bluuebunny/crossref_metadata_2025 huggingface dataset:
Production of arachidonic acid metabolites by endothelial cells in hyperoxia
Authors: Jackson R. M. , Chandler D. B. , Fulmer J. D.
Published: December 2017

This study investigated the response of bovine pulmonary artery endothelial cells to incubation in hyperoxia (95% O2–5% CO2). Changes in cell number and morphology, release of lactate dehydrogenase, and production of arachidonic acid metabolites were assessed during continuous exposure of confluent endothelial monolayers to air (air-5% CO2, “controls”) or O2 (95% O2–5% CO2, “O2-exposed”) for periods of 12–72 h. Control monolayer cell numbers remained constant (approximately 2,000,000 cells/flask), whereas the number of cells in O2-exposed monolayers decreased progressively to 30% of controls (P less than 0.01) by 72 h. As assessed by radioimmunoassay, both control and O2-exposed cells produced the prostacyclin metabolite, 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), and prostaglandin F2 alpha (PGF2 alpha), but no thromboxane metabolite (TxB2) was detected. The O2-exposed cells released significantly more 6-keto-PGF1 alpha and PGF2 alpha than control cells when apparent net production rates over the entire 72-h period were compared. In addition, both control and O2-exposed (48 h) endothelial monolayers released immunoreactive leukotriene B4 (LTB4) on stimulation with calcium ionophore (10 microM A23187). As with the cyclooxygenase products, O2-exposed cells released more immunoreactive LTB4 than did controls. Both cyclooxygenase and lipoxygenase metabolites of arachidonic acid are released by cultured endothelial cells during the development of O2 toxicity.
Influence of testosterone on breathing during sleep
Authors: Schneider B. K. , Pickett C. K. , Zwillich C. W. , Weil J. V. , McDermott M. T. , Santen R. J. , Varano L. A. , White D. P.
Published: December 2017

Apneas and hypopneas during sleep occur more frequently in men than women. Disordered breathing is also reported to increase in hypogonadal men following testosterone administration. This suggests a hormonal influence on sleeping respiratory pattern. We therefore studied respiratory rhythm during sleep in 11 hypogonadal males both on and off testosterone-replacement therapy. In four subjects the anatomy (computerized tomography) and airflow resistance of the upper airway were also determined on both occasions. Sleep stage distribution and duration were unchanged following androgen administration. However, both apneas and hypopneas increased significantly during testosterone replacement so that the total number of disordered breathing events (apneas + hypopneas) per hour of sleep rose from 6.4 +/- 2.1 to 15.4 +/- 7.0 (P less than 0.05). This was a highly variable event with some subjects demonstrating large increases in apneas and hypopneas when androgen was replaced, whereas others had little change in respiration during sleep. Upper airway dimensions, on the other hand, were unaffected by testosterone. These results suggest that testosterone contributes to sleep-disordered breathing through mechanisms independent of anatomic changes in the upper airway.
Regional control of local airway heat and water vapor losses
Authors: Hanna L. M. , Scherer P. W.
Published: December 2017

The regulation of local heat and water vapor losses along the respiratory tract is examined based on a theoretical model of respiratory air conditioning and physiological data. The theoretical model is a quasi-steady one-dimensional model descriptive of the localized process of heat and water transport within the airways. During nasal breathing the model is most sensitive to the following two parameters: 1) the gradient of blood temperature along the airway wall and 2) the nasal air space volume. Thermoregulatory control of these two factors within the primary conditioning region, the upper airway, establishes the overall respiratory heat and water loss. Upper airway thermoregulation, however, also effects the heat and water demands placed on the secondary conditioning region, the tracheobronchial airways. Similar to the upper airway, the tracheobronchial airway wall temperature varies in response to changing demands. The bronchial circulation is shown to provide a major source of heat within the first several bronchial generations where the greatest heat and water fluxes within the lung are predicted to occur. Control of the bronchial blood flow may therefore directly influence the bronchoconstrictive response in asthmatics.
Blood flow and glycogen use in hypertrophied rat muscles during exercise
Authors: Armstrong R. B. , Ianuzzo C. D. , Laughlin M. H.
Published: December 2017

Previous findings suggest that skeletal muscle that has enlarged as a result of removal of synergistic muscles has a similar metabolic capacity and improved resistance to fatigue compared with normal muscle. The purpose of the present study was to follow blood flow and glycogen loss patterns in hypertrophied rat plantaris plantaris and soleus muscles during treadmill exercise to provide information on the adequacy of perfusion of the muscles during in vivo exercise. Thirty days following surgical removal of gastrocnemius muscle, blood flows (determined with radiolabeled microspheres) and glycogen concentrations were determined in all of the ankle extensor muscles of experimental and sham-operated control rats during preexercise and after 5–6 min of treadmill exercise at 15 m/min. There were no differences (P greater than 0.05) in blood flows per unit mass or glycogen concentrations between control and hypertrophied plantaris or soleus muscles at either time, although both muscles were larger (P less than 0.05) in the experimental group (plantaris: 95%; soleus: 40%). None of the other secondary ankle extensor muscles (tibialis posterior, flexor digitorum longus or flexor hallicus longus) hypertrophied in response to removal of gastrocnemius. These results provide indirect evidence that O2 delivery in the enlarged muscles is not compromised during low-intensity treadmill exercise due to limited perfusion.
Effects of extracellular calcium on canine tracheal smooth muscle
Authors: Gunst S. J. , Pisoni J. M.
Published: December 2017

Strips of canine tracheal smooth muscle were studied in vitro to determine the effects of changes in the extracellular calcium (Cao) concentration on tonic contractions induced by acetylcholine and 5-hydroxytryptamine. Strips were contracted with graded concentrations of the above agents in 2.4 mM Ca, after which CaCl2 was administered to achieve final concentrations of 5.0, 10.0, and 20.0 mM. Increases in Cao to 5 mM or above caused significant relaxation of muscles contracted with 5-hydroxytryptamine but did not significantly relax muscles contracted with acetylcholine. Increases in Cao also caused significant relaxation of muscles contracted with low concentrations of K+ (20 or 30 mM). However, in 60 or 120 mM K+, increases in Cao resulted predominantly in muscle contraction. Inhibition of the Na+-K+-ATPase by ouabain (10(-5) M) or K+ depletion reversed the effects of Cao from relaxation to contraction in tissues contracted with 5-hydroxytryptamine. Increases in Cao also caused contraction rather than relaxation in the presence of verapamil (10(-6) M). We conclude that calcium has both excitatory and inhibitory effects on the contractile responses of canine tracheal smooth muscle. The inhibitory effects of Ca2+ appear to be linked to the activity of the membrane Na+-K+-ATPase.
Effects of alveolar pressure on lung angiotensin-converting enzyme function in vivo
Authors: Toivonen H. J. , Catravas J. D.
Published: December 2017

Angiotensin-converting enzyme lines the luminal surface of pulmonary capillary endothelial cells. The metabolism of its synthetic substrate, 3H-benzoyl-L-phenylalanyl-L-alanyl-L-proline ([3H]BPAP) has been used as an indicator of pulmonary microvascular function. Because the flow-volume status of the pulmonary capillaries is dependent on intra-alveolar pressure, we have studied the effects of airway pressure on endothelial plasmalemmal angiotensin-converting enzyme function in rabbit lungs in vivo. Static inflation of the lungs to a pressure of 0 or 5 Torr did not change percent transpulmonary metabolism and Amax/Km ratio (defined as E X Kcat/Km and thus, under normal conditions, an indirect measure of perfused endothelial luminal surface area) compared with control measurements during conventional mechanical ventilation. When the inflation pressure was increased to 10 Torr, percent metabolism of [3H]BPAP remained unaltered but Amax/Km decreased to 60% of the control value. This decrease was in close relation to the decrease in pulmonary blood flow. Addition of 5 cmH2O positive end-expiratory pressure (PEEP) to the mechanical ventilation also decreased Amax/Km values and pulmonary blood flow but did not influence percent metabolism of [3H]BPAP. These results suggest that the detected alterations in apparent enzyme kinetics were more likely due to hemodynamic changes than to alterations in angiotensin-converting enzyme function. Thus high static alveolar pressures as well as PEEP probably reduced the fraction of perfused microvessels as reflected in changes in Amax/Km ratios. This information should prove useful in interpreting the response of pulmonary endothelial enzymes to injury.
Diffusion-related differences in elimination of inert gases from the lung
Authors: Robertson H. T. , Whitehead J. , Hlastala M. P.
Published: December 2017

Partial pressures of intravenously infused acetylene, Freon 22, and isoflurane (gases with similar solubilities in blood but differing molecular weights) were compared in arterial and mixed venous blood and mixed expired gas of 13 anesthetized mongrel dogs to determine whether gas molecular weight influenced gas exchange. Analysis of covariance was used to account for the variables of ventilation-perfusion ratio, partition coefficient, and experimental run before individual gas effects were sought. A gas effect difference was observed such that the arterial fractional retention of isoflurane (mol wt 184.5) would be 12% higher than that of acetylene (mol wt 26) if the two gases had identical partition coefficients. This effect was neither significantly increased by positive end-expiratory pressure nor decreased by high-frequency oscillatory ventilation. To test whether the individual gas effect was greater with gases with disparate erythrocyte and plasma partition coefficients, the exchange of ethyl iodide (erythrocyte-to-plasma solubility ratio 8.1) and diethyl ether (solubility ratio 0.95) was compared in five dogs. A larger difference between the elimination of the two gases was observed than predicted from the differences in molecular weight. The observed individual gas effect appears to be diffusion related, influenced both by the molecular weight of a gas and its erythrocyte-plasma partition coefficient ratio.
Dynamics of mammalian thermoregulation and its circadian component
Authors: Iberall A. S.
Published: December 2017

This note attempts to focus a physical theory for the dynamics of mammalian thermoregulation, its relation to thermodynamic near-equilibrium, and its relation to a circadian component of that regulation. As such, it is an extension of the analysis and discussion carried on in earlier references. That earlier analysis is tested and extended by the use of two additional data sets not found in the earlier work.
Central role of cyclooxygenase in the response of canine peripheral airways to antigen
Authors: Kleeberger S. R. , Kolbe J. , Adkinson N. F. , Peters S. P. , Spannhake E. W.
Published: December 2017

We studied the effects of antigen aerosol challenge on the airways of the canine peripheral lung and examined the roles of cyclooxygenase products, histamine, and cholinergic activity in the responses. One-minute deliveries of 1:10,000 or 1:100,000 concentrations of Ascaris suum antigen aerosol through a wedged bronchoscope resulted in mean maximal increases in collateral system resistance (Rcs) of 415 and 177%, respectively, after 4–8 min. Repeated antigen challenge (1:100,000) resulted in significantly decreased responsiveness to antigen after the initial exposure (P less than 0.005). Bronchoalveolar lavage fluid obtained from the isolated, challenged segment had a significant increase in mean (+/- SE) prostaglandin D2 (PGD2) concentration vs. control (222.0 +/- 65.3 vs. 72.7 +/- 19.5 pg/ml; P less than 0.05); histamine concentrations were variable and not significantly different (4.1 +/- 2.6 vs. 1.2 +/- 0.2 ng/ml; P greater than 0.05). In nine experiments, cyclooxygenase inhibition significantly attenuated the antigen-induced increase in Rcs by 53.4% (P less than 0.001), and the concentration of PGD2 in lavage fluid was reduced by 96.0% (P less than 0.01). Blockade of histamine H1-receptors (n = 8) or cholinergic receptors (n = 7) did not significantly affect the airway response (P greater than 0.05). These data indicate that the canine peripheral lung responds in a dose-dependent manner to antigen aerosol challenge and exhibits characteristics of antigen tachyphylaxis. Results also suggest that cyclooxygenase products play a central role in the acute bronchoconstrictive response of the lung periphery.
Respiratory timing during NREM sleep in patients with occlusive sleep apnea
Authors: Onal E. , Lopata M.
Published: December 2017

To study respiratory timing mechanisms in patients with occlusive apnea, inspiratory and expiratory times (TI and TE) were calculated from the diaphragmatic electromyogram obtained in seven patients during non-rapid-eye-movement (NREM) sleep. Peak diaphragmatic activity (EMGdi) had a curvilinear relationship with TI during the ventilatory and occlusive phases such that TI shortened as EMGdi decreased during the ventilatory phase (r = 0.87, P less than 0.05) and it prolonged as EMGdi increased during the occlusive phase (r = 0.89, P less than 0.02). However, EMGdi vs. TI for the occlusive phase was shifted to the right of that for the ventilatory phase, reflecting the relatively longer TI during upper airway occlusion. TI also had a linear relationship with pleural pressure (r = 0.94, P less than 0.001) that remained unchanged during the ventilatory and occlusive phases such that it prolonged as negative inspiratory pressure increased. These results indicate that respiratory timing is continuously modified in patients with occlusive apnea as inspiratory neural drive fluctuates during NREM sleep and suggest that this modification is due to the net effects of changing inspiratory neural drive and afferent input predominantly from upper airway mechanoreceptors.
Hemoglobin concentrations and blood gas tensions of free-diving Weddell seals
Authors: Qvist J. , Hill R. D. , Schneider R. C. , Falke K. J. , Liggins G. C. , Guppy M. , Elliot R. L. , Hochachka P. W. , Zapol W. M.
Published: December 2017

Arterial blood gas tensions, pH, and hemoglobin concentrations were measured in four free-diving Weddell seals Leptonychotes weddelli. A microprocessor-controlled sampling system enabled us to obtain 24 single and 31 serial aortic blood samples. The arterial O2 tension (PaO2) at rest [78 +/- 13 (SD) Torr] increased with diving compression to a maximum measured value of 232 Torr and then rapidly decreased to 25-35 Torr. The lowest diving PaO2 we measured was 18 Torr just before the seal surfaced from a 27-min dive. A consistent increase of arterial hemoglobin concentrations from 15.1 +/- 1.10 to 22.4 +/- 1.41 g/100 ml (dives less than 17 min) and to 25.4 +/- 0.79 g/100 ml (dives greater than 17 min) occurred during each dive. We suggest that an extension of the sympathetic outflow of the diving reflex possibly caused profound contraction of the Weddell seal's very large spleen (0.89% of body wt at autopsy), although we have no direct evidence. This contraction may have injected large quantities of red blood cells (2/3 of the total) into the seal's central circulation during diving and allowed arterial O2 content to remain constant for the first 15-18 min of long dives. The increase of arterial CO2 tensions during the dive and the compression increase of arterial N2 tensions were also moderated by injecting red blood cells sequestered at ambient pressure. After each dive circulating red blood cells are oxygenated and rapidly sequestered, possibly in the spleen during the first 15 min of recovery.
Effect of hemorrhage on regional morphometric indexes of cerebral capillarity
Authors: Grover G. J. , Francois-Dainville E. , Buchweitz E. , Weiss H. R.
Published: December 2017

This study was performed to determine whether the brain can increase the number of perfused capillaries and arterioles supplying it regionally during hemorrhage. This was done using a technique to simultaneously determine total and perfused regional arteriolar and capillary morphology. Conscious Long-Evans rats served as unbled controls or were bled 65 mmHg or to 40–45 mmHg and stabilized for 30 min. Regional cerebral blood flow was determined using [14C]iodoantipyrine in half of these animals and fluorescein isothiocyanate-dextran was injected in the other half for determination of perfused cerebral microvascular morphometric indexes. The total microvasculature was labeled postmortem via an alkaline phosphatase stain. Regional cerebral blood flow was significantly increased in animals bled to 65 mmHg. During hemorrhage to 40–45 mmHg, cerebral blood flow was reduced 50% (from 59 +/- 28 to 26 +/- 11 ml X min-1 X 100 g-1, mean +/- SD) with no regional redistribution. For all treatments, total capillary density ranged from 400 to 500 capillaries/mm2, and in controls 47% were perfused. Animals bled to 65 mmHg did not mobilize their unperfused microvascular reserve even though they showed a slight tendency to do so. During hemorrhage to 40–45 mmHg, this percent increased significantly to 57% with the largest increase occurring in the pons. Approximately 51% of arterioles were perfused in controls and this was not different compared with the percent perfused during hemorrhage. Despite the overall lack of mobilization of unperfused arterioles, some regions within the brain significantly mobilized their reserves with severe hemorrhage, e.g., hippocampus (78%), hypothalamus (67%), and medulla (73%).(ABSTRACT TRUNCATED AT 250 WORDS)
Skeletal muscle hypertrophy in rats having growth hormone-secreting tumor
Authors: Riss T. L. , Novakofski J. , Bechtel P. J.
Published: December 2017

Plantaris muscle hypertrophy resulting from surgical ablation of the synergistic gastrocnemius muscle was compared between nontumor- and GH3 tumor-bearing rat groups (n = 8–10). GH3 cells (10(6)) were subcutaneously injected into 150-g female Wistar-Furth rats to initiate the tumor. After 17 days, the tumor-bearing rats gained 5.7 g body wt/day compared with 2.0 for the nontumor-bearing rats. The left gastrocnemius muscle was surgically removed from both nontumor and tumor groups. The gastrocnemius was removed from the tumor group after an increased growth rate was achieved. Seven days after surgery, the animals were killed and plantaris muscles were removed. The wet weight of the left plantaris muscle increased 45.6 and 44.0% over the unoperated contralateral control (right side) in the nontumor and tumor groups, respectively. The right control plantaris muscle in the tumor group was 63% heavier than the right control plantaris from the nontumor group; however, the proportion of body weight for plantaris was similar between the two groups. The effect of gastrocnemius ablation and tumor treatment on plantaris weight was additive, and the percent increase over the unoperated contralateral control side was similar between the two groups. These data demonstrate that skeletal muscle hypertrophy occurs in adult animals in which growth has been stimulated by a growth hormone-secreting tumor and could suggest that the muscle growth response caused by the tumor is operating by a mechanism different than work-induced hypertrophy.
Pulmonary gas exchange in humans during normobaric hypoxic exercise
Authors: Hammond M. D. , Gale G. E. , Kapitan K. S. , Ries A. , Wagner P. D.
Published: December 2017

Previous studies (J. Appl. Physiol. 58: 978–988 and 989–995, 1985) have shown both worsening ventilation-perfusion (VA/Q) relationships and the development of diffusion limitation during heavy exercise at sea level and during hypobaric hypoxia in a chamber [fractional inspired O2 concentration (FIO2) = 0.21, minimum barometric pressure (PB) = 429 Torr, inspired O2 partial pressure (PIO2) = 80 Torr]. We used the multiple inert gas elimination technique to compare gas exchange during exercise under normobaric hypoxia (FIO2 = 0.11, PB = 760 Torr, PIO2 = 80 Torr) with earlier hypobaric measurements. Mixed expired and arterial respiratory and inert gas tensions, cardiac output, heart rate (HR), minute ventilation, respiratory rate (RR), and blood temperature were recorded at rest and during steady-state exercise in 10 normal subjects in the following order: rest, air; rest, 11% O2; light exercise (75 W), 11% O2; intermediate exercise (150 W), 11% O2; heavy exercise (greater than 200 W), 11% O2; heavy exercise, 100% O2 and then air; and rest 20 minutes postexercise, air. VA/Q inequality increased significantly during hypoxic exercise [mean log standard deviation of perfusion (logSDQ) = 0.42 +/- 0.03 (rest) and 0.67 +/- 0.09 (at 2.3 l/min O2 consumption), P less than 0.01]. VA/Q inequality was improved by relief of hypoxia (logSDQ = 0.51 +/- 0.04 and 0.48 +/- 0.02 for 100% O2 and air breathing, respectively). Diffusion limitation for O2 was evident at all exercise levels while breathing 11% O2.(ABSTRACT TRUNCATED AT 250 WORDS)
Skeletal muscle characteristics in sedentary black and Caucasian males
Authors: Ama P. F. , Simoneau J. A. , Boulay M. R. , Serresse O. , Theriault G. , Bouchard C.
Published: December 2017

Twenty-three male Black African and 23 male Caucasian subjects, ascertained as sedentary, participated in this study designed to determine whether there were differences in skeletal muscle histochemical and biochemical characteristics between racial groups. Muscle fiber type proportions (I, IIa, and IIb), fiber areas and activities of several enzyme markers of different energy metabolic pathways were determined from a biopsy of the vastus lateralis. Results indicated that Caucasians had a higher percent type I (8%, P less than 0.01) and a lower percent type IIa (6.7%, P less than 0.05) fiber proportions than Africans. No significant differences were observed between the two racial groups in the type IIb fiber proportion or in the three fiber type areas. Enzymes catalyzing reactions in phosphagenic [creatine kinase (CK)] and glycolytic [hexokinase (HK), phosphofructokinase (PFK), and lactate dehydrogenase (LDH)] metabolic pathways had significantly higher activities (about 30–40%) in the Black African group than in the Caucasian group (P less than 0.01). No significant difference was noted in the activities of oxidative enzymes [malate dehydrogenase (MDH), oxoglutarate dehydrogenase (OGDH), and 3-hydroxyacyl-CoA dehydrogenase (HADH)]. Consequently, the PFK/OGDH ratio was significantly elevated in Africans (P less than 0.05). The racial differences observed between Africans and Caucasians in fiber type proportion and enzyme activities of the phosphagenic and glycolytic metabolic pathways may well result from inherited variation. These data suggest that sedentary male Black individuals are, in terms of skeletal muscle characteristics, well endowed for sport events of short duration.
Changes in chest wall structure and elasticity in elastase-induced emphysema
Authors: Thomas A. J. , Supinski G. S. , Kelsen S. G.
Published: December 2017

The present study examined the effects of elastase-induced emphysema on the structure and elasticity of the chest wall. Specifically, we examined the passive pressure-volume relationship of the intact chest wall in anesthetized animals and the stress-strain relationship of the isolated rib cage devoid of respiratory musculature. The structure of the isolated rib cage was assessed by measuring its circumferential, anterior-posterior, and transverse dimensions, the angles of articulation of the ribs at the costovertebral and sternochondral joints, and the length of the sternum and individual ribs. Studies were performed in 10 Syrian Golden hamsters, 26–27 wk after intratracheal injection of elastase, and 9 saline-injected hamsters that served as controls. Mean functional residual capacity of emphysematous animals was 239% of the value obtained in control animals. In emphysematous animals, the pressure-volume curve of the chest wall was shifted parallel and to the left of the curve obtained in controls. That is, at any given esophageal pressure, lung volume was significantly greater in emphysematous animals compared with controls, but the slope of the pressure-volume relationship was similar in the two groups. In the relaxed position, the circumference, anterior-posterior, transverse, and rostral-caudal dimensions of the thorax were significantly greater in emphysematous than control animals. Although the length of the thoracic spinal column was the same in both groups, the length of the ribs and sternum were greater in emphysematous animals and the angles of articulation of the ribs with the vertebrae and sternum were altered.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of expiratory loading on expiratory duration and pulmonary stretch receptor discharge
Authors: Davenport P. W. , Wozniak J. A.
Published: December 2017

Slowly adapting pulmonary stretch receptors have been hypothesized to be the afferents mediating the vagally dependent, volume-related prolongation of expiratory time (TE) during expiratory loading. It has been further suggested that the vagal component of this prolongation of TE is due to the temporal summation of pulmonary stretch receptor (PSR) activity during expiratory loading. This hypothesis was tested in rabbits exposed to resistive and elastic single-breath expiratory loading while PSR′s were simultaneously recorded. Both types of loads resulted in a decreased expired volume (VE) and increased expiratory duration (TE). The TE for resistive loads were significantly greater than for elastic loads for equivalent VE. Thus two different VE-TE relationships were found for resistive and elastic loads. When TE was plotted against the area under the expired volume trajectory, a single linear relationship was observed. PSR activity recorded during expiratory loading increased as VE decreased and TE increased. A single linear relationship resulted when the number of PSR spikes during the expiration was plotted against the associated TE for all types of loads. These findings demonstrate that the volume-related prolongation of TE with single-breath expiratory loads is associated with an increase in PSR discharge. These results support the hypothesis that the vagal component of load-dependent prolongation of TE is a function of both the temporal and spatial summation of PSR activity during the expiratory phase.
Physiological mechanisms contributing to increased interleukin-1 secretion
Authors: Cannon J. G. , Evans W. J. , Hughes V. A. , Meredith C. N. , Dinarello C. A.
Published: December 2017

Interleukin-1 (IL-1) is a monocyte-derived polypeptide that mediates many host defense adaptations to environmental and infectious stresses. This investigation was intended to characterize further IL-1 activity found in human plasma following exercise (3) and to identify physiological initiators of IL-1 secretion. IL-1 activity was measured by the ability of plasma fractions to stimulate lymphocyte proliferation. This activity appeared in plasma several hours after exercise on a cycle ergometer (1 h at 60% of aerobic capacity, n = 8 subjects) and was neutralized with a specific antiserum to human IL-1. The hypothesis that IL-1 release from monocytes was initiated by phagocytosis of material from cells damaged by exercise was tested. The increase in IL-1 activity did not correlate significantly (r = 0.55) with creatine kinase activity, a marker for release of intracellular proteins into the circulation, and IL-1 secretion by monocytes was not stimulated by incubation with red blood cell lysates in vitro. Thus the stimulus for IL-1 secretion did not appear to be related to a scavenging function of monocytes. The possibility that IL-1 secretion may be mediated by stress hormones associated with exercise was examined. IL-1 secretion by monocytes was increased up to 48 +/- 18% (P less than 0.01) by addition of physiological concentrations of epinephrine in vitro. Low concentrations of hydrocortisone (1 ng/ml) also augmented IL-1 secretion by 58 +/- 20%. Higher concentrations in the physiological range had no effect, and combinations of epinephrine and hydrocortisone suppressed IL-1 secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of mean airway pressure on gas transport during high-frequency ventilation in dogs
Authors: Yamada Y. , Venegas J. G. , Strieder D. J. , Hales C. A.
Published: December 2017

In 10 anesthetized, paralyzed, supine dogs, arterial blood gases and CO2 production (VCO2) were measured after 10-min runs of high-frequency ventilation (HFV) at three levels of mean airway pressure (Paw) (0, 5, and 10 cmH2O). HFV was delivered at frequencies (f) of 3, 6, and 9 Hz with a ventilator that generated known tidal volumes (VT) independent of respiratory system impedance. At each f, VT was adjusted at Paw of 0 cmH2O to obtain a eucapnia. As Paw was increased to 5 and 10 cmH2O, arterial PCO2 (PaCO2) increased and arterial PO2 (PaO2) decreased monotonically and significantly. The effect of Paw on PaCO2 and PaO2 was the same at 3, 6, and 9 Hz. Alveolar ventilation (VA), calculated from VCO2 and PaCO2, significantly decreased by 22.7 +/- 2.6 and 40.1 +/- 2.6% after Paw was increased to 5 and 10 cmH2O, respectively. By taking into account the changes in anatomic dead space (VD) with lung volume, VA at different levels of Paw fits the gas transport relationship for HFV derived previously: VA = 0.13 (VT/VD)1.2 VTf (J. Appl. Physiol. 60: 1025–1030, 1986). We conclude that increasing Paw and lung volume significantly decreases gas transport during HFV and that this effect is due to the concomitant increase of the volume of conducting airways.
Firing properties and hypercapnic responses of single phrenic motor axons in the rat
Authors: Kong F. J. , Berger A. J.
Published: December 2017

Inspiratory phase activity was recorded from 33 phrenic motoneuron (PM) axonal fibers in anesthetized, vagotomized, artificially ventilated adult rats. During control conditions (no inspired CO2 added), the population of PM fibers could be separated into early and late onset types based on the time of firing onset relative to the onset of whole phrenic nerve activity. Mean discharge frequencies of both types were not significantly different. Compared with late PM′s, early PM′s had more spikes per inspiration, fired for a longer period, and the last spike occurred later and during the postinspiratory period. Further, the mean minimal interspike interval was shorter for early PM′s than for late PM′s. Increasing inspired CO2 to 0.03 and 0.05 resulted in earlier firing onsets and a greater number of spikes per inspiration, particularly for late PM′s. Increases in mean firing frequency occurred for both PM types. Mean minimal interspike intervals for both types of PM′s showed progressive reductions as CO2 rose. For almost all of the firing properties examined in this study, responses of rat PM axons were similar to those previously reported for the cat.
Cat lung hemodynamics: comparison of experimental results and model predictions
Authors: Krishnan A. , Linehan J. H. , Rickaby D. A. , Dawson C. A.
Published: December 2017

Commonly, attempts have been made to learn about the structure and function of the pulmonary vascular bed from measurements of arterial and venous pressures and blood flow rate under steady-state conditions (e.g., from pressure vs. flow data) or dynamic conditions (e.g., from vascular occlusion data). Zhuang et al. (J. Appl. Physiol. 55: 1341–1348, 1983) have presented a detailed model of steady-state cat lung hemodynamics based on direct measurements of anatomical and elasticity data. This model provides an opportunity to better understand the information content of the hemodynamic data. Therefore, in the present study we carried out a series of steady-state and dynamic experiments on isolated cat lungs. We then compared the results with those predicted by the model. We found that the model provided a good fit to the steady-state data. However, to fit the dynamic data, some modifications were necessary to account for the viscous behavior of the vessel walls and to move the first moment of the distribution of vascular resistance toward the arterial end of the vascular bed relative to that of the distribution of vascular compliance. Due to the sensitivity of the vascular resistance to small changes in vessel diameters and branching ratio, the modifications in morphometry represent small changes in morphometric data and are probably within the range of uncertainty in such data. The modifications had little effect on the steady-state model simulations but substantially improved the dynamic model simulations, suggesting that the dynamic data are quite sensitive to small changes in the relative distributions of vessel diameters and elasticity.
Transendothelial albumin flux: evidence against asymmetric transport
Authors: Siflinger-Birnboim A. , Del Vecchio P. J. , Cooper J. A. , Malik A. B.
Published: December 2017

We examined the recent proposition (Circ. Res. 57: 903–905, 1985) that the interstitium-to-luminal transport of albumin is an active phenomenon. Studies were made using cultured bovine and sheep pulmonary-artery endothelial cells. The transendothelial 125I-albumin flux from the luminal-to-abluminal side was compared with the flux from the abluminal-to-luminal side. The endothelial cells were grown to confluence on gelatinized-polycarbonated filters separating the abluminal from the luminal compartments. The albumin concentration in each compartment was 1 g/100 ml to equalize the oncotic pressure gradients. The effect of hydrostatic pressure was eliminated by maintaining equal fluid levels in both compartments. The transendothelial albumin flux across the monolayer was measured by adding the 125I-albumin tracer either on the luminal or the abluminal side. A double-isotope method was also used to study bidirectional transendothelial flux of albumin at the same time for the same cultured endothelium. The results indicated that albumin flux from the luminal-to-abluminal side was equal to the flux from the abluminal-to-luminal side. Both bovine and sheep pulmonary artery endothelial cells in culture behave symmetrically for albumin, suggesting that albumin is not actively transported from the interstitium to the lumen.
Muscle soreness and intramuscular fluid pressure: comparison between eccentric and concentric load
Authors: Friden J. , Sfakianos P. N. , Hargens A. R.
Published: December 2017

This study investigates the dynamic and resting intramuscular pressures associated with eccentric and concentric exercise of muscles in a low-compliance compartment. The left and righ leg anterior compartments of eight healthy males (ages 22–32 yr) were exercised by either concentric or eccentric contractions of the same load (400 submaximal contractions at constant rate, 20/min for 20 min at a load corresponding to 15% of individual maximal dorsiflexion torque). Tissue fluid pressures were measured with the slit-catheter technique before, during, and after the exercise. Average peak intramuscular pressure generated during eccentric exercise (236 mmHg) was significantly greater than during concentric exercise (157 mmHg, P less than 0.001). Peak isometric contraction pressure in the eccentrically exercised compartment was significantly higher both within 20 min postexercise and on the second postexercise day (P less than 0.001). Resting pressure 2 days postexercise was significantly higher on the eccentrically exercised side (10.5 mmHg) compared with the concentrically exercised (4.4 mmHg, P less than 0.05). The ability to sustain tension during postexercise isometric contractions was impaired on the “eccentric” side. Soreness was exclusively experienced in the eccentrically exercised muscles. We conclude that eccentric exercise causes significant intramuscular pressure elevation in the anterior compartment, not seen following concentric exercise, and that this may be one of the factors associated with development of delayed muscle soreness in a tight compartment.
Acid-base effects of altering plasma protein concentration in human blood in vitro
Authors: Rossing T. H. , Maffeo N. , Fencl V.
Published: December 2017

We altered the concentration of plasma proteins in human blood in vitro by adding solutions with [Na+], [K+], and [Cl-] resembling those in normal blood plasma, either protein-free or with a high concentration of human albumin. After equilibrating the samples with a gas containing 5% CO2-12% O2–83% N2 at 37 degrees C, we measured pH, PCO2, and PO2; in separated plasma, we determined the concentrations of total plasma proteins and albumin and of the completely dissociated electrolytes (strong cations Na+, K+, Mg2+ and anions Cl-, citrate3-). With PCO2 nearly constant (mean = 35.5 Torr; coefficient of variation = 0.02), lowering plasma protein concentration produced a metabolic alkalosis, whereas increasing plasma albumin concentration gave rise to a metabolic acidosis. These acid-base disturbances occurred independently of a minor variation in the balance between the sums of strong cations and anions. We quantified the dependence of several acid-base variables in plasma on albumin (or total protein) concentration. Normal plasma proteins are weak nonvolatile acids. Although their concentration is not regulated as part of acid-base homeostasis, hypoproteinemia and hyperalbuminemia per se produce alkalosis and acidosis, respectively.
Neutrophil depletion does not prevent lung edema after endotoxin infusion in goats
Authors: Winn R. , Maunder R. , Chi E. , Harlan J.
Published: December 2017

Neutropenia was produced in goats by injection of either nitrogen mustard, (1.5 mg/kg) or hydroxyurea (200 mg X kg-1 X day-1). A nitrogen mustard (M + E) group (n = 6), a hydroxyurea (H + E) group (n = 5), and a control (E) group (n = 7) were given 1-h infusions of endotoxin (5 micrograms/kg total dose), then monitored for up to 5 h. Postmortem extravascular lung water (EVLW) was significantly higher in the M + E group (14.2 +/- 4.4 ml/kg) and the E group (11.9 +/- 3.9 ml/kg) when compared with a normal control (6.6 +/- 1.3 ml/kg) group that did not receive endotoxin. EVLW in a group made neutropenic with nitrogen mustard (6.7 +/- 1.3 ml/kg) and the H + E (7.9 +/- 1.5 ml/kg) groups were not statistically different from each other or from normal controls. Circulating neutrophil counts averaged 32 +/- 42 cells/microliter in the M + E group and 180 +/- 210 cells/microliter in the H + E group. Only minimal histological changes were seen in the H + E group, but the E and M + E lungs had severe pulmonary edema. We conclude that neutrophils are not required for increased EVLW and decreased arterial O2 partial pressure after endotoxin infusion, and hydroxyurea prevents at least part of the pulmonary edema after endotoxin by a mechanism that is not neutrophil dependent.
Effect of inspiratory resistive loading on control of ventilation during progressive exercise
Authors: D'Urzo A. D. , Chapman K. R. , Rebuck A. S.
Published: December 2017

Eight healthy volunteers performed gradational tests to exhaustion on a mechanically braked cycle ergometer, with and without the addition of an inspiratory resistive load. Mean slopes for linear ventilatory responses during loaded and unloaded exercise [change in minute ventilation per change in CO2 output (delta VE/delta VCO2)] measured below the anaerobic threshold were 24.1 +/- 1.3 (SE) = l/l of CO2 and 26.2 +/- 1.0 l/l of CO2, respectively (P greater than 0.10). During loaded exercise, decrements in VE, tidal volume, respiratory frequency, arterial O2 saturation, and increases in end-tidal CO2 tension were observed only when work loads exceeded 65% of the unloaded maximum. There was a significant correlation between the resting ventilatory response to hypercapnia delta VE/delta PCO2 and the ventilatory response to VCO2 during exercise (delta VE/delta VCO2; r = 0.88; P less than 0.05). The maximal inspiratory pressure generated during loading correlated with CO2 sensitivity at rest (r = 0.91; P less than 0.05) and with exercise ventilation (delta VE/delta VCO2; r = 0.83; P less than 0.05). Although resistive loading did not alter O2 uptake (VO2) or heart rate (HR) as a function of work load, maximal VO2, HR, and exercise tolerance were decreased to 90% of control values. We conclude that a modest inspiratory resistive load reduces maximum exercise capacity and that CO2 responsiveness may play a role in the control of breathing during exercise when airway resistance is artificially increased.
Ventilatory and blood gas dynamics at onset and offset of exercise in the pony
Authors: Powers S. K. , Beadle R. E. , Thompson D. , Lawler J.
Published: December 2017

The purpose of these experiments was to examine the temporal pattern of arterial carbon dioxide tension (PaCO2) to assess the relationship between alveolar ventilation (VA) and CO2 return to the lung at the onset and offset of submaximal treadmill exercise. Five healthy ponies exercised for 8 min at two work rates: 50 m/min 6% grade and 70 m/min 12% grade. PaCO2 decreased (P less than 0.05) below resting values within 1 min after commencement of exercise at both work rates and reached a nadir at 90 s. PaCO2 decreased maximally by 2.5 and 3.5 Torr at the low and moderate rate, respectively. After the nadir, PaCO2 increased across time during both work rates and reached values that were not significantly different (P greater than 0.05) from rest at minute 4 of exercise. Partial pressure of O2 in arterial blood and arterial pH reflected hyperventilation during the first 3 min of exercise. At the termination of exercise PaCO2 increased (1.5 Torr) above rest (P less than 0.05), reaching a zenith at 2–3 min of recovery. These data suggest that VA and CO2 flow to the lung are not tightly matched at the onset and offset of exercise in the pony and thus challenges the traditional concept of blood gas homeostasis during muscular exercise.
Caudal ventrolateral medullary cells responsive to muscular contraction
Authors: Iwamoto G. A. , Kaufman M. P.
Published: December 2017

The pressor reflex evoked by muscular contraction (exercise pressor reflex) is held to be an important mechanism in producing the cardiovascular adjustments to static exercise. Recent experiments using lesioning and metabolic labeling methods have indicated that the caudal ventrolateral medulla may be a key integrative site for the reflex evoked by muscular contraction induced by ventral root stimulation. Therefore, we sought to determine whether cells in this region could be associated with the cardiovascular reflex accompanying muscular contraction through analysis of their discharge characteristics. Eighty cells were characterized as to their response to ventral root stimulus-induced static muscular contraction, intra-arterial capsaicin (selective groups III and IV stimulus), and mechanical probing. The cells' receptive fields were also determined by mechanical probing. The receptive fields were usually large, often including all four limbs and the trunk. Four response patterns were observed to static contractions: a brisk initial discharge followed by a gradual return toward control levels (slowly adapting), a brief onset and cessation response, a brief inhibition followed by a slowly adapting discharge, and inhibition alone. Virtually all cells tested were responsive to capsaicin. Histological analysis verified the position of the recorded cells. It is suggested that the cells most likely to participate in the pressor response to muscular contraction were those cells in the general region of the lateral reticular nucleus which responded with an initial and sustained discharge and the cells that were inhibited in the region of the nucleus ambiguus (possible inhibition of vagal outflow).
Echocardiographic evaluation of space shuttle crewmembers
Authors: Bungo M. W. , Goldwater D. J. , Popp R. L. , Sandler H.
Published: December 2017

Echocardiographic measurements were obtained before and after space flight from 17 members of four shuttle crews. Measurements obtained 1 h after landing (L+0) compared with preflight values (n = 7) demonstrated an increase in heart rate (HR) (16 beats/min, 30.5%, P less than 0.05), mean arterial pressure (12%, P less than 0.05), and systemic vascular resistance (34%, P less than 0.05). End-diastolic volume index (EDVI) fell 17 ml/m2 (-23%, P less than 0.005) and stroke volume index (SVI) fell 15 ml/m2 (-28%, P less than 0.05). Repeat measurements taken 1–2 wk later (n = 17) demonstrated that HR had returned to normal (4 beats/min, P less than 0.05); however, EDVI remained significantly below preflight levels (-11%, P less than 0.005). End-systolic volume index (ESVI) was also still significantly lower (-23%, P less than 0.01). This delayed recovery occurred despite ability of the subjects to fully ambulate and exercise during the postflight period. These results indicate that spaceflight induces significant changes in heart volume affecting left ventricular function. The exact reasons for these specific changes remain unknown and will require additional measurements before, during, and after flight. The prolonged recovery period for the present subject group probably relates to their high level of aerobic conditioning.
Nonuniform effects of histamine on small pulmonary vessels in cats
Authors: Shirai M. , Sada K. , Ninomiya I.
Published: December 2017

In in vivo cat lung, using an X-ray TV system, we analyzed responses in internal diameter (ID), flow velocity, and volume flow of arteries and veins (100–500 microns ID) to histamine (8–15 micrograms/kg iv) under three conditions. With histamine alone, three types of ID response (constriction, dilatation, and no change) occurred in parallel-arranged arteries. Relative frequency and magnitude of constriction were maximum in arteries of 300–400 micron ID, whereas those of dilatation were maximum in arteries of 100–200 micron ID. In veins, relatively uniform constriction occurred. Under H2-blockade, histamine caused greater constriction than that with histamine alone in arteries and veins of 300–500 micron ID. Under beta-blockade, with histamine, ID of all vessels decreased significantly below the ID sizes under the above two conditions, and no dilatation occurred. In two parallel arteries that showed opposite ID changes to histamine, flow velocity increased, but volume flow decreased in a constricted artery while it increased in a dilated one. Those data indicated that, with histamine, qualitatively and quantitatively nonuniform ID response was induced in both parallel- and series-arranged small pulmonary arteries and, in turn, produced heterogeneous flow distribution. Factors to cause the nonuniformity may be partly explained by difference in density of H2- and beta-receptors in vascular walls.
Effect of variable parenchymal expansion on gas mixing
Authors: Wilson T. A. , Olson L. E. , Rodarte J. R.
Published: December 2017

Using implanted radiopaque markers, Hubmayr et al. (J. Appl. Physiol. 54: 1048–1056, 1983) and Olson et al. (J. Appl. Physiol. 57: 1710–1714, 1984) detected a variability in the volume changes of regions defined by the markers in intact and excised dog lungs, respectively. In dogs lying prone and in excised lobes, there is virtually no large-scale spatial organization of the variability. We interpret these data as evidence of an intrinsic heterogeneity of parenchymal expansion. The effect of variability of parenchymal expansion on gas mixing is calculated. From a statistical model, we infer that the variability of volume changes observed by Olson et al. is a result of an underlying variability with a larger magnitude at a smaller scale and that the variability at the smaller scale is large enough to explain the inefficiency of mixing observed in single-breath oxygen tests on excised dog lobes.