bluuebunny/crossref_metadata_2025 huggingface dataset:
Pulmonary interstitial compliance: a function of the osmotic constituents of the interstitium
Authors: Snashall P. D. , Keyes S. J. , Morgan B. M. , Chung K. F.
Published: December 2017

We have attempted to dehydrate the lung interstitium to determine the nature of forces holding water in that compartment. We administered furosemide with and without bovine albumin intravenously to rabbits (n = 21) 1813;24 h before they were anesthetized with pentobarbital sodium. Renal pedicels were ligated and 51Cr-labeled EDTA was injected to estimate lung interstitial water volume. After a period of equilibration the thorax was rapidly opened, and left atrial pressure was measured by direct puncture. 125I-labeled albumin was injected to label the lung vascular volume, and the rabbits were killed 3 min later. Lungs were removed and drained of blood, and extravascular water volume, interstitial volume, and dry weight were determined. Results from these rabbits were compared with a group of normal (n = 4) and overhydrated (n = 6) rabbits. We have found that lung interstitial water is removed in proportion to the change in intravascular forces. We estimate interstitial compliance to be 1.76% cmH2O-1. Our results are compatible with the hypothesis that removal of water is opposed by an increase in interstitial colloid osmotic pressure and not by a fall of hydrostatic pressure. This implies that in the normally hydrated state interstitial hydrostatic pressure is ambient.
Density dependence of maximum expiratory flow in the dog
Authors: Pedersen O. F. , Castile R. G. , Drazen J. M. , Ingram R. H.
Published: December 2017

Airway lateral and impaction pressures were measured during expiratory flow limitation in six anesthetized, vagotomized, tracheally intubated, open-chest dogs with the lungs filled with air or a mixture of 80% helium-20% oxygen (HeO2). Pressures were measured in the vicinity of equal pressure points (EPP) and choke points (CP). Maximum flow (Vmax) was ensured by demonstrating no increase in flow with a 50% increase of driving pressure. At 50% vital capacity, mean density dependence (VmaxHeO2/Vmaxair) was 1.58, which was less than 1.69 predicted for fully density-dependent flow. Transmural pressure and airway area at CP and EPP (located on air) were significantly less with HeO2 than with air. Frictional losses between the alveoli and CP were 40% greater with HeO2 than with air. These enhanced losses were mostly peripheral to the EPP. Frictional loss upstream from the EPP was 47% of the total pressure loss on air and increased to 70% on HeO2. The data at 50% VC suggest that these higher frictional losses with HeO2 resulted in decreased density dependence of Vmax due to different pressure distribution along the airway with a lower transmural pressure and smaller area at the CP.
In vivo and in vitro characteristics of eccrine sweating in patas and rhesus monkeys
Authors: Gisolfi C. V. , Sato K. , Wall P. T. , Sato F.
Published: December 2017

Biopsy specimens from the chest, palm, back, and lateral calf were obtained from three patas (413;6 kg) and two rhesus monkeys (6 and 8 kg) tranquilized with ketamine hydrochloride (10 mg/kg). The eccrine sweat glands of the specimens were subsequently isolated under a stereomicroscope and prepared for analysis. In both palmar and hairy skin (chest, lateral calf) patas eccrine glands were larger than those isolated from corresponding sites obtained from the rhesus specimens. In vitro stimulation of the patas' glands with methacholine (MCH) chloride produced a dose-dependent increase in sweating rate that was blocked by atropine. Maximal palmar sweating was comparable between the two species of monkey. Mean maximal in vitro sweating rates on the chest and lateral calf of the three patas monkeys were 3.79 and 4.6 nl. gl-1.min-1, respectively. In contrast, the in vitro sweating rate of the rhesus chest glands was negligibly small, i.e., 0.05 nl.gl-1. min-1. Maximal in vivo sweating rates measured by resistance hygrometry during exercise in a hot (40 degrees C) environment were usually synchronous, cyclic, and only slightly below maximal in vitro rates. When the monkey (patas) was already sweating, the onset and cessation of exercise produced an immediate rise and decline in sweating, respectively. At any given rectal or mean skin temperature, sweating was two- to sixfold higher in the patas compared with that of the rhesus monkey. These results indicate that the patas monkey is an excellent model for studying the physiology of sweating in humans.
Fatigue of the mammalian diaphragm in vitro
Authors: Kelsen S. G. , Nochomovitz M. L.
Published: December 2017

Diaphragm fatigue was studied in innervated diaphragm strips from 63 Sprague-Dawley rats. The experiments examined 1) the effect on the rate of diaphragmatic fatigue of increases in the diaphragm's duty cycle, i.e., the ratio of the period of diaphragmatic contraction (Ti) to the duration of a cycle of contraction and rest (Ttot) and 2) the possibility that impaired neural transmission contributed to the fatigue process. Alterations in the duty cycle of the diaphragm were simulated by varying the pattern of electrical stimuli applied cyclically to the phrenic nerve. Fatigue was assessed from the rate of fall of isometric tension when the muscle was made to contract 90 times/min. The contribution of neural element fatigue was assessed by comparing the tension during phrenic nerve stimulation to the tension developed when the muscle was stimulated directly. Increasing the duty cycle (Ti/Ttot) from 25 to 50 to 75% increased the rate of diaphragmatic fatigue progressively. Holding Ti/Ttot constant at 75%, while varying Ti and Ttot, did not affect the rate of fatigue. Increases in duty cycle appear to increase the rate of fatigue by increasing the number of times the contractile process was activated. In fatigued muscle strips diaphragmatic tension was greater in directly stimulated muscle than in muscle strips activated via the phrenic nerve. The results indicate that 1) when the breathing action of the diaphragm is simulated in vitro, increases in duty cycle accelerate the fatigue process and 2) failure of transmission of phrenic impulses to diaphragmatic muscle cells contributes to the fall in tension during fatigue.
Effect of induced erythrocythemia on hypoxia tolerance during physical exercise
Authors: Robertson R. J. , Gilcher R. , Metz K. F. , Skrinar G. S. , Allison T. G. , Bahnson H. T. , Abbott R. A. , Becker R. , Falkel J. E.
Published: December 2017

The effect of induced erythrocythemia on hypoxia tolerance during physical exercise was determined for five male mountain climbers. Treadmill testing was performed under four conditions: 1) prereinfusion, normoxia (Pre-N); 2) prereinfusion, hypoxia (Pre-H); 3) postreinfusion, normoxia (Post-N); and 4) postreinfusion, hypoxia (Post-H). An altitude of 3,566.2 m was simulated by having subjects breath a gas mixture of 13.5% O2–86.5% N2 at normal barometric pressure. Tests were administered immediately before and 24 h after autologous transfusion of 750 ml of red blood cells. Hematocrit increased from 43.3% at prereinfusion to 54.8% at postreinfusion. Hemoglobin concentration increased from 13.80 g X 100 ml-1 at prereinfusion to 17.63 g X 100 ml-1 at postreinfusion. Maximal O2 uptake (VO2 max, 1 X min-1) increased (P less than 0.05) by 12.8% (3.28 to 3.70) from Pre-N to Post-N and 13.0% (2.62 to 2.96) from Pre-H to Post-H. Treadmill performance time (s) increased (P less than 0.05) by 15.8% (793 to 918) from Pre-N to Post-N and 8.9% (687 to 748) from Pre-H to Post-H. VO2 max decreased by 20.1% from Pre-N to Pre-H and by 9.8% from Pre-N to Post-H. Treadmill time decreased by 13.4% from Pre-N to Pre-H and 5.7% from Pre-N to Post-H. The calculated change in hypoxia tolerance following reinfusion indicated that physiological altitude was improved by 463.6 m. It was concluded that induced erythrocythemia increased hypoxia tolerance during physical exercise.
Cyclooxygenase metabolites in human lung anaphylaxis: airway vs. parenchyma
Authors: Schulman E. S. , Adkinson N. F. , Newball H. H.
Published: December 2017

We studied the generation of arachidonic acid cyclooxygenase metabolites (AACMs) during in vitro anaphylaxis of passively sensitized human lung parenchymal and airway fragments. Prostaglandins E, F2 alpha, D2, 6-keto-prostaglandin F1 alpha, and thromboxane B2 (PGE, PGF2 alpha, PGD2, 6-keto-PGF1 alpha, TXB2, respectively) were assayed by radioimmunoassay. Results with airway tissue were compared with subpleural parenchymal fragments from the same lungs similarly challenged. Spontaneous generation of prostacyclin (PGI2), as measured by its stable metabolite 6-keto-PGF1 alpha, exceeded by two- to threefold other spontaneous AACM release in both bronchial and parenchymal fragments. In airway antigen produced variable AACM responses, but in general the rank order was 6-keto-PGF1 alpha greater than PGE congruent to PGF2 alpha greater than PGD2 greater than TXB2. The rank for antigen-induced AACM release from parenchyma was 6-keto-PGF1 alpha congruent to PGD2 much greater than PGF2 alpha greater than TXB2 congruent to PGE. In airway, as in parenchyma, very little AACM production during anaphylaxis can be attributed to smooth muscle contraction per se. Histamine released from bronchi (0.67 +/- 0.30 micrograms/g lung) was significantly less than from parenchyma (3.7 +/- 0.70 micrograms/g) despite comparable histamine content. At comparable levels of histamine release, the parenchyma produced greater quantities than bronchi of all AACMs except PGE. The comparatively limited bronchial capacity to generate PGF2 alpha, PGD2, TXB2, and histamine (airway constrictors) along with predominant generation of PGI2 and PGE (airway relaxants) may help preserve airway patency.
Augmentation of ventilatory response to asphyxia by prochlorperazine in humans
Authors: Olson L. G. , Hensley M. J. , Saunders N. A.
Published: December 2017

The effect of the dopamine-receptor blocking agent prochlorperazine on the ventilatory response to hypercapnic hypoxia was studied in six healthy adults. Repeated episodes of transient hypoxia were induced at the mixed venous PCO2 level by a nonrebreathing technique in five males and one female before and after an intravenous bolus injection of prochlorperazine mesylate (12.5 mg = 10 mg base). The ventilatory response to CO2 was also studied before and after drug administration. Prochlorperazine produced a modest (15%) increase in resting ventilation (P less than 0.05) but a marked increase in the ventilatory response to asphyxia such that the group mean response was double the control value [2.0 +/- 0.7 vs. 4.2 +/- 1.5 l . min-1 . % arterial O2 saturation (%SaO2); P less than 0.001]. Two-thirds of this change in ventilatory response was due to an increase in frequency response to hypoxia (0.34 +/- 0.20 vs. 0.81 +/- 0.52 breaths . min-1 . %SaO2; P less than 0.001). The position of the ventilatory response line, as judged by the computed ventilation at 95% SaO2, was increased by prochlorperazine (22.2 +/- 9.6 vs. 35.9 +/- 10.9 l . min-1; P less than 0.01) due to an increase in both tidal volume (P less than 0.05) and frequency of breathing (P less than 0.0125). The ventilatory response to CO2 was unchanged by drug injection. In separate experiments prochlorperazine was shown to 1) increase the ventilatory response to steady-state eucapnic hypoxia (P less than 0.01) demonstrating that the drug effect was not dependent on either the presence of hypercapnia or rapidly changing states of arterial oxygenation; and 2) reverse the depressant effect of intravenously infused dopamine hydrochloride (5 micrograms . kg-1 . min-1) on the ventilatory response to transient asphyxia (P less than 0.01). We conclude that prochlorperazine augments hypoxic responsiveness in humans. The mechanism may be blockade of dopaminergic receptors that modulate carotid body discharge.
Effect of aerosolized histamine on occlusion pressure and ventilation in humans
Authors: Millman R. P. , Silage D. A. , Peterson D. D. , Pack A. I.
Published: December 2017

To define further the mechanism by which inspiratory neural activity is increased in asthma, we studied the effect of aerosolized histamine on occlusion pressure (P100) and ventilation in conscious humans while end-tidal CO2 partial pressure was maintained at a constant, slightly hypercapnic level. The dose of histamine we employed varied from subject to subject but was such that it produced a 70% reduction in specific airway conductance in each subject. In 9 of the 13 subjects tested, inhaled histamine significantly increased P100. This increase was not due to changes in functional residual capacity, which was not affected by aerosolized histamine. Inhalation of isoproterenol abolished the effects of histamine on specific airway conductance and P100. Anesthesia of the airways by lidocaine eliminated the effect of histamine on P100 but did not alter the magnitude of the change in specific airway conductance produced by histamine. We conclude that the increase in occlusion pressure seen after the inhalation of histamine in humans depends on both contraction of bronchial smooth muscle and stimulation of airway receptors.
Problems with plethysmographic estimation of lung volume in infants and young children
Authors: Helms P.
Published: December 2017

In 57 infants and very young children, less than 2 yr of age and with a variety of cardiopulmonary illnesses, problems were encountered in the estimation of lung volume with the plethysmographic technique. In 19 subjects calculated thoracic gas volume (TGV) was found to be consistently larger when airway occlusions were performed at low lung volumes than when performed at higher lung volumes. In 13 infants, changes in intraesophageal pressure (Pes) during airway occlusions were found to be larger than simultaneous changes in mouth pressure. In 25 subjects in whom none of the above changes were observed, total pulmonary resistance (TPR) and airway resistance (Raw) did not differ significantly [mean TPR, 50.1 +/- 27.5 cmH2O X l-1; mean Raw, 48.1 +/- 26.5 (P greater than 0.5)]. In the 13 subjects in whom the delta Pes-to-delta Pm occlusion ratio exceeded 1.05, closest agreement with specific resistance (sRaw) and TPR derived lung volume was found when TGV was calculated with delta Pes rather than mouth pressure change (delta Pm). A similar close agreement with the sRaw TPR derived volume was obtained when TGV was calculated during airway occlusions at the higher lung volume. Two separate lung models are proposed to explain these observations, one with a segmental airway closure and the other with more a generalized airway closure. If plethysmographic techniques are to be used in these young subjects for the estimation of lung volume and airway resistance, possible errors may be reduced by performing airway occlusions at lung volumes above functional residual capacity and noting the delta Pes-to-delta Pm ratio obtained during the occlusion.
Regulation of glycogenolysis in human muscle at rest and during exercise
Authors: Chasiotis D. , Sahlin K. , Hultman E.
Published: December 2017

The regulation of glycogenolysis in human muscle during isometric and dynamic exercise has been investigated. Total glycogen phosphorylase and synthase activities were unchanged during exercise. The fraction of phosphorylase in the alpha form at rest was estimated to be 20%, but the data indicate that the in vivo activity was low and critically dependent on the concentration of inorganic phosphate (Pi) in the muscle. Phosphorylase alpha increased initially 2.4-fold during isometric contraction and 1.6-fold during maximal bicycle exercise but reverted to or below the resting value at fatigue/exhaustion. At rest synthase I was 1713;48% of the total activity but decreased during exercise to about half of this value. The reciprocal changes in phosphorylase and synthase correlate with the enhanced rate of glycogenolysis during exercise. Michaelis constant (Km) for Pi was 27 mmol . l-1 for phosphorylase alpha and 7 mmol . l-1 for alpha + b. From consideration of the changes in Pi during exercise (to 20–30 mmol . l–1) it was concluded that Pi is one of the main factors determining phosphorylase activity and provides a link between phosphocreatine breakdown and glycogen utilization in muscle.
Evaluation of a method for estimating cardiac output from a single breath in humans
Authors: Chen H. , Silverton N. P. , Hainsworth R.
Published: December 2017

We have modified the single-breath method of Kim et al. (J. Appl. Physiol. 21: 1338–1344, 1966) for estimating cardiac output and arterial and mixed venous carbon dioxide tensions (PCO2). We assessed this using 30 normal subjects and 23 cardiac patients. The procedure was performed satisfactorily in all but two patients. The random errors, from 60 pairs of estimates of cardiac output in normal subjects and 50 pairs in patients, were +/- 12.8 and +/- 19.6% (95% tolerance limits; i.e., coefficient of variation multiplied by 2 for n greater than 50). The systematic error was assessed in 15 patients from comparisons with results obtained by the direct Fick method. There was no significant difference except in two patients with large intracardiac shunts. Mean values of cardiac output by single-breath and direct Fick estimates were 3.80 and 3.83 l/min. Arterial and mixed venous PCO2 were estimated by the single-breath method with random errors of +/- 1.5 and +/- 1.4 Torr, respectively, and no significant systematic errors. We conclude that our modification of the single-breath method is reliable in humans at rest, although the procedures for delivering the breath and processing the data are of critical importance.
Maximal cardiac function in sedentary normal men and women: comparison of age-related changes
Authors: Hossack K. F. , Bruce R. A.
Published: December 2017

The normal range of maximal values for oxygen consumption, heart rate, cardiac index, and stroke index during treadmill exercise testing are presented for 98 men and 104 women for ages 20–75 yr. These variables decrease with age in both sexes, but men show a significantly greater reduction than women with respect to oxygen consumption (P = 0.05), heart rate (P less than 0.02), and cardiac index (P less than 0.02). Comparison of the normal ranges of oxygen consumption, cardiac index, and stroke index indicated that men have significantly higher values than women (P less than 0.001). The normal range of heart rate was higher in younger men than women, but because of a more rapid decline with age in men, the older women had higher heart rates than the older men. Invasive measurements of cardiac index in 12 normal men and 11 normal women were within the defined normal range. These measurements showed that there was a greater increase in stroke index from supine rest to maximal upright exercise in men compared with the increase in women (means +/- SD, 12 +/- 9 m/m2 vs. 2 +/- 7 ml/m2, P less than 0.01).
Lung expansion and survival in rabbit neonates treated with surfactant extract
Authors: Metcalfe I. L. , Pototschnik R. , Burgoyne R. , Enhorning G.
Published: December 2017

Preterm rabbit fetuses, delivered on the 27th day of gestation, were studied following upper airway instillation with either natural surfactant (NSA) obtained from the lavage of adult rabbit lungs or with a protein-free suspension of lipids extracted from lung wash (ESA). First, lung compliance was studied postmortem. The administration of 25 microliters of either preparation resulted in greater hysteresis (P less than 0.05) than was observed in control fetuses receiving no surfactant material. Increasing the phospholipid concentration stepwise from 10 to 50 mg/ml improved airway expansion and stability. No further improvement was encountered with concentrations greater than 50 mg/ml. There was no significant difference in compliance response between NSA and ESA. Morphometry of the lungs also indicated that the two preparations had an equal effect on compliance. Second, it was determined how neonatal survival was affected by a pharyngeal deposition, prior to the first breath, of 50 microliters NSA or ESA. Both treatment groups demonstrated improved survival (P less than 0.001) when compared with controls receiving no pharyngeal deposition. These findings offer further support to the concept that protein is not required for the efficacy of a surfactant supplementation. The equivalence of the two preparations suggests that a sterile suspension of a protein-free surfactant extract could be used to prevent or treat respiratory distress in preterm neonates.
Control of ventilation in climbers to extreme altitude
Authors: Schoene R. B.
Published: December 2017

Blunted chemosensitivity has been found in successful endurance athletes and some high-altitude natives. This characteristic, however, may not be beneficial to climbers at extreme altitude, where a vigorous ventilatory response to hypoxia may be of value in enhancing alveolar and arterial oxygenation. We studied 14 climbers who had climbed to 7,470 m or higher, 10 age-matched controls, and 10 outstanding middle- and long-distance runners. The ventilatory response to progressive hypoxia was determined at a constant, normal end-tidal Pco2 over 8–12 min and to CO2 by rebreathing a 7% CO2 hyperoxic mixture (Read technique). The hypoxic response parameter of Weil, A was used to determine the hypoxic responses and S (delta VE/ delta PACO2) the hypercapnic response. Climbers had A values significantly higher than the runners (means +/- SE: 158.9 +/- 29.9 vs. 49.3 +/- 7.1, P less than 0.001) but not significantly higher than the controls (109.9 +/- 21.0). delta VE/ delta PACO2 of climbers was higher (3.0 +/- 0.4) than both controls (2.2 +/- 0.2, P less than 0.025) and runners (1.4 +/- 0.2, P less than 0.0005). These data suggest that successful climbers to extreme altitude may be selected by virtue of their vigorous respiratory responses to hypoxia to maintain adequate oxygenation in the presence of extreme environmental hypoxia.
Localization of carbonic anhydrase on pulmonary artery endothelial cells in culture
Authors: Ryan U. S. , Whitney P. L. , Ryan J. W.
Published: December 2017

Bovine pulmonary artery endothelial cells in culture possess carbonic anhydrase activity and immunoreactivity. The intact cells and cell homogenates lower the pH of 25 mM triethanolamine sulfate buffer saturated with CO2 (starting pH 8.1). The intact cells are more reactive than the cell homogenates, and the enzymic activity is enriched in association with the plasma membrane fraction. Specific immunofluorescence is obtained when the cells are incubated with rabbit antibovine erythrocyte carbonic anhydrase B and then with goat antirabbit immunoglobulin G coupled to fluorescein. At the level of electron microscopy, antibodies to carbonic anhydrase B are reactive with sites along the plasma membrane and associated caveolae. Multivesicular bodies are the only intracellular sites labeled and appear to correspond to the globular sites of intracellular immunofluorescence. Cells maintained and propagated in culture in the absence of an exogenous source of carbonic anhydrase nonetheless possess carbonic anhydrase activity, suggesting that the cells are capable of synthesizing the enzyme. Taken together, our results indicate that pulmonary artery endothelial cells possess carbonic anhydrase situated so that the enzyme could readily catalyze the dehydration of plasma HCO-3 to facilitate CO2 excretion and participate in the regulation of blood pH as central venous blood is converted into systemic arterial blood.
Daily in vivo neuromuscular stimulation effects on immobilized rat hindlimb muscles
Authors: Gardiner P. F. , Lapointe M. A.
Published: December 2017

The purpose of the investigation was to determine the effects of a daily regimen of near-maximal contractions, produced via in vivo electrical stimulation of peripheral nerve, on functional and histochemical properties of rat hindlimb muscles immobilized for 28 days in a plaster cast. Rats had knee and ankle joints of one hindlimb immobilized; then while anesthetized, half of the group was subjected to a daily regimen of 480 semifused tetanic contractions (50 Hz) via fine-wire electrodes chronically implanted around the sciatic nerve. Immobilization caused significant decreases in soleus and gastrocnemius muscle weights, fiber cross-sectional areas, and twitch and tetanic strength measured in situ. In addition, immobilized soleus muscles had faster time to peak tension (TPT) and higher proportions of fast-twitch fibers, whereas immobilized gastrocnemius muscles demonstrated faster half-relaxation times (RT1/2) and total twitch durations (TPT plus RT1/2). The only significant effects of the imposed contractions were evident in the gastrocnemius in which stimulation prevented the shortening of RT1/2 and total twitch duration and resulted in significantly higher relative tensions at 50 Hz and higher fatigue resistance. Muscle activity of this type imposed on immobilized muscle is ineffective in attenuating atrophy but can, in fast muscle such as gastrocnemius, prevent changes in twitch characteristics resulting from immobilization, as well as augment contractile responses during semifused and fatiguing contractions.
Bronchomotor responses of isolated sheep airways to electrical field stimulation
Authors: Sheller J. R. , Brigham K. L.
Published: December 2017

To determine the functional innervation of sheep airway smooth muscle, we measured the isometric tension developed by sheep tracheal segments, bronchial rings, and lung parenchymal strips in response to electrical field stimulation (ES) in tissue chambers. The contractions caused by ES were abolished in trachea and bronchi by atropine 10(-6) M or tetrodotoxin 1.6 X 10(-6) M. The small contractions evoked in lung parenchymal strips were not affected by tetrodotoxin. Electrical stimulation in the presence of atropine 10(-6) M and phentolamine 10(-6) M caused a frequency-dependent reduction in serotonin-induced tension in tracheal segments and bronchial rings. Electrical stimulation had little or no effect on the tension evoked in lung parenchymal strips by acetylcholine 10(-5) M or to histamine 10(-6) M. Propranolol 10(-6) M or guanethidine 10(-5) M caused a shift to the right in the frequency-response curve of trachea and bronchi. These findings suggest the presence of cholinergic excitatory and adrenergic inhibitory innervation in larger sheep airways. A concomitant nonadrenergic inhibitory system may be present. The terminal bronchioles present in lung parenchymal strips do not appear to have an effective bronchomotor innervation.
Changes in EMG power spectrum (high-to-low ratio) with force fatigue in humans
Authors: Moxham J. , Edwards R. H. , Aubier M. , De Troyer A. , Farkas G. , Macklem P. T. , Roussos C.
Published: December 2017

During and following high-load fatiguing voluntary contractions, the force response of skeletal muscle to electrical stimulation is altered so that the frequency-force curve is moved to the right. Fatiguing contractions also result in a shift to the left of the electromyographic (EMG) power spectrum. In the quadriceps muscle and the diaphragm of normal subjects the change in the force response to electrical stimulation has been correlated with the EMG changes. After repeated submaximal contractions in the quadriceps and diaphragm, the forces produced by electrical stimulation at low frequencies were reduced, indicating low-frequency fatigue. This type of fatigue persisted for several hours but did not result in any change in the EMG high-to-low ratio. Low-frequency fatigue is probably an important aspect of the failure of skeletal muscle to generate adequate force, and the EMG high-to-low ratio may not recognize this type of fatigue.
Mitochondrial function in the presence of myoglobin
Authors: Cole R. P. , Sukanek P. C. , Wittenberg J. B. , Wittenberg B. A.
Published: December 2017

The effect of myoglobin on oxygen consumption and ATP production by isolated rat skeletal muscle mitochondria was studied under steady-state conditions of oxygen supply. A method is presented for the determination of steady-state oxygen consumption in the presence of oxygen-binding proteins. Oxygen consumed in suspensions of mitochondria was replenished continuously by transfer from a flowing gas phase. Liquid-phase oxygen pressure was measured with an oxygen electrode; the gas-phase oxygen concentration was held constant at a series of fixed values. Oxygen consumption was determined from the characteristic response time of the system and the difference in the steady-state gas- and liquid-phase oxygen concentrations. ATP production was determined from the generation of glucose 6-phosphate in the presence of hexokinase. During steady-state mitochondrial oxygen consumption, the oxygen pressure in the liquid phase is enhanced when myoglobin is present. Functional myoglobin present in the solution had no effect on the relation of mitochondrial respiration and ATP production to liquid-phase oxygen pressure. Myoglobin functions in this system to enhance the flux of oxygen into the myoglobin-containing phase. Myoglobin may function in a similar fashion in muscle by increasing oxygen flux into myocytes.
How does increased cardiac output increase shunt in pulmonary edema?
Authors: Breen P. H. , Schumacker P. T. , Hedenstierna G. , Ali J. , Wagner P. D. , Wood L. D.
Published: December 2017

In pulmonary edema, the relationship between cardiac output (QT) and shunt (QS/QT) may be due to a diffusion barrier for O2 transfer (incomplete alveolar-capillary equilibration) or to redistribution of increased pulmonary blood flow toward edematous units. We compared transfer of O2 and multiple inert gases in the left (LLL) and right (RLL) lower lobes and in the whole lungs of eight dogs having oleic acid edema in LLL. When mean QT was increased from 3.0 to 5.5 l X min-1 during O2 ventilation, relative perfusion of LLL did not increase but QS/QT increased because LLL shunt increased from 56 to 78%. We conclude that increased pulmonary blood flow is not redistributed toward edematous regions, but we cannot exclude such redistribution within LLL and other slightly edematous lobes. In LLL, inert gas shunt and O2 shunt were not systematically different during O2 ventilation, and lobar venous PO2 measured during air ventilation was not different from that predicted by inert gas transfer. We conclude that diffusion limitation for O2 does not contribute to QS/QT or to the increase in QS/QT when QT increases. Conceivably, increased QT increased QS/QT by increasing edema or hematocrit in edematous regions.
Effects on heat tolerance of physical training in water and on land
Authors: Avellini B. A. , Shapiro Y. , Fortney S. M. , Wenger C. B. , Pandolf K. B.
Published: December 2017

A 4-wk training program was undertaken by 15 untrained non-heat-acclimated males who were divided into three groups matched on maximal aerobic capacity (VO2max) and trained either in water or on land to determine how physical training (PT) in these different media affects heat tolerance. Subjects trained on a cycle ergometer for 1 h/day, 5 days/wk at 75% VO2max, with the exercise intensity progressively increased to maintain a constant training stimulus. Group I exercised on land, whereas groups II and III exercised while immersed to the neck in water of either 32 degrees C (II) or 20 degrees C (III). Daily exercise increased core temperature (Tc) in groups I and II but not in group III. Training elicited similar increases (approximately 15%) in VO2max in the three groups. Before and after PT, all subjects exercised at approximately 30% VO2max for 3 h at 49 degrees C, 20% rh. Compared with before training, groups I and II showed a decrease in final Tc and heart rate (HR) in the posttraining heat exposure. Sweat rate increased 25% in group II but remained the same in group I. Group III demonstrated a decrease in final HR, but final Tc was higher than before training. Sweat rate did not increase in group III and was lower than the other groups. It was concluded that PT can improve the cardiovascular response to dry heat without affecting thermoregulatory capacity. PT appears to enhance heat tolerance only if Tc is permitted to rise during exercise, thus stimulating the temperature-regulating center for heat dissipation.
Effect of increased oxygen affinity and anemia on cardiac output and its distribution
Authors: Woodson R. D. , Auerbach S.
Published: December 2017

Effect of increased blood O2 affinity on cardiac output and its distribution was studied in conscious sedated rats by the microsphere-reference sample method. After a preliminary measurement of cardiac output and its distribution, rats were exchange transfused with normal blood or low-P50 (PO2 at which hemoglobin is half-saturated with O2) blood; other groups were made anemic with and without a simultaneous reduction in P50. Reduction in P50 from 38 to 17 Torr did not change cardiac output, pulse, or blood pressure but caused, after allowance for changes in controls, a 102% increase in coronary blood flow and an 88% increase in cerebral blood flow. Anemia (hematocrit = 22%) produced similar changes in coronary and cerebral flow. When anemia was combined with a 12-Torr reduction in P50, coronary and cerebral flow increased by 297 and 209%, respectively. These increases in coronary and cerebral flow were not attributable to increased cardiac work or hypercapnia. It is concluded that a left shift of the O2 dissociation curve induces increased blood flow to brain and heart, probably in compensation for decreased tissue O2 pressure.
Effect of O2 affinity on arterial PO2 in animals with central vascular shunts
Authors: Wood S. C.
Published: December 2017

Central vascular or intracardiac shunts result in venous admixture and reduced saturation of systemic arterial blood. This is pronounced in most species of amphibians and reptiles and may occur as congenital defects in homeotherms. A two-compartment model is useful to analyze the effects of shunt on O2 transport. The PO2 of a mixture of pulmonary (ideal) and mixed venous (shunt) blood will be a function of the resulting O2 saturation, analogous to the principle of the “mixing method” in vitro. Furthermore, for a given saturation, the PO2 of systemic arterial blood (PaO2) should be inversely related to the O2 affinity of the mixed blood. The present study tested this two-compartment model of shunt in animals with normally occurring right-to-left shunts (amphibians and reptiles) and with dogs having artificial shunts. The O2 dissociation curves (ODC) of the blood were manipulated by varying body temperature and blood pH. For any level of saturation of systemic arterial blood, the PaO2 was found to increase with factors that shifted the ODC to the right. This experimental support of mathematical models of shunting and PaO2 suggests that animals with intracardiac or central vascular shunts are benefited by low-O2-affinity blood, a condition that is common in amphibians and reptiles. For an individual ectothermic vertebrate, an increase in O2 demand due to increased body temperature would, because of decreased O2 affinity, be accompanied and perhaps facilitated by an increase in PaO2 if saturation remained constant.
Acid-base stress and central chemical control of ventilation in turtles
Authors: Hitzig B. M. , Nattie E. E.
Published: December 2017

Central chemical control of ventilation in turtles, Chrysemys (Pseudemys) scripta, has been characterized by alterations in breathing frequency (f). To assess the effects of acid-base stress on the central ventilatory response, three groups of animals were subjected to 2 h of anoxia (98% N2–2% CO2), 2 h of hypercapnia (8% CO2 in air), or 2 h of anoxia plus hypercapnia (92% N2–8% CO2). Ventilatory responses were measured continuously, and arterial blood and cerebrospinal fluid (CSF) acid-base variables were determined after 2 h. Results show that central ventilatory responses (f) were significantly elevated in CSF acidosis caused by CO2 over those caused by the accumulation of CSF fixed acid alone (anoxia). The increases in f did not correlate with decreases in estimated CSF pH, since it was much lower in anoxia (7.19) than in hypercapnia (7.37). Our results strongly suggest that the central nervous system acidosis caused by anoxia produces centrally mediated ventilatory change in a fundamentally different way from hypercapnia.
Regulatory processes of metabolic and respiratory acid-base disturbances in embryos
Authors: Tazawa H.
Published: December 2017

First, preliminary experiments were designed in the 16-day-old individual chick embryo to elucidate the effect of electrolyte infusion and blood samplings on hemodilution, which might influence the acid-base balance. Three kinds of hemodilution were observed: 1) hemodilution caused by four repetitive samplings, which had no influence on acid-base balance; 2) hypervolumic hemodilution caused by infusion of solution whose volume equaled about 5–6% of total blood volume, which induced dilution acidosis; and 3) hypertonic hemodilution caused by hypertonic electrolyte infusion, which also induced dilution acidosis. The embryo recovered from the hypertonic dilution acidosis in 6 h after infusion, but it did not recover from hypervolumic acidosis. Second, the time course of changes in metabolic and respiratory acid-base disturbances was studied in the individual embryo. Metabolic acid-base disturbances made by hypertonic NaHCO3 infusion were restored to control state in 6 h. Respiratory acid-base disturbances were also regulated in terms of changes in plasma[HCO-3] and pH. The renal function and redistribution of HCO-3 may in part be responsible for the regulation.
Variability of fiber type distributions within human muscles
Authors: Elder G. C. , Bradbury K. , Roberts R.
Published: December 2017

The variability of fiber type distributions between different regions of the same human muscle is believed to be small, based on the sampling of between two and four sites. The objective of the present investigation was to determine the variability of slow-twitch (ST) and fast-twitch (FT) fiber distributions using a more extensive sampling technique than those previously employed. The soleus, biceps, triceps, and vastus lateralis muscles were excised from each of four young men who had died suddenly. Between 13 and 17 sites were sampled from each of the muscles; 3 transverse areas were then examined within each sample. Fiber type distributions were determined from photographs of sections stained for myofibrillar adenosine triphosphatase at pH 10.3, 10.0, or 4.3. The numbers of fibers counted in the four muscles ranged between a mean of 13,660 and a mean of 21,601. The variability in fiber type distributions observed between sites and areas within a site were statistically greater (P less than 0.01) than could be expected from muscles whose fiber type distributions are equally distributed throughout the muscle. It was concluded that sampling between 3 and 5 sites in the different muscles was necessary to reduce the between-site standard deviation to 5%.
A Starling resistor regulates cerebral venous outflow in dogs
Authors: Luce J. M. , Huseby J. S. , Kirk W. , Butler J.
Published: December 2017

This investigation was undertaken to determine whether a Starling resistor or venous waterfall effect exists between the sagittal sinus and the cerebral veins such that increases in sagittal sinus pressure (Pss) do not abolish cerebral venous outflow and to examine two possible contributions of extracranial venous valves in regulating outflow. Anesthetized dogs were subjected to positive end-expiratory pressure (PEEP) before and after intracranial pressure (Pic) was elevated by inflation of an epidural balloon. PEEP raised Pss equally in all animals, but Pic and cerebral venous pressure (Pcv) increased less in the presence of intracranial hypertension. When Pss was low, passage of a catheter in the cerebral vein in and out of the sagittal sinus demonstrated an abrupt drop in pressure as the sinus was entered. When Pss was raised and lowered independently of superior vena caval pressure (Psvc) the changes in Pic and Pcv were less when Pss was decreased than when it was increased. Sustained increases and decreases in Psvc caused increases and decreases in Pcv, Pic, Pss, and external jugular venous pressure (Pejv) regardless of whether external jugular venous valves were present or absent. We conclude that a Starling resistor between the sagittal sinus and the cerebral veins regulates cerebral venous outflow when Pss is increased by PEEP and other maneuvers that raise Psvc. The waterfall maintains Pcv and Pic at normal levels when Psvc and Pss are reduced. Extracranial venous valves are not essential to this mechanism.
Temperature and adrenocortical responses in rhesus monkeys exposed to microwaves
Authors: Lotz W. G. , Podgorski R. P.
Published: December 2017

To determine if the endocrine response to microwave exposure was similar in a primate to that reported for other animals, rectal temperature and plasma levels of cortisol, thyroxine (T4), and growth hormone (GH) were measured in rhesus monkeys exposed to 1.29 GHz microwave radiation. Exposures were carried out under far-field conditions with the monkey restrained in a chair. Incident power densities of 0, 20, 28, and 38 mW/cm2 were used, with corresponding specific absorption rates of 0, 2.1, 3.0, and 4.1 W/kg. Blood samples were taken hourly via an indwelling jugular venous catheter over a 24-h period before, during, and after an 8-h exposure. Rectal temperature increased an average of 0.5, 0.7, and 1.7 degrees C for the three intensities used. No changes in T1 or GH were observed. Cortisol levels were increased during exposure to 38 mW/cm2. It was concluded that the temperature and adrenocortical responses to microwave exposure of the rhesus monkey are similar to the corresponding responses of other animals.
Autonomic contribution to heart rate recovery from exercise in humans
Authors: Savin W. M. , Davidson D. M. , Haskell W. L.
Published: December 2017

To assess the contribution of the autonomic nervous system to heart rate recovery following exertion, heart rate was observed after peak treadmill exercise in six men following parasympathetic blockade (PB) with atropine sulfate (0.03 mg/kg), sympathetic blockade (SB) with propranolol hydrochloride (0.20 mg/kg), double blockade (DB) with both drugs, and no drugs (ND). Least-squares analysis of each subject's heart rate (HR) as an exponential function of recovery time (t) was computed for each treatment giving an equation of the form HR = aebt. HRs at rest, peak exercise, and 10 min of recovery, the coefficients a and b, and the least-squares correlation coefficient (r) were compared among treatments by nonparametric analysis of variance and rank-sum multiple comparisons. HR recovered in an exponential manner after dynamic exercise in each subject with each of the treatment modes (P less than 0.01 for each r, mean across all treatments r = 0.94). Coefficients a and b differed the most between PB and SB. At the cessation of exercise the decreases in venous return and the systemic need for cardiac output are accompanied by an exponential HR decline. The exponential character of the cardiodeceleration seen after peak exercise appears to be an intrinsic property of the circulation because it occurred under each experimental condition.
Intravenous versus inhaled atropine for inhibiting bronchoconstrictor responses in dogs
Authors: Holtzman M. J. , McNamara M. P. , Sheppard D. , Fabbri L. M. , Hahn H. L. , Graf P. D. , Nadel J. A.
Published: December 2017

We studied whether the muscarinic antagonist, atropine, given intravenously or by inhalation, inhibits the bronchoconstrictor responses to inhaled acetylcholine and to acetylcholine released by electrical stimulation of the vagus nerves to the same degree. We assessed bronchoconstrictor responses in anesthetized dogs by determining the increase in total pulmonary resistance before and after increasing doses of atropine and then constructing inhibition dose-response curves. Before atropine the responses to the two stimuli were equal in magnitude. After intravenous atropine (initial dose 0.12 micrograms/kg, total dose 16 micrograms/kg) both responses were progressively inhibited to a similar degree. By contrast, after inhaled atropine (initial dose 0.02 micrograms/kg, total dose 2.4 micrograms/kg) the response to acetylcholine inhalation was inhibited to a much greater degree than the response to vagal stimulation. Thus, in studies designed to inhibit bronchoconstriction due to an inhaled muscarinic agonist to the same degree as bronchoconstriction due to a vagal reflex, atropine might better be given intravenously than by inhalation.
Effects of hypercapnia, hypoxia, and rebreathing on circulatory response to apnea
Authors: Lin Y. C. , Shida K. K. , Hong S. K.
Published: December 2017

Cardiovascular responses to cessation of respiration and to progressive hypoxia and hypercapnia were investigated noninvasively in eight male volunteers. A total of five 90-s breath holds (BH) with face immersion were performed by each subject. A continuous BH (BH-1) eliminated the circulatory effects of respiratory movements, BH with air (BH-3) or with O2 (BH-5) with rebreathing at 15-s intervals through a CO2 scrubber reduced the effect of hypercapnia, and BH with air (BH-2) or with O2 (BH-4) with rebreathing at 15-s intervals bypassing the CO2 scrubber produced hypercapnia with or without concomitant hypoxia. Mean arterial blood pressure rose continuously in BH-1 and BH-2 and to a much lesser degree in other BHs. Vasoconstriction was evident within 30 s of BH. Determined by impedance cardiograph, stroke volume (SV) rose by 33%, which was balanced out by a 30% reduction in heart rate (HR) from the pre-BH values, at the end of a continuous BH. A transient depression of cardiac output (CO) was observed at 30 and 60 s of BH-1. CO values were maintained at pre-BH levels throughout the BHs where progressive hypercapnia occurred (BH-2 and BH-4) but were depressed to a similar degree as BH-1 when hypercapnia was prevented (BH-3 and BH-5). Alveolar CO2 levels were found to be correlated linearly and positively with SV, HR, and CO. No such relationship existed between alveolar O2 levels and these hemodynamic parameters. Thus rebreathing and hypercapnia during BH prevented CO from falling during BH. It is reasoned that hypercapnia and consequent acidosis, through enhanced sympathoadrenal release of catecholamines, was responsible for the compensatory SV response.
Ascorbate uptake by isolated rat alveolar macrophages and type II cells
Authors: Castranova V. , Wright J. R. , Colby H. D. , Miles P. R.
Published: December 2017

Studies were conducted to measure intracellular ascorbate content and to characterize ascorbate uptake in three fractions of isolated rat pneumocytes (i.e., alveolar macrophages, alveolar type II epithelial cells, and another fraction of small pneumocytes that contains neither macrophages nor type II cells). When cells are incubated in medium containing 0.1 mM ascorbate (i.e., the concentration normally found in plasma), intracellular ascorbate concentrations are 3.2 mM in alveolar macrophages and type II cells and 0.9 mM in other lung cells; ascorbate influx is 1.5 nmol . 10(7) cells-1 . h-1 for alveolar macrophages, 0.24 nmol . 10(7) cells-1 . h-1 for type II cells, and very slow in other pneumocytes. Ascorbate influx displays saturation kinetics in both alveolar macrophages (K1/2 = 2 mM; Vmax = 32.2 nmol . 10(7) cells-1 . h-1) and type II cells (K1/2 = 5 mM; Vmax = 14.2 nmol . 10(7) cells-1 . h-1). After correction for differences in the membrane surface areas of these two types of lung cells, the rates for maximum ascorbate influx (Vmax) are similar in alveolar macrophages and type II cells. In addition, ascorbate uptake by alveolar macrophages and type II cells is dependent on metabolic activity and extracellular sodium. In contrast, ascorbate uptake in other lung cells does not exhibit saturation kinetics and is not dependent on metabolism or sodium. Thus alveolar macrophages and type II cells possess an energy-dependent cotransport system for ascorbate and sodium influx. The high ascorbate content and the existence of a specialized transport mechanism for ascorbate uptake may explain the relative resistance of alveolar macrophages and type II cells to oxidant injury.