal expiratory flows and that this inhomogeneity is enhanced by the extrinsic gradient of pleural pressure. These observations are consistent with the interdependence of flow proposed by Wilson et al.
Volume quantification of chest wall motion in dogs
Authors: Krayer S. , Decramer M. , Vettermann J. , Ritman E. L. , Rehder K.
Published: December 2017

We employed high-speed multisliced X-ray-computed tomography to determine the relative volume contributions of rib cage (delta Vrc) and diaphragmatic motion (delta Vdi) to tidal volume (VT) during spontaneous breathing in 6 anesthetized dogs lying supine. Mean values were 40 +/- 6% (SE) for delta Vrc and 62 +/- 8% of VT for delta Vdi. The difference between VT and changes in thoracic cavity volume was taken to represent a change in thoracic blood volume (2 +/- 3% of VT). To estimate how much of delta Vrc was caused by diaphragmatic contraction and how much of delta Vdi was caused by rib cage motion, delta Vrc and delta Vdi were determined during bilateral stimulation of the C5-C6 phrenic nerve roots in the apneic dog and again during spontaneous breathing after phrenicotomy. Thoracic cavity volume (Vth) measured during hypocapnic apnea was consistently larger than Vth at end expiration, suggesting that relaxation of expiratory muscles contributed significantly to both delta Vrc and delta Vdi during spontaneous inspiration. Phrenic nerve stimulation did not contribute to delta Vrc, suggesting that diaphragmatic contraction had no net expanding action on the rib cage above the zone of apposition. Spontaneous breathing after phrenicotomy resulted in small and inconsistent diaphragmatic displacement (8 +/- 4% of VT). We conclude that the diaphragm does not drive the rib cage to inflate the lungs and that rib cage motion does not significantly affect diaphragmatic position during spontaneous breathing in anesthetized dogs lying supine.
Effect of lung inflation on diaphragmatic shortening
Authors: Road J. D. , Leevers A. M.
Published: December 2017

The effect of lung inflation on chest wall mechanics was studied in 11 vagotomized pentobarbital sodium-anesthetized dogs. Diaphragmatic shortening (percent change from initial length at functional residual capacity, %LFRC) and transdiaphragmatic pressure swings (delta Pdi) were compared with control values over a range of positive-pressure breathing that produced a maximum increase in lung volume to 40% of inspiratory capacity. There was no change in the electromyogram of the diaphragm or parasternal intercostals during positive-pressure breathing. delta Pdi and tidal volume (VT) fell to 52 +/- 3.3 and 42.5 +/- 5% (SE) of control. This was associated with a reduction in the initial resting length of 13 +/- 1.9 and 21 +/- 2.2%LFRC (SE) in the costal and crural diaphragms, respectively. Tidal diaphragmatic shortening, however, decreased to 66 +/- 7 and 57 +/- 7 and the mean velocity decreased to 78 +/- 10 and 63 +/- 8% (SE) of control for the costal and crural diaphragms, respectively. We conclude that the reduction in diaphragmatic shortening is the main determinant of the reduced delta Pdi and VT during lung inflation and relate this to what is currently known about diaphragmatic contractile properties.
Airway resistance measured in liquid-trapped guinea pig lungs by micropuncture
Authors: Lai Y. L. , Ganesan S. , Lai-Fook S. J.
Published: December 2017

We studied the relationship between bronchoconstriction and the degree of trapping in saline-filled lungs isolated from guinea pigs postmortem after rapid exsanguination. Airway resistance was measured in nine lungs, and in five lungs the site of airway narrowing was located radiographically. Animals were anesthetized with pentobarbital sodium, degassed by O2 absorption, then rapidly exsanguinated when O2 absorption was almost complete. Liquid trapping was assessed from the pressure-volume behaviour measured in saline-filled lungs. During a slow deflation from maximum volume, alveolar liquid pressure (Palv) was measured by the micropipette-servonulling method, airway opening pressure (Pao) by a strain gauge, and flow rate (Q) by weighing a reservoir connected to the airway. Airway resistance (Raw) was calculated at different lung volumes from the relationship: Raw = (Palv-Pao)/Q. In untreated lungs, Raw and fluid trapping were relatively high, and severe bronchoconstriction occurred at the level of the main stem and lobar bronchi. Nifedipine infusion reduced Raw 40-fold and decreased trapping. Raw was further reduced 10-fold and fluid trapping was minimal in lungs pretreated with nifedipine before exsanguination. Results suggest a close association between bronchoconstriction and fluid trapping in guinea pig lungs.
Effect of hemodilution on ventilatory fluctuations of pulmonary capillary blood volume
Authors: Lee J. S. , Lee L. P.
Published: December 2017

By diluting the hematocrit (Ha) in the rabbit's circulation without changing its blood volume, we found that the ventilatory-induced fluctuation (delta rho) in the density of aortic blood and Ha (which was in the range of 8-39%) are related by this linear regression: delta rho = 0.63 g/l (-0.009 + Ha). In this hemodilution experiment, the rabbits were ventilated by an intermittent positive pressure of 6 mmHg at a frequency of 30-35 cycles/min. Based on the Fahraeus effect for capillary blood flows and the dispersion of the density indicator in the rabbit's central circulation, we computed from the fluctuation of the measured density within a ventilation cycle the fluctuation of pulmonary capillary blood volume and found it to be 4.1 +/- 0.4% of the capillary blood volume for all hematocrits. Since the same fluctuation in the airway pressure was used to induce the volumetric fluctuation, its independence of Ha indicates that the hemodilution has no effect on the viscoelasticity of pulmonary capillaries.
Effect of occluded venous return on core temperature during cold water immersion
Authors: Mittleman K. D. , Mekjavic I. B.
Published: December 2017

Recent studies using inanimate and animal models suggest that the afterdrop observed upon rewarming from hypothermia is based entirely on physical laws of heat flow without involvement of the returning cooled blood from the limbs. During the investigation of thermoregulatory responses to cold water immersion (15 degrees C), blood flow to the limbs (minimized by the effects of hydrostatic pressure and vasoconstriction) was occluded in 17 male subjects (age, 29.0 +/- 3.3 yr). Comparisons of rectal (Tre) and esophageal temperature (Tes) responses were made during the 5 min before occlusion, during the 10-min occlusion period, and for 5 min immediately after the release of the cuffs (postocclusion). In the preocclusion phase, Tre and Tes showed similar cooling rates. The occlusion of blood flow to the extremities significantly arrested the cooling of Tes (P less than 0.05) with little effect on Tre. Upon release of the pressure cuffs, the returning extremity blood flow resulted in an increased rate of cooling, that was three times greater at the esophageal site (-0:149 +/- 0.052 vs. -0.050 +/- 0.026 degrees C.min-1). These results suggest that the cooled peripheral circulation, minimized during cold water immersion, may dramatically affect esophageal temperature and the complete neglect of the circulatory component to the afterdrop phenomenon is not warranted.
Intensity and duration of exercise effects on skeletal muscle cAMP, phosphorylase, and glycogen
Authors: Goldfarb A. H. , Bruno J. F. , Buckenmeyer P. J.
Published: December 2017

To gain further insights into the mechanisms regulating skeletal muscle glycogenolysis during exercise, glycogen, phosphorylase, and adenosine 3',5'-cyclic monophosphate (cAMP) were determined in fast-twitch white (FTW) and fast-twitch red (FTR) muscle from groups of rats that ran for 0, 5, 10, 15, or 30 min at either 15 or 30 m/min. Glycogen degradation demonstrated an intensity and duration response in both fiber types. cAMP increased in both fiber types by 5 min and remained elevated at all times measured. FTW muscle cAMP levels were independent of both intensity and duration of exercise. FTR muscle cAMP levels were higher from 10 to 30 min at the 30-m/min intensity compared with the 15-m/min intensity. The ratio of the activity of phosphorylase in the presence of 2 mM AMP X 100 (phosphorylase a%) remained elevated at 20–22% independent of intensity and duration in FTW muscle; however, phosphorylase a% demonstrated an intensity and duration effect in FTR muscle. Glycogenolytic rates decreased with time, even though both cAMP and phosphorylase a% remained elevated in both fiber types. These data suggest that cAMP and phosphorylase a activation can be maintained during exercise in skeletal muscle but indicate a dissociation of these factors from glycogenolysis.
Impedance of the chest wall during sustained respiratory muscle contraction
Authors: Barnas G. M. , Heglund N. C. , Yager D. , Yoshino K. , Loring S. H. , Mead J.
Published: December 2017

We measured total chest wall impedance (Zw), "pathway impedances" of the rib cage (Zrcpath), and diaphragm-abdomen (Zd-apath), and impedance of the belly wall including abdominal contents (Zbw+) in five subjects during sustained expiratory (change in average pleural pressure [Ppl] from relaxation = 10 and 20 cmH2O) and inspiratory (change in Ppl = -10 and -20 cmH2O) muscle contraction, using forced oscillatory techniques (0.5–4 Hz) we have previously reported for relaxation (J. Appl. Physiol. 66: 350–359, 1989). Chest wall configuration and mean lung volume were kept constant. Zw, Zrcpath, Zd-apath, and Zbw+ all increased greatly at each frequency during expiratory muscle contraction; increases were proportional to effort. Zw, Zrcpath, and Zd-apath increased greatly during inspiratory muscle contraction, but Zbw+ did not. Resistances and elastances calculated from each of the impedances showed the same changes during muscle contraction as the corresponding impedances. Each of the resistances decreased as frequency increased, independent of effort; elastances generally increased with frequency. These frequency dependencies were similar to those measured in relaxed or tetanized isolated muscle during sinusoidal stretching (P.M. Rack, J. Physiol. Lond. 183: 1-14, 1966). We conclude that during respiratory muscle contraction 1) chest wall impedance increases, 2) changes in regional chest wall impedances can be somewhat independent, depending on which muscles contract, and 3) increases in chest wall impedance are due, at least in part, to changes in the passive properties of the muscles themselves.
Effect of leukotrienes B4, C4, and D4 on segmental pulmonary vascular pressures
Authors: Albert R. K. , Lamm W. J. , Henderson W. R. , Bolin R. W.
Published: December 2017

Leukotrienes (LTs) C4 and D4 are vasoconstrictors and are thought to increase both systemic and pulmonary vascular permeability. However, we and others have observed that LTC4 and LTD4 cause pulmonary vasoconstriction but do not increase the fluid filtration coefficient of excised guinea pig lungs perfused with a cell-depleted perfusate. To determine what vascular segments were exposed to an LT-induced increase in intravascular hydrostatic pressure we measured pulmonary arterial (Ppa), pulmonary arterial occlusion (Po,a), venous (Po,v) and double occlusion (Pdo) pressures in isolated guinea pig lungs perfused with a cell-depleted buffered salt solution before and after injecting 4 micrograms of LTB4, LTC4, or LTD4 into the pulmonary artery. All three LTs increased airway pressures and also increased Ppa, Po,a, and Pdo. Histamine (15 micrograms) as well as serotonin (20 or 200 micrograms) had the same effect. In excised rabbit lungs, histamine and serotonin increased only Ppa, and Po,a. LTC4 had no vasoactivity. There are marked species variations with regard to the activity and site of action of histamine, serotonin, and LTC4 on the pulmonary circulation.