bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential metabolic responses of periarticular ligaments and tendon to joint immobilization
Authors: Harwood F. L. , Amiel D.
Published: December 2017

Parameters of collagen metabolic behavior were analyzed in the periarticular connective tissues, i.e., medial collateral ligament (MCL), anterior cruciate ligament (ACL), and patellar tendon (PT), of control and immobilized rabbit knees. Two periods of immobilization were studied: 9 and 12 wk. Collagen turnover and collagen cross-links were quantitatively assessed in the three tissues. The results showed that after 9 wk both synthesis and degradation were significantly increased in the MCL and ACL, whereas the PT showed lesser effects. After 12 wk all three tissues experienced significant losses of collagen mass, which resulted in tissue atrophy. The concentrations of the reducible collagen cross-links dihydroxylysinonorleucine and hydroxylysinonorleucine in the immobilized MCL and ACL were greater than their respective controls, indicating an increase in collagen synthesis, whereas concentrations of the nonreducible cross-link hydroxypyridinoline were observed to be decreased in these tissues. Of the reducible cross-links in the PT, only hydroxylysinonorleucine was found to be increased over control, whereas hydroxypyridinoline was slightly less concentrated. These results taken together have demonstrated that the ligamentous tissues are more susceptible to the effects of stress deprivation secondary to joint immobilization than the PT, and, in particular, the ACL of the three tissues studied appears to be most vulnerable.
Kinetics of CO uptake and diffusing capacity in transition from rest to steady-state exercise
Authors: Kinker J. R. , Haffor A. S. , Stephan M. , Clanton T. L.
Published: December 2017

In the transition from rest to steady-state exercise, O2 uptake from the lungs (VO2) depends on the product of pulmonary blood flow and pulmonary arteriovenous O2 content difference. The kinetics of pulmonary blood flow are believed to be somewhat faster than changes in pulmonary arteriovenous O2 content difference. We hypothesized that during CO breathing, the kinetics of CO uptake (VCO) and diffusing capacity for CO (DLCO) should be faster than VO2 because changes in pulmonary arteriovenous CO content difference should be relatively small. Six subjects went abruptly from rest to constant exercise (inspired CO fraction = 0.0005) at 40, 60, and 80% of their peak VO2, measured with an incremental test (VO2peak). At all exercise levels, DLCO and VCO rose faster than VO2 (P less than 0.001), and DLCO rose faster than VCO (P less than 0.001). For example, at 40% VO2peak, the time constant (tau) for DLCO in phase 2 was 19 +/- 5 (SD), 24 +/- 5 s for VCO, and 33 +/- 5 s for VO2. Both VCO and DLCO increased with exercise intensity but to a lesser degree than VO2 at all exercise intensities (P less than 0.001). In addition, no significant rise in DLCO was observed between 60 and 80% VO2peak. We conclude that the kinetics of VCO and DLCO are faster than VO2, suggesting that VCO and DLCO kinetics reflect, to a greater extent, changes in pulmonary blood flow and thus recruitment of alveolar-capillary surface area. However, other factors, such as the time course of ventilation, may also be involved.(ABSTRACT TRUNCATED AT 250 WORDS)
Bronchial vasodilation by histamine in sheep: characterization of receptor subtype
Authors: Parsons G. H. , Villablanca A. C. , Brock J. M. , Howard R. S. , Colbert S. R. , Nichol G. M. , Chung K. F.
Published: December 2017

Histamine has been shown to mediate features of pulmonary allergic reactions including increased tracheobronchial blood flow. To determine whether the increase in blood flow was due to stimulation of H1- or H2-histamine receptors, we gave histamine base (0.1 micrograms/kg iv) or histamine dihydrochloride as an aerosol (10 breaths of 0.5% “low dose” or 5% “high dose”) before and after H1- or H2-receptor antagonists. Blood velocity in the common bronchial branch of the bronchoesophageal artery (Vbr) was continuously measured using a chronically implanted Doppler flow probe. Pretreatment with H2-receptor antagonists cimetidine, ranitidine, or metiamide did not affect the increase in Vbr induced by intravenous histamine [106 +/- 45% (SD)]. Addition of the H1-receptor antagonists diphenhydramine or chlorpheniramine, however, reduced the Vbr response to 16 +/- 22, 21 +/- 28, 23 +/- 23, and 37 +/- 32% of the unblocked responses (P less than 0.05) when intravenous histamine was given at 3, 10, 20, and 30 min, respectively, after the H1 antagonist. At 40, 50, and 60 min the H1-receptor blockade appeared to attenuate, but subsequent continuous infusion of chlorpheniramine (2 mg.kg-1.min-1) then blocked the histamine response for 60 min. Low-dose histamine aerosol did not change mean arterial or pulmonary arterial pressures, cardiac output, or arterial blood gases but increased Vbr transiently from 15.2 +/- 3.4 to 37.6 +/- 8.4 (SE) cm/s. After chlorpheniramine, the Vbr response to histamine, 16.3 +/- 2.2 to 22.6 +/- 3.6 cm/s, was significantly reduced (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Daltroban blocks thromboxane responses in the pulmonary vascular bed of the cat
Authors: Hood J. S. , Nossaman B. D. , Ibrahim I. N. , McMahon T. J. , Babycos C. R. , Kadowitz P. J.
Published: December 2017

The influence of daltroban (BM13.505; SK&F 96148), a thromboxane (Tx) A2-receptor-blocking agent, on responses to the TxA2 mimics U-46619 and U-44069 was investigated in the pulmonary vascular bed of the intact-chest cat under constant-flow conditions. Daltroban (5 mg/kg iv) had no significant effect on mean baseline vascular pressures but significantly decreased responses to the TxA2 mimics without altering responses to prostaglandin (PG) F2 alpha or PGD2 or the PGD2 metabolite 9 alpha, 11 beta-PGF2. Dose-response curves for U-46619 and U-44069 were shifted to the right in a parallel manner, and daltroban had no significant effect on responses to norepinephrine, serotonin, angiotensin II, BAY K 8644, endothelin-(ET) 1, ET-2, or platelet-activating factor (PAF). After administration of daltroban, responses to U-46619 returned to 50% of control in 90 min and responses to the PG and TxA2 precursor arachidonic acid were decreased significantly. These results suggest that daltroban selectively antagonizes TxA2-receptor-mediated responses in a competitive and reversible manner. These data provide support for the hypothesis that discrete TxA2 receptors unrelated to receptors stimulated by PGF2 alpha, PGD2, or 9 alpha, 11 beta-PGF2 are present in the pulmonary vascular bed of the cat. The present data suggest that pulmonary vasoconstrictor responses to PAF and ET peptides are not dependent on activation of TxA2 receptors in the cat.
Effects of moderate hypothermia on O2 consumption at various O2 deliveries in a sheep model
Authors: Sinard J. M. , Vyas D. , Hultquist K. , Harb J. , Bartlett R. H.
Published: December 2017

The effects of modest hypothermia on oxygen consumption (VO2) were studied at various levels of oxygen delivery (DO2) in six sheep. Each animal was placed on cardiopulmonary bypass by extrathoracic cannulations. DO2 was varied by changing blood flow through an extracorporeal circuit. VO2 was measured spirometrically across a membrane lung. VO2 was initially measured at various levels of DO2 at normothermic temperatures (39 degrees C). The animals were then cooled to 33 degrees C. DO2 was varied, and the corresponding VO2's were determined. The data at both temperatures demonstrated the biphasic relationship of VO2 to various levels of DO2. A critical level of DO2 (DO2 crit) was defined to reflect the transition area between the dependent and independent portions of the consumption-delivery curve. The average baseline VO2's on the delivery independent portion of the curve were calculated to be 5.33 and 3.17 ml O2.kg-1.min-1 at 39 and 33 degrees C, respectively (P less than 0.001). The corresponding DO2 crit's were 6.17 and 4.57 ml O2.kg-1.min-1 (P less than 0.05). The oxygen extraction ratios at DO2 crit for each of these temperatures did not differ significantly. We conclude that hypothermia, by lowering baseline VO2, reduces DO2 crit. Hypothermia may therefore reduce or eliminate the anaerobic metabolism and subsequent acidosis that would otherwise occur during normothermia at low levels of DO2.
Exercise training prevents decline in stroke volume during exercise in young healthy subjects
Authors: Spina R. J. , Ogawa T. , Martin W. H. , Coggan A. R. , Holloszy J. O. , Ehsani A. A.
Published: December 2017

Stroke volume (SV) increases above the resting level during exercise and then declines at higher intensities of exercise in sedentary subjects. The purpose of this study was to determine whether an attenuation of the decline in SV at higher exercise intensities contributes to the increase in maximal cardiac output (Qmax) that occurs in response to endurance training. We studied six men and six women, 25 +/- 1 (SE) yr old, before and after 12 wk of endurance training (3 days/wk running for 40 min, 3 days/wk interval training). Cardiac output was measured at rest and during exercise at 50 and 100% of maximal O2 uptake (Vo2max) by the C2H2-rebreathing method. VO2max was increased by 19% (from 2.7 +/- 0.2 to 3.2 +/- 0.3 l/min, P less than 0.001) in response to the training program. Qmax was increased by 12% (from 18.1 +/- 1 to 20.2 +/- 1 l/min, P less than 0.01), SV at maximal exercise was increased by 16% (from 97 +/- 6 to 113 +/- 8 ml/beat, P less than 0.001) and maximal heart rate was decreased by 3% (from 185 +/- 2 to 180 +/- 2 beats/min, P less than 0.01) after training. The calculated arteriovenous O2 content difference at maximal exercise was increased by 7% (14.4 +/- 0.4 to 15.4 +/- 0.4 ml O2/100 ml blood) after training. Before training, SV at VO2max was 9% lower than during exercise at 50% VO2max (P less than 0.05). In contrast, after training, the decline in SV between 50 and 100% VO2max was only 2% (P = NS). Furthermore, SV was significantly higher (P less than 0.01) at 50% VO2max after training than it was before. Left ventricular hypertrophy was evident, as determined by two-dimensional echocardiography at the completion of training. The results indicate that in young healthy subjects the training-induced increase in Qmax is due in part to attenuation of the decrease in SV as exercise intensity is increased.
Spontaneous injury in isolated sheep lungs: role of resident polymorphonuclear leukocytes
Authors: Pearse D. B. , Sylvester J. T.
Published: December 2017

Perfusion of isolated sheep lungs with homologous blood caused pulmonary hypertension and edema that was not altered by depletion of perfusate polymorphonuclear (PMN) leukocytes (D. B. Pearse et al., J. Appl. Physiol. 66: 1287–1296, 1989). The purpose of this study was to evaluate the role of resident PMN leukocytes in this injury. First, we quantified the content and activation of lung PMN leukocytes before and during perfusion of eight isolated sheep lungs with a constant flow (100 ml.kg-1.min-1) of homologous blood. From measurements of myeloperoxidase (MPO) activity, we estimated that the lungs contained 1.2 x 10(10) PMN leukocytes, which explained why the lung PMN leukocyte content, measured by MPO activity and histological techniques, did not increase significantly with perfusion, despite complete sequestration of 2.0 x 10(9) PMN leukocytes from the perfusate. MPO activities in perfusate and lymph supernatants did not increase during perfusion, suggesting that lung PMN leukocytes were not activated. Second, we perfused lungs from 6 mechlorethamine-treated and 6 hydroxyurea-treated sheep with homologous leukopenic blood and compared them with 11 normal lungs perfused similarly. Despite marked reductions in lung PMN leukocyte concentration, there were no differences in pulmonary arterial pressure, lymph flow, or reservoir weight between groups. Extravascular lung water was greater in both groups of leukopenic lungs. These results suggest that resident PMN leukocytes did not contribute to lung injury in this model.
Respiratory and circulatory activities in carotid body-resected humans
Authors: Honda Y.
Published: December 2017

The respiratory and circulatory activities of patients who underwent carotid body resection (CBR) more than two decades ago were reviewed. No significant ventilatory response to continuous hypoxia was observed. However, in response to stimulation of peripheral chemoreceptors, transient hyperventilation occurred before hypoxemic blood arrived at the central nervous system (single-breath test), which indicated the presence of weak peripheral chemosensitivity. Because of this slight residual peripheral chemosensitivity, which was found shortly after the operation and apparently remained more or less unchanged for greater than 20 years, peripheral chemoreceptor activity, which has been reported in other animal species, does not seem to have returned. Delayed hypoxic hyperventilation reported in dogs and cats with CBR was not observed. Hypoxia significantly depressed the ventilatory response to CO2, but the delayed ventilatory depression with time that has been demonstrated in normal subjects did not occur. In our circulatory studies, hypoxia augmented the heart rate and slightly depressed the stroke volume and total peripheral resistance in the systemic circulation but induced no appreciable changes in arterial blood pressure or cardiac output. We used these results to partition the relative contributions to the overall circulatory response of carotid body stimulation, pulmonary inflation, and other modifying influences. From these calculations, it was inferred that the carotid body reflex plays a dominant role in vascular activities whereas the pulmonary inflation reflex dominates in cardiac activities in humans.
Pulmonary hemodynamics in fetal lambs during development at normal and increased oxygen tension
Authors: Morin F. C. , Egan E. A.
Published: December 2017

During the latter third of gestation, the number of resistance vessels in the lungs of the fetal sheep increases by 10-fold even after correction for lung growth. We measured pulmonary arterial pressure and blood flow directly and calculated total pulmonary resistance (pressure divided by flow) in intrauterine fetal lambs at 93–95 days and at 136 days of gestation (term is 145–148 days). In addition, we used a hyperbaric chamber to increase oxygen tension in the fetuses and measured the effect on the pulmonary circulation. When corrected for wet weight of the lungs, pulmonary blood flow did not change with advancing gestation (139 +/- 42 to 103 +/- 45 ml.100 g-1.min-1). Pulmonary arterial pressure increased (42 +/- 5 to 49 +/- 3 mmHg); thus total pulmonary resistance increased with advancing gestation from 0.32 +/- 0.12 to 0.55 +/- 0.21 mmHg.100 g.min.ml-1. If the blood flow is corrected for dry weight of the lungs, neither pulmonary blood flow nor total pulmonary resistance changed with advancing gestation. Increasing oxygen tension increased pulmonary blood flow 10-fold in the more mature fetuses but only 0.2-fold in the less mature fetuses. At the normal low oxygen tension of the fetus, pulmonary blood flow does not increase between these two points of gestation in the fetal lamb despite the increase in vessel density in the lungs. However, during elevated oxygen tension, pulmonary blood flow does increase in proportion to the increase in vessel density.
Respiratory muscle blood flow in exercising dogs after pneumonectomy
Authors: Hsia C. C. , Ramanathan M. , Pean J. L. , Johnson R. L.
Published: December 2017

In three foxhounds after left pneumonectomy, the relationships of ventilatory work and respiratory muscle (RM) blood flow to ventilation (VE) during steady-state exercise were examined. VE was measured using a specially constructed respiratory mask and a pneumotach; work of breathing was measured by the esophageal balloon technique. Blood flow to RM was measured by the radionuclide-labeled microsphere technique. Lung compliance after pneumonectomy was 55% of that before pneumonectomy; compliance of the thorax was unchanged. O2 uptake (VO2) of RM comprised only 5% of total body VO2 at exercise. At rest, inspiratory muscles received 62% and expiratory muscles 38% of the total O2 delivered to the RM (QO2RM). During exercise, inspiratory muscles received 59% and expiratory muscles 41% of total QO2RM. Blood flow per gram of muscle to the costal diaphragm was significantly higher than that to the crural diaphragm. The diaphragm, parasternals, and posterior cricoarytenoids were the most important inspiratory muscles, and internal intercostals and external obliques were the most important expiratory muscles for exercise. Up to a VE of 120 l/min through one lung, QO2RM constituted only a small fraction of total body VO2 during exercise and maximal vasodilation in the diaphragm was never approached.
Immediate diaphragmatic electromyogram responses to imperceptible mechanical loads in conscious humans
Authors: Kobylarz E. J. , Daubenspeck J. A.
Published: December 2017

We used an esophageal electrode to measure the amplitude and neural inspiratory and expiratory (N TE) timing responses of crural diaphragmatic electrical activity in response to flow-resistive (R) and elastic (E) loads at or below the threshold for conscious detection, applied pseudorandomly to the oral airway of eight normal subjects. We observed a rapid first-breath neural reflex that modified respiratory timing such that N TE lengthened significantly in response to R loads in six of eight subjects and shortened in response to E loading in six of seven subjects. The prolongation of N TE with R loading resulted primarily from lengthening the portion of N TE during which phasic activity in the diaphragm is absent (TE NDIA), whereas E loading shortened N TE mainly by reducing TE NDIA. Most subjects responded to both types of loading by decreasing mean tonic diaphragmatic activity, the average level of muscle activity that exists when no phasic changes are occurring, as well as its variability. The observed timing responses are consistent in direction with optimally adaptive pattern regulation, whereas the modulation of tonic activity may be useful in neural regulation of end-expiratory lung volume.
Changes in respiratory muscle activity in conscious cats during experimental dives at 101 ATA
Authors: Burnet H. , Lenoir P. , Jammes Y.
Published: December 2017

The rationale for the present study was to test the hypothesis that increased work of breathing during experimental deep diving may lead to respiratory muscle fatigue. For this purpose, electromyograms (EMGs) of respiratory and skeletal muscles, plus electrocardiogram and electroencephalogram (EEG) derivatives, were continuously recorded in conscious cats. In each muscle group, the ratio of power in a high (H) to that in a low (L) band of EMG frequencies was computed. Direct diaphragmatic stimulation in selected animals produced a mass action potential to obtain the muscle fiber conduction velocity (MFCV). The maximal pressure was 101 ATA (1,000 msw) with a maximal duration of 72 h. Four cats breathed an He-O2 mixture and five others a ternary mixture (10% N2 in He-O2). Inspired O2 partial pressure was 350 Torr. With the He-O2 mixture, all the animals died within 2–54 h during the study at maximal depth. EEG signs of high-pressure nervous syndrome (HPNS) were present in all cats, and low-frequency (11–14 Hz) hyperbaric tremor discontinuously contaminated all EMG tracings. The H/L ratio computed from diaphragmatic and intercostal muscle EMGs increased after 12 h at 101 ATA. With the He-N2–O2 mixture, the cats survived until the end of the sojourn at 101 ATA, during which no hyperbaric tremor was detected from EMG tracings, and EEG signs of HPNS were weak or absent. From 31 ATA, the H/L ratio decreased significantly in respiratory but not in skeletal muscles; this was associated with decreased MFCV in the diaphragm after several hours at maximal depth.(ABSTRACT TRUNCATED AT 250 WORDS)
Pulmonary venous pressure increases during alveolar hypoxia in isolated lungs of newborn pigs
Authors: Fike C. D. , Kaplowitz M. R.
Published: December 2017

The purpose of this study was to determine whether pulmonary venous pressure increases during alveolar hypoxia in lungs of newborn pigs. We isolated and perfused with blood the lungs from seven newborn pigs, 6–7 days old. We maintained blood flow constant at 50 ml.min-1.kg-1 and continuously monitored pulmonary arterial and left atrial pressures. Using the micropuncture technique, we measured pressures in 10 to 60-microns-diam venules during inflation with normoxic (21% O2–69–74% N2–5–10% CO2) and hypoxic (90–95% N2–5–10% CO2) gas mixtures. PO2 was 142 +/- 21 Torr during normoxia and 20 +/- 4 Torr during hypoxia. During micropuncture we inflated the lungs to a constant airway pressure of 5 cmH2O and kept left atrial pressure greater than airway pressure (zone 3). During hypoxia, pulmonary arterial pressure increased by 69 +/- 24% and pressure in small venules increased by 40 +/- 23%. These results are similar to those obtained with newborn lambs and ferrets but differ from results with newborn rabbits. The site of hypoxic vasoconstriction in newborn lungs is species dependent.
Skeletal muscle atrophy in response to 14 days of weightlessness: vastus medialis
Authors: Musacchia X. J. , Steffen J. M. , Fell R. D. , Dombrowski M. J. , Oganov V. W. , Ilyina-Kakueva E. I.
Published: December 2017

The vastus medialis (VM) from rats after 14 days of microgravity on COSMOS 2044 (F) was compared with VM from tail-suspended hindlimb-unloaded rats (T) and ground controls, including vivarium (V), synchronous (S), and basal (B) animals. The VM is composed chiefly of fast-twitch fibers; however, it contains a deep portion closer to the bone with mixed slow- and fast-twitch fibers. In the mixed-fiber portion, type I and II fiber areas were significantly reduced in F animals. In the homogeneous portion with chiefly fast-twitch fibers, F rats also showed reductions in cross-sectional areas compared with T, V, and B but not S rats. Fiber densities (fibers/mm2) were greatest in VM from F rats. Capillary density changes paralleled fiber density changes. F animals have significantly greater density of capillaries in the mixed-fiber portion. Concentrations of protein, RNA, and DNA were highest in V controls, whereas F rats had the lowest level of total RNA. Lactate dehydrogenase activity, one measure of anaerobic capacity, was greater in F than in S rats. Citrate synthase activity, a measure of oxidative capacity, showed no significant differences between groups. Although triglyceride stores of VM were greater in F than in T rats, there were no significant differences from any of the control groups. It was concluded that VM wet weights may be a less sensitive measure of atrophy than the fiber area measurements. Fiber area decreases and fiber density increases in F animals were quantitatively comparable to those in soleus and extensor digitorum longus after 7 days of weightless flight in Spacelab 3. Our results suggest that VM shows measurable responses to weightlessness.
Cardiac morphology after conditions of microgravity during COSMOS 2044
Authors: Goldstein M. A. , Edwards R. J. , Schroeter J. P.
Published: December 2017

Light- and electron-microscopic studies were performed on cardiac muscle from rats flown on COS-MOS 2044 and from four control groups. Average cross-sectional area of myofibers was measured by video analysis of the light-microscopic images of papillary and ventricular muscle samples from all animals. This cross-sectional area was significantly decreased in flight rats (P = 0.03) compared with synchronous controls. Additional findings at the electron-microscopic level consistent with this atrophy were obtained by stereological analysis and optical diffraction analysis of papillary muscle samples. Slightly higher mitochondrial volume density values and mitochondria-to-myofibril ratios as well as normal A-band spacings (d1,0) and Z-band spacings of myofibrils were observed in the tail-suspension and flight groups. General morphological features similar to those in ventricular samples from the previous COSMOS 1887 flight were observed.
Coordination of wingbeat and respiration in the Canada goose. I. Passive wing flapping
Authors: Funk G. D. , Milsom W. K. , Steeves J. D.
Published: December 2017

The effects of passive wing flapping on respiratory pattern were examined in decerebrate Canada geese. The birds were suspended dorsally with two spine clamps while the extended wings were continuously moved up and down with a device designed to reproduce actual wing flapping. Passive wing motion entrained respiration over limited ranges by both increasing and decreasing the respiratory period relative to rest. All ratios of wingbeat frequency to respiratory frequency seen during free flight (Soc. Neurosci. Abstr. 15: 391, 1989) were produced during passive wing flapping. In addition, the phase relationship between wingbeat frequency and respiratory frequency, inspiration starting near the peak of wing upstroke, was similar to that seen during free flight and was unaffected by perturbations of the wing-flapping cycle. Removal of all afferent activity from the wings did not affect the ability of continuous passive wing movement to entrain respiration. However, feedback from the wings was required to produce rapid within-breath shifts in the respiratory period in response to single wing flaps. In conclusion, although feedback from the chest wall/lung may be more important in producing entrainment during the stable conditions of passive wing flapping, wing-related feedback may be critically involved in mediating the rapid adjustments in respiratory pattern required to maintain coordination between wing and respiratory movements during free flight.
Lung and chest wall impedances in the dog in normal range of breathing: effects of pulmonary edema
Authors: Barnas G. M. , Stamenovic D. , Lutchen K. R.
Published: December 2017

We evaluated the effect of pulmonary edema on the frequency (f) and tidal volume (VT) dependences of respiratory system mechanical properties in the normal ranges of breathing. We measured resistance and elastance of the lungs (RL and EL) and chest wall of four anesthetized-paralyzed dogs during sinusoidal volume oscillations at the trachea (50–300 ml, 0.2–2 Hz), delivered at a constant mean airway pressure. Measurements were made before and after severe pulmonary edema was produced by injection of 0.06 ml/kg oleic acid into the right atrium. Chest wall properties were not changed by the injection. Before oleic acid, EL increased slightly with increasing f in each dog but was independent of VT. RL decreased slightly and was independent of VT from 0.2 to 0.4 Hz, but above 0.4 Hz it tended to increase with increasing flow, presumably due to the airway contribution. After oleic acid injection, EL and RL increased greatly. Large negative dependences of EL on VT and of RL on f were also evident, so that EL and RL after oleic acid changed two- and fivefold, respectively, within the ranges of f and VT studied. We conclude that severe pulmonary edema changes lung properties so as to make behavior VT dependent (i.e., nonlinear) and very frequency dependent in the normal range of breathing.
Hyperoxic exposure enhances airway reactivity of newborn guinea pigs
Authors: Uyehara C. F. , Pichoff B. E. , Sim H. H. , Uemura H. S. , Nakamura K. T.
Published: December 2017

To determine whether altered airway smooth muscle contractility contributes to airway hyperreactivity resulting from hyperoxic exposure, in vitro contractile responses of airways to two physiological constrictors, acetylcholine (10(-9) to 10(-4) M) and histamine (10(-8) to 10(-4) M), were examined. Extrathoracic trachea, intrathoracic trachea, and bronchus from 1- to 2-day-old (newborn) guinea pigs exposed to 85% oxygen for 84 h were compared with tissues obtained from newborns reared in room air. Responses in the presence and absence of aspirin (ASA; 10(-3) M) were compared. Hyperoxic exposure did not affect the histology of the airway epithelia. Contractile responses to acetylcholine and histamine were similar. Without ASA, maximal tensions generated were higher in both extrathoracic and intrathoracic trachea obtained from hyperoxia-exposed neonates than in trachea from newborns reared in room air. ASA caused maximal tensions of trachea from newborns reared in room air to increase but did not affect the already increased contractility of trachea from hyperoxia-exposed animals; the tensions achieved in hyperoxic tissues with and without ASA were similar to the hyperactive responses induced by ASA in tissues from animals reared in room air. Bronchi showed responses similar to those seen in tracheal segments. Thus, despite no apparent histological effect on the airway epithelium, hyperoxic exposure seems to increase airway smooth muscle contractility, is nonspecific for different constricting agents, and shows no regional differences in airway reactivity.
Mechanics of the parasternal intercostals in prone dogs: statics and dynamics
Authors: De Troyer A. , Farkas G.
Published: December 2017

It is well established that the parasternal intercostal muscles in supine dogs play a major role in causing the inspiratory elevation of the ribs. This posture, however, is not physiological in the dog. In the present study, we measured the electromyographic (EMG) activity and the respiratory changes in length of these muscles in the prone (standing) and supine postures in seven anesthetized spontaneously breathing dogs. With a change from the supine to the prone posture, the parasternal intercostals showed a 3.2% reduction in their relaxation length (Lr), but their mechanical behavior was essentially unchanged. Thus, the muscles continued to shorten below Lr during inspiration and to lengthen beyond Lr during expiration. With the adoption of the prone posture, the amount of parasternal inspiratory EMG activity and the amount of inspiratory muscle shortening each increased by 30–35%. Furthermore, when the parasternal intercostal in a single interspace was selectively denervated, the shortening of the muscle during inspiration in both postures was virtually eliminated. These observations indicate that in the dog the parasternal intercostals still play a major role in causing the inspiratory elevation of the ribs in the prone posture. These observations also suggest that these muscles in prone animals continue to operate on the descending limb of their length-tension curve.
Effects of tube thoracostomy on pleural fluid characteristics in sheep
Authors: Carvalho P. , Kirk W. , Butler J. , Charan N. B.
Published: December 2017

We studied the pleural inflammatory response to tube thoracostomy by inserting an Argyle 32-Fr tube in the pleural space of 10 anesthetized sheep. An experimental pleural effusion was created by infusion of sterile normal saline (10 ml/kg) into the pleural space, and the animals were allowed to recover. Systemic blood and experimental pleural effusion (EPE) samples were obtained at time 0, 30 min, hourly for 6 h, and at 6-h intervals for a total of 48 h. EPE white cell count rose from 125 +/- 125 to 6,323 +/- 2,268/microliters (SE) at 6 h (P < 0.05) but showed marked variability at 42 and 48 h (P < 0.05), with values ranging from 8,000 to 22,000/microliters. The systemic white cell count rose from 5,195 +/- 914 to 9,640 +/- 1,110/microliters (P < 0.01) within the first 12 h and then remained stable. EPE protein increased from 0 +/- 0 to 3.73 +/- 0.2 g/dl at 48 h (P < 0.05). EPE lactate dehydrogenase rose from 44 +/- 12 IU/l to a peak of 638 +/- 55 IU/l at 24 h (P < 0.05). EPE glucose was significantly lower than serum glucose at 36, 42, and 48 h (P < 0.05). These data indicate that chest tube placement rapidly induces significant pleural inflammation and results in formation of a sterile exudate.
Arterial blood gas tensions during breath-hold diving in the Korean ama
Authors: Qvist J. , Hurford W. E. , Park Y. S. , Radermacher P. , Falke K. J. , Ahn D. W. , Guyton G. P. , Stanek K. S. , Hong S. K. , Weber R. E. , et al.
Published: December 2017

Korean female unassisted divers (cachido ama) breath-hold dive > 100 times to depths of 3–7 m during a work day. We sought to determine the extent of arterial hypoxemia during normal working dives and reasonable time limits for breath-hold diving by measuring radial artery blood gas tensions and pH in five cachido ama who dove to a fixed depth of 4–5 m and then continued to breath hold for various times after their return to the surface. Eighty-two blood samples were withdrawn from indwelling radial artery catheters during 37 ocean dives. We measured compression hyperoxia [arterial PO2 = 141 +/- 24 (SD) Torr] and hypercapnia (arterial PCO2 = 46.6 +/- 2.4 Torr) at depth. Mean arterial PO2 near the end of breath-hold dives lasting 32–95 s (62 +/- 14 s) was decreased (62.6 +/- 13.5 Torr). Mean arterial PCO2 reached 49.9 +/- 5.4 Torr. Complete return of these values to their baseline did not occur until 15–20 s after breathing was resumed. In dives of usual working duration (< 30 s), blood gas tensions remained within normal ranges. Detailed analysis of hemoglobin components and intrinsic oxygenation properties revealed no evidence for adaptive changes that could increase the tolerance of the ama to hypoxic or hypothermic conditions associated with repetitive diving.
Ventilatory pattern after hypoxic stimulation during wakefulness and NREM sleep
Authors: Gleeson K. , Sweer L. W.
Published: December 2017

The ventilatory after-discharge mechanism (VAD) may stabilize ventilation (VE) after hyperventilation but has not been studied in detail in humans. Several studies conducted during wakefulness suggest that VAD is present, although none has been conducted during sleep, when disordered ventilation is most common. We conducted two experiments during wakefulness and non-rapid-eye-movement (NREM) sleep in 14 healthy young men to characterize the ventilatory response after termination of a 45- to 60-s 10–12% O2 hypoxic stimulus. Eight subjects had triplicate hypoxic trials terminated by 100% O2 during wakefulness and NREM sleep. Hypoxia caused a drop in arterial O2 saturation to 78.5 +/- 0.5%, an increase in VE of 4.4 +/- 0.6 l/min, and a decrease in end-tidal PCO2 of 4.4 +/- 0.4 Torr during wakefulness, with no significant differences during sleep. When the hypoxia was terminated with 100% O2, VE was variable within and between subjects during wakefulness. During sleep, all subjects developed hypopnea (VE < 67% baseline) with a mean decrease of 65.5 +/- 7.8% at the onset of hyperoxia (P < 0.05 compared with baseline VE). We hypothesized that this uniform decrease in VE might be due to the nonphysiological hyperoxia employed. We therefore studied six additional subjects, all during NREM sleep, with identical hypoxic stimulation of breathing terminated by 100% O2 or room air. We again found that termination of hypoxia with 100% O2 produced uniform hypoventilation. However, when the identical stimulus was terminated with room air, no hypoventilation occurred.(ABSTRACT TRUNCATED AT 250 WORDS)
Laryngeal and pump muscle activities during CO2 breathing in neonates
Authors: Wozniak J. A. , Hutchison A. A. , Kosch P. C.
Published: December 2017

Term human newborns were challenged with a 2–3% CO2 gas mixture during quiet sleep. A common ventilatory response, consisting of increased tidal volume with no change in respiratory frequency or timing, was observed in all eight subjects. Minute ventilation and mean inspiratory and expiratory flow rates were elevated in all eight subjects [38 +/- 8 (SE), 38 +/- 22, and 39 +/- 9%, respectively]. Diaphragm, intercostal, and posterior cricoarytenoid (PCA) muscle activities during inspiration were increased in four of eight, six of eight, and seven of eight subjects, respectively Changes in intercostal and PCA muscle activities correlated with changes in inspiratory flow rates (r = 0.77 and 0.66, respectively). Diaphragmatic braking of expiratory airflow varied between subjects during room air breathing and did not change in six subjects with CO2 breathing. The remaining two subjects increased postinspiratory inspiratory diaphragmatic activity. Baseline expiratory PCA activity was augmented with CO2 breathing in six of eight subjects and correlated with increases in mean expiratory airflow (r = 0.76). The newborn infant is capable of using a variety of breathing strategies to augment tidal volume and minute ventilation, and control of the upper airway appears to be critical in modulating airflow during CO2 breathing.
Effects of high-frequency ventilation and PEEP on carotid baroreceptor reflexes
Authors: Sham J. S. , Mitzner W. , Fitzgerald R. S.
Published: December 2017

We tested the hypothesis that altering the pattern and/or magnitude of discharge of pulmonary stretch receptors (PSRs) would alter baroreceptor reflexes in anesthetized aortic-denervated cats. Carotid baroreceptor control of mean arterial pressure (MAP), heart rate (HR), and hindlimb perfusion pressure (PPhl) was examined by changing carotid sinus pressure (CSP) from 50 to 225 mmHg. The pattern of PSR discharge was changed by switching conventional mechanical ventilation (CMV) to high-frequency ventilation (HFV). Magnitude of PSR discharge was altered by changing positive end-expiratory pressure (PEEP). Altering the discharge pattern of PSR had no effect on CSP-MAP or CSP-PPhl relationships; small changes in HR were observed. Increasing PSR activity by increasing PEEP during CMV (from 3 to 9 cmH2O) depressed CSP-MAP relationship, set point, and threshold pressure. However, the depression in CSP-MAP relationship and set point during PEEP was unrelated to PSR activation, because these changes were not abolished after bilateral vagotomy. CSP-PPhl relationship was significantly elevated during PEEP before and after vagotomy, suggesting activation of a nonvagally mediated vasoconstrictory mechanism instead of PSR-mediated depressor reflex. CSP-HR relationship during PEEP showed a slight elevation, which was abolished after vagotomy. We conclude that despite minor increases in HR, altering the pattern of magnitude of PSR activity with HFV and PEEP has no significant effect on carotid baroreceptor regulation of systemic circulation. Hemodynamic changes observed during PEEP were likely due to its mechanical effect on cardiac output and activation of other cardiopulmonary receptors rather than to the increase in PSR activity.
On the preservation and regulation of vascular tone in arteriovenous anastomoses during anesthesia
Authors: Den Boer M. O. , Van Woerkens L. J. , Somers J. A. , Duncker D. J. , Lachmann B. , Saxena P. R. , Verdouw P. D.
Published: December 2017

In conscious pigs, arteriovenous anastomoses (AVAs) are in a constricted state so that < 5% of intra-atrially injected radioactive (15-microns-diam) microspheres are shunted to the lungs. Many of the anesthetic regimens frequently used in cardiovascular research dilate AVAs, thereby greatly increasing the percentage of microspheres reaching the lungs. This may seriously limit extrapolation of results obtained under anesthesia to the conscious state. We now describe that anesthesia with a combination of fentanyl and thiopental preserves the tone of AVAs, maintaining shunting under 4% of cardiac output. Furthermore, we studied in the carotid circulation of this model whether norepinephrine or 5-hydroxy-tryptamine (5-HT), both contained in perivascular nerves, is responsible for this tone. Consecutive antagonism of alpha 1-, alpha 2-, 5-HT1, and 5-HT2 receptors was obtained by sequential injection of prazosin, phentolamine, ketanserin, and methiothepin. Prazosin increased AVA blood flow, partly at the expense of extracerebral tissue blood flow, but preserved cerebral blood flow. None of the other antagonists had any additional significant effect. Therefore, in this model the tone in AVAs seems to be maintained by sympathetic norepinephrine-containing nerves via alpha 1-adrenoceptors.
Effect of ventilation inhomogeneity on "intrabreath" measurements of diffusing capacity in normal subjects
Authors: Cotton D. J. , Prabhu M. B. , Mink J. T. , Graham B. L.
Published: December 2017

In normal seated subjects we increased single-breath ventilation inhomogeneity by changing both the preinspiratory lung volume and breath-hold time and examined the ensuing effects on two different techniques of measuring the diffusing capacity of the lung for carbon monoxide (DLCO). We measured the mean single-breath DLCO using the three-equation method (DLCOSB-3EQ) and also measured DLCO over discrete intervals during exhalation by the "intrabreath" method (DLCOexhaled). We assessed the distribution of ventilation using the normalized phase III slope for helium (SN). DLCOSB-3EQ was unaffected by preinspiratory lung volume and breath-hold time. DLCOexhaled increased with increasing preinspiratory lung volume and decreased with increasing breath-hold time. These changes correlated with the simultaneously observed changes in ventilation inhomogeneity as measured by SN (P < 0.01). We conclude that measurements of DLCOexhaled do not accurately reflect the mean DLCO. Intrabreath methods of measuring DLCO are based on the slope of the exhaled CO concentration curve, which is affected by both ventilation and diffusion inhomogeneities. Although DLCOexhaled may theoretically provide information about the distribution of CO uptake, the concomitant effects of ventilation nonuniformity on DLCOexhaled may mimic or mask the effects of diffusion nonuniformity.
Washout of protein in dog lung lymph
Authors: Garewal D. , Gallagher H. , Drake R. E. , Gabel J. C.
Published: December 2017

After an increase in microvascular filtration rate, lung lymph may contain protein washed from the tissue spaces plus protein from the filtrate. If so, then the lymphatic protein concentration may be significantly higher than the filtrate protein concentration (Cf). To test this hypothesis, we decreased the plasma protein concentration from 5.1 +/- 0.6 to 0.54 +/- 0.15 g/dl and increased the pulmonary microvascular filtration rate in four dogs. We estimated Cf to be 0.16 +/- 0.05 g/dl after we reduced the plasma protein concentration, and the lymphatic protein concentration (0.43 +/- 0.04 g/dl) was significantly greater than Cf. Our results indicate that lung microvascular membrane reflection coefficients estimated from lung lymph data may be too low. However, the amount of error caused by tissue protein washout is probably small. To account for the protein washout error, we estimated the lung microvascular membrane reflection coefficient to be approximately 0.74–0.76 instead of the approximately 0.70 previously reported for dogs (J. C. Gabel et al. J. Appl. Physiol. 55: 866–869, 1983).
Effects of oxygen tension and glucose concentration on ischemic injury in ventilated ferret lungs
Authors: Becker P. M. , Pearse D. B. , Sylvester J. T.
Published: December 2017

In the ventilated ischemic lung, oxygen tension will increase at a time when glucose depletion may impair antioxidant defenses, thereby predisposing the lung to injury mediated by oxygen radicals. In the unventilated ischemic lung, however, glucose depletion in the setting of low oxygen tension may decrease production of ATP, leading to injury by a different mechanism. In this study, we evaluated the role of both oxygen tension and glucose concentration on ischemic injury in isolated ferret lungs. Injury, defined as an increase in vascular permeability, was assessed by measurement of filtration coefficient (Kf) and osmotic reflection coefficient for albumin (sigma alb) after 3 h of normothermic (37 degrees C) ischemia without reperfusion. Lungs were ventilated with either 95% O2–5% CO2 or 0% O2–5% CO2. The vasculature was flushed with physiological salt solution containing either 15 mM glucose (hyperoxia-glucose, anoxia-glucose), 15 mM sucrose (hyperoxia-sucrose, anoxia-sucrose), or no substrate (hyperoxia-no substrate, anoxia-no substrate) (n = 6 for each condition). Kf and sigma alb in hyperoxia-no substrate group did not differ from values in minimally ischemic normoxic normoglycemic ferret lungs. Without glucose, ischemic injury was worse in anoxic than in hyperoxic lungs. With glucose, ischemic injury was worse in hyperoxic than in anoxic lungs. Glucose exacerbated injury in hyperoxic, but not anoxic, lungs. These results indicate that ischemic injury in these lungs depended on both oxygen tension and glucose concentration and suggest that both oxygen radical generation and ATP depletion during ischemia may contribute to the development of this injury.
Capillary oxygen transport during severe hypoxia: role of hemoglobin oxygen affinity
Authors: Stein J. C. , Ellsworth M. L.
Published: December 2017

The efficacy of an increased hemoglobin oxygen affinity [decreased oxygen half-saturation pressure of hemoglobin (P50)] on capillary oxygen transport was evaluated in the hamster retractor muscle under conditions of a severely limited oxygen supply resulting from the combined effects of a 40% reduction in systemic hematocrit and hypoxic ventilation (inspired oxygen fraction 0.1). Two groups of hamsters were utilized: one with a normal oxygen affinity (untreated; P50 = 26.1 +/- 2.4 Torr) and one with an increased oxygen affinity (treated; P50 = 15.7 +/- 1.4 Torr) induced by the chronic short-term administration of sodium cyanate. Using in vivo video microscopy and image analysis techniques, we determined oxygen saturation and associated hemodynamics at both ends of the capillary network. During hypoxic ventilation, the decrease in oxygen saturation across the network was 3.6% for untreated animals compared with 9.9% for treated animals. During hypoxia, estimated end-capillary PO2 was significantly higher in the untreated animals. These data indicate that, at the capillary level, a decreased P50 is advantageous for tissue oxygenation when oxygen supply is severely compromised, because normal oxygen losses in capillaries are maintained in treated but not in untreated animals. The data are consistent with the presence of a diffusion limitation for oxygen during severe hypoxia in animals with a normal hemoglobin oxygen affinity.
Age and training alter collagen characteristics in fast- and slow-twitch rat limb muscle
Authors: Zimmerman S. D. , McCormick R. J. , Vadlamudi R. K. , Thomas D. P.
Published: December 2017

This study evaluated the single and interactive effects of age and training status on selected collagen parameters in two rodent locomotor skeletal muscles contrasting in fiber type composition. Gastrocnemius (GAST) and soleus (SOL) muscles from both trained (10 wk of daily treadmill running) and sedentary young adult (5-mo-old), middle-aged (15-mo-old), and old (23-mo-old) female Fischer 344 rats were evaluated for concentrations of collagen (measured by hydroxyproline concentration ([OH-Pro])) and of the predominant nonreducible lysine aldehyde-derived collagen cross-link hydroxylysylpyridinoline ([HP]). Maximal aerobic capacity was significantly elevated in all three trained groups compared with sedentary age-matched control groups. Slow-twitch SOL had a significantly higher [OH-Pro] than fast-twitch GAST (P < 0.05). Although aging had no effect on [OH-Pro] in GAST, in SOL a significant increase with age was seen (P < 0.02). In sedentary rats both GAST and SOL [HP] increased with age, with this increase being more pronounced for SOL. Additionally, although training had no effect on the aging-associated increase in GAST [HP], it prevented the rise seen in SOL. The observed training-induced reduction in SOL [HP] presumably reflects exercise recruitment and subsequent stimulation of collagen synthesis and degradation rates in this muscle. We conclude that both aging and training affect the extracellular matrix in rodent limb skeletal muscle.