bluuebunny/crossref_metadata_2025 huggingface dataset:
Ventral medullary pH and ventilatory responses to hyperperfusion and hypoxia
Authors: Neubauer J. A. , Santiago T. V. , Posner M. A. , Edelman N. H.
Published: December 2017

The role of a sudden increase in brain perfusion on ventral medullary surface pH (Vm pH) and minute ventilation (VI) was assessed in anesthetized peripherally chemo denervated cats. Acute hypertension (AH), produced by rapid inflation of an aortic balloon, and hypoxemia, produced with either inhalation of 1% CO (COHx) or inhalation of a hypoxic gas (HHx), were used to increase brain blood flow. In the AH group, increasing arterial blood pressure (from 122 +/- 3 to 180 +/- 5 mmHg) caused a rapid (less than 5 s) increase in Vm pH in every trial (n = 18). Associated with the mean peak increases in Vm pH (0.003 +/- 0.0004 pH units) were significant decrease in tidal volume (7–9%). In the COHx group, 17% HbCO caused a significant increase in Vm pH (0.003 +/- 0.0005 pH unit) and diminution of VI (9%). Further increases in HbCO caused a progressive ventral medullary acidosis and greater reductions in VI. The results from the HHX group were qualitatively similar to the COHx group; there was a biphasic response of Vm pH, i.e., an initial increase in Vm pH (0.008 +/- 0.001) followed by a steady decrease in Vm pH, with reductions in VI associated with both phases. We conclude that hyperperfusion, per se, produces an increase in Vm pH and a reduction in VI equivalent in magnitude to that predicted from the CO2 stimulus-response curve; the alkalotic shift in Vm pH and concomitant diminution in VI associated with mild hypoxia is probably related to an increase in ventral medullary perfusion; and the ventilatory depression associated with the medullary acidosis of moderate brain hypoxia must be attributed to another mechanism.
An electromyographic study of elbow motion during postexercise muscle soreness
Authors: Howell J. N. , Chila A. G. , Ford G. , David D. , Gates T.
Published: December 2017

Postexercise muscle soreness was induced in the elbow flexors of human volunteer subjects through the use of a regimen of eccentric contractions. Physical examination before and 48 h after the exercise included measurements of range of elbow motion at the elbow and of arm diameter. Electromyographic (EMG) observations, utilizing fine wire electrodes introduced into each of the elbow flexors, were carried out before and 48 h after the exercise. These observations included resting EMG levels, EMG activity under various isometric loads, and activity during active and passive extensions. The soreness induced was accompanied by a reduction in resting elbow angle while the subjects stood with arms relaxed at their sides, decreased range of both flexion and extension of the elbow, and swelling of the arm. EMG measurements showed no increase in EMG activity as the sore arms were extended passively at the elbow, indicating that the extra resistance to extension associated with the soreness was not a result of stretch receptor-induced activity in the flexors. The results rule out the possibility that neuromuscular activity is responsible for the restriction of motion and are consistent with the idea that edematous changes within the perimuscular connective tissue alter the elastic behavior of the muscles and cause restriction of motion.
Altered breathing pattern elicited by stimulation of abdominal visceral afferents
Authors: Prabhakar N. R. , Marek W. , Loeschcke H. H.
Published: December 2017

The effect of stimulation of afferent mesenteric nerves on tidal volume (VT), phrenic nerve, and external intercostal muscle activities was studied in anesthetized spontaneously breathing cats. Both mechanical distension of the small intestine and electrical stimulation of the mesenteric nerves resulted in an initial inspiratory inhibition of VT followed by a gradual recovery above the prestimulus controls. Changes in VT were accompanied by a depression of phrenic nerve activity and an excitation of external intercostal muscle activity. During the recovery phase of VT, the amplitude of phrenic nerve activity returned only partially, whereas the activity of the external intercostal muscle was greater than the prestimulus controls. In a second group of experiments, brief tetanic stimulation at the beginning of inspiration led to a complete and maintained inhibition of phrenic nerve activity but with a simultaneous excitation of external intercostal muscle activity and without any change in VT; whereas expiratory stimulation caused a decrease in expiratory abdominal muscle activity, without changing the peak amplitude of phrenic nerve activity. The respiratory changes observed with distension of the small intestine were abolished after denervation of the mesenteric plexus. It is concluded that activation of the visceral afferents of the mesenteric region reflexly changes diaphragmatic breathing to intercostal breathing. It is assumed that such a type of breathing pattern may occur in pregnancy and in pathophysiological situations involving splanchnic viscera.
Lung damage and pulmonary uptake of serotonin in intact dogs
Authors: Dawson C. A. , Christensen C. W. , Rickaby D. A. , Linehan J. H. , Johnston M. R.
Published: December 2017

We examined the influence of glass bead embolization and oleic acid, dextran, and imipramine infusion on the pulmonary uptake of trace doses of [3H]serotonin and the extravascular volume accessible to [14C]antipyrine in anesthetized dogs. Embolization and imipramine decreased serotonin uptake by 53 and 61%, respectively, but no change was observed with oleic acid or dextran infusion. The extravascular volume accessible to the antipyrine was reduced by 77% after embolization and increased by 177 and approximately 44% after oleic acid and dextran infusion, respectively. The results suggest that when the perfused endothelial surface is sufficiently reduced, as with embolization, the uptake of trace doses of serotonin will be depressed. In addition, decreases in serotonin uptake in response to imipramine in this study and in response to certain endothelial toxins in other studies suggest that serotonin uptake can reveal certain kinds of changes in endothelial function. However, the lack of a response to oleic acid-induced damage in the present study suggests that serotonin uptake is not sensitive to all forms of endothelial damage.
Effects of chronic right-to-left cardiac shunt on hypoxic sensitivity of mongrel dogs
Authors: Von Colditz J. H. , Coon R. L. , Clifford P. S. , Igler F. O. , Litwin S. B. , Kampine J. P.
Published: December 2017

Resting ventilation (VI), blood gases, hypoxic sensitivity, and the ventilatory responses to intravenous sodium cyanide (NaCN, 100 micrograms/kg), doxapram (DOX, 500 micrograms/kg), and dopamine (DOPA, 20 micrograms/kg) were analyzed in four normal mongrel dogs (group I-N) and seven mongrel dogs with chronic (5–11 yr) right-to-left cardiac shunt (group II). The group I-N animals were also studied during steady-state isocapnic hypoxia (group I-H). The shunt procedure used for these studies produced a model for ventilatory studies during chronic shunt hypoxemia. The increases in VI per percent decrease in O2 saturation, which occurred during a four-breath N2 test, were 30, 43, and 13 ml X kg-1 X min-1 in groups I-N, I-H, and II, respectively. The decrease in hypoxic sensitivity of the group II animals, compared with groups I-N and I-H, occurred in the presence of an increase in PaCO2 from 21.9 to 26.0 Torr during the four-breath N2 test. A decrease in PaCO2 from 34.7 to 30.0 and from 33.6 to 30.4 Torr was observed in groups I-N and I-H. The response to DOX, a general analeptic agent, was greatest in group II and least in group I-N. However, the ventilatory responses to NaCN and DOPA were not sufficiently different among the three groups to suggest a difference in carotid body function as assessed by these drugs.
Clearance of mucus by simulated cough
Authors: King M. , Brock G. , Lundell C.
Published: December 2017

We examined the relationship between mucus rheology, depth of mucus layer, and clearance by simulated cough. A model trachea was constructed of rigid Plexiglas of rectangular cross section (1 X 2 X 35 cm). The bottom of the trachea was lined with mucus simulants, gels prepared from locust bean gum cross-linked with sodium borate. Cough was simulated by opening a solenoid valve connecting the model trachea to a pressurized tank. An upstream flow-constrictive element was used to shape the flow profile of the simulated cough to approximate the pattern seen in a normal adult. Clearance of mucus was quantitated by observing the movement of contrasting marker particles floating in the mucus layer. The median particle displacement per cough maneuver was defined as the clearance index (CI). We found that CI for any initial depth of mucus increased with the driving pressure in the tank. For a given driving pressure, CI increased linearly with increasing mucus depth. For a given driving pressure and depth, CI decreased with increasing mucus cross-link density. For mucus samples with comparable levels of dynamic viscosity, samples with higher elasticity cleared less well. Mucus clearance was associated with transient wave formation in the lining layer.
Modification of pulmonary oxygen toxicity by bleomycin treatment
Authors: Matalon S. , Harper W. V. , Goldinger J. M. , Nickerson P. A. , Olszowka J.
Published: December 2017

The purpose of this study was to determine whether pretreatment of rabbits with bleomycin would modify their response to 100% O2 and, if so, to identify the mechanism of this action. A single intratracheal injection of bleomycin (5 U/kg) resulted in a transient decrease of the arterial Po2, its mean value (+/- SE) 7 days postinjection being 59 +/- 3 Torr. All animals were either killed or exposed to 100% O2 35 days postinjection. At this time, arterial Po2 had returned to its control level. On the other hand, lung hydroxyproline content had doubled and static compliance and the total lung capacity had decreased by 22 and 31%, respectively, indicating the existence of significant lung fibrosis. Furthermore, activities of catalase and superoxide dismutase in lung homogenates were higher than control and were further augmented by exposure to 100% O2 for 64 h. These biochemical changes may account, at least in part, for the mitigation of the toxic effects of hyperoxia, as shown by the delayed appearance of arterial hypoxemia, and the 50% increase in survival time when bleomycin injected rabbits were exposed to 100% O2 35 days postinjection.
Respiratory mechanics in mechanically ventilated patients with respiratory failure
Authors: Rossi A. , Gottfried S. B. , Higgs B. D. , Zocchi L. , Grassino A. , Milic-Emili J.
Published: December 2017

In 11 mechanically ventilated patients, respiratory mechanics were measured 1) during constant flow inflation and 2) following end-inflation airway occlusion, as proposed in model analysis (J. Appl. Physiol. 58: 1840–1848, 1985. During the latter part of inflation, the relationship between driving pressure and lung volume change was linear, allowing determination of static respiratory elastance (Ers) and resistance (RT). The latter represents in each patient the maximum resistance value that can obtain with the prevailing time constant inhomogeneity. Following occlusion, Ers and RT were also obtained along with RT (min) which represents a minimum, i.e., resistance value that would obtain in the absence of time constant inhomogeneity. A discrepancy between inflation and occlusion Ers and RT was found only in the three patients without positive end-expiratory pressure, and could be attributed to recruitment of lung units during inflation. In all instances Ers and RT were higher than normal. RT(min) was lower in all patients than the corresponding values of RT, indicating that resistance was frequency dependent due to time constant inequalities. Changes in inflation rate did not affect Ers, while RT increased with increasing flow.
Role of microtubules in surfactant secretion
Authors: Brown L. A. , Pasquale S. M. , Longmore W. J.
Published: December 2017

In the isolated perfused rat lung and cultured type II cells, surfactant secretion and cellular adenosine 3′,5′-cyclic monophosphate (cAMP) content was stimulated by beta-adrenergic agonists. Isoproterenol-induced surfactant secretion was inhibited by the antimicrotubule agents colchicine and vinblastine. Incorporation of [3H]glycerol into disaturated phosphatidylcholine was augmented by beta-adrenergic agents but was not significantly different from the enhanced incorporation rate when colchicine was present. This suggests that the augmented incorporation of [3H]glycerol into disaturated phosphatidylcholine was a secondary response to storage depletion rather than direct cAMP stimulation. beta-Adrenergic agents shifted the equilibrium in the isolated perfused rat lung and cultured type II cells to favor microtubules. The stimulatory effect of 1.0 microM isoproterenol on tubulin polymerization was observed as early as 1 min and was augmented 2.8-fold at a half-maximal stimulation of 4 nM in cultured type II cells. Cytochalasin B, an antimicrofilament agent, potentiated the isoproterenol-induced secretion. These results suggest that an intact microtubule-microfilament system may be obligatory for enhanced surfactant secretion and that beta-adrenergic agents not only induce surfactant release but also tubulin polymerization.
Heat acclimation: role of norepinephrine in the anterior hypothalamus
Authors: Christman J. V. , Gisolfi C. V.
Published: December 2017

The hypothesis that anterior hypothalamic (AH) sensitivity to norepinephrine (NE) is altered by chronic exercise in the heat was tested in male Sprague-Dawley rats. Treadmill exercise 6 days/wk for 3 wk at 21 m/min was performed at 23 degrees C (control; C) or at 35 degrees C (heat acclimated; HA), progressing from 20 to 50 min/day in 2 wk. Time for core temperature (Tco) to rise from 39.5 to 40.5 degrees C during a heat-tolerance test after conditioning increased (P less than 0.05) in the HA group. To test for a change in AH sensitivity, the change in Tco to 2-, 5-, 10-, 20-, and 40-micrograms doses of NE injected bilaterally into the AH was determined after conditioning. Dose-response regression lines showed that exercise in the heat increased the slope and shifted the Tco-NE dose relation to the left. In a separate series of experiments on 6 sedentary(s), 10 C, and 10 HA animals, the amounts of NE, dopamine, and 3,4-dihydroxyphenylglycol (DOPEG) were determined by high-pressure liquid chromatography in the AH, median preoptic area (PO), cortex, and cerebellum after 9 wk of conditioning. Results showed that in the PO there was a significant increase in NE and DOPEG in the HA vs. C group and a trend of increasing NE from the S to C to HA groups. The data indicate that exercise in the heat increases NE-induced peripheral heat-dissipating capacity and increases catecholamine storage in the PO.
Pulmonary blood flow vs. gas volume at various perfusion pressures in rabbit lung
Authors: Beck K. C. , Lai-Fook S. J.
Published: December 2017

To obtain a detailed description of the dependence of pulmonary blood flow on changes in lung volume, we perfused isolated rabbit lungs with homologous blood at 37 degrees C while controlling vascular pressures during lung deflation. We set pulmonary arterial pressure (Ppa) and pulmonary venous pressure (Ppv) to constant values relative to alveolar pressure (Palv) to keep the effective driving pressure for flow constant during lung deflation from total lung capacity (TLC) to 25% TLC. The shapes of the flow vs. lung volume curves were dependent on the levels of Ppa-Palv and Ppv-Palv at which they were obtained. When Ppv greater than Palv throughout the lung (zone 3 conditions), flow increased as the lungs were deflated from TLC, independent of the level of Ppa-Palv. When Ppv less than Palv (zone 2 conditions) and Ppa-Palv was moderately high, flow increased as the lungs were deflated from 100 to approximately 50% TLC, then decreased at lower lung volumes. When Ppa - Palv was less than 10 cmH2O in zone 2 conditions, flow decreased monotonically during deflation from TLC. We concluded that the dependence of blood flow on lung volume is complex, which may be a reflection of the nonlinear pressure-diameter properties of pulmonary vessels.
Expiratory effects of vagal stimulation in newborn kittens
Authors: Trippenbach T. , Kelly G.
Published: December 2017

Expiratory effects of electrical stimulation of vagal afferents were studied in 12 kittens during the first week of life. Animals anesthetized with ketamine (30 mg/kg, im) and acepromazine (1.1 mg/kg, im), tracheostomized, and paralyzed were artificially ventilated after bilateral vagotomy. Rectified and “integrated” activity of the C5 root of phrenic nerve, systemic blood pressure, and the stimulus train were recorded. The optimal stimulus parameters for expiratory prolongation were chosen. The results varied between animals. We found three types of response: A, expiratory prolongation when stimulus was applied within the initial 80% of control expiratory time (TEc); beyond this delay, a decreased response or no effect was observed in four kittens; B, graded expiratory prolongation was recorded to the end of this phase in three kittens; and C, expiratory prolongation when stimulus delay was less than 40% of TEc and expiratory shortening when the stimulus given with greater delays was observed in one kitten. Nonsignificant effects were observed in the remaining four animals. Types A and B of response suggest activation of the slowly adapting pulmonary stretch receptors. However, amplitude of stimulus and frequency of pulses were higher than those used in adult animals. Type C response indicates that fibers from both rapidly and slowly adapting stretch receptors could be activated. Our results imply that if the expiratory insensitive phase is present in kittens, it can be affected by experimental conditions. This is in contradiction to characteristics of expiratory response to vagal stretch receptor input in adult cats.
Effects of histamine on bronchial artery blood flow and bronchomotor tone
Authors: Long W. M. , Sprung C. L. , el Fawal H. , Yerger L. D. , Eyre P. , Abraham W. M. , Wanner A.
Published: December 2017

The effects of aerosolized 5% histamine (10 breaths) on bronchial artery blood flow (Qbr), airflow resistance (RL), and pulmonary and systemic hemodynamics were studied in mechanically ventilated sheep anesthetized with pentobarbital sodium. Histamine increased mean Qbr and RL to 252 +/- 45 and 337 +/- 53% of base line, respectively. This effect was significantly different from base line for 30 min after challenge. The histamine-induced increase in RL was blocked by pretreatment with the histamine H1 receptor antagonist, chlorpheniramine, whereas the histamine-induced elevation in Qbr was prevented by the H2 antagonist, metiamide. Both responses were blocked only when both antagonists were present. Changes in Qbr were not directly associated with alterations in systemic and pulmonary hemodynamics or arterial blood gas composition. In vitro histamine caused a dose-dependent contraction of ovine bronchial artery strips that was prevented by H1 antagonist. The H2 agonist, impromidine, caused relaxation of precontracted arterial strips and was more potent and efficacious than histamine, whereas H1 agonists failed to elicit a relaxant response. Thus these findings indicate that histamine aerosol induces a vasodilation in the bronchial vascular bed; histamine has a direct effect on Qbr that is independent of alterations in RL, systemic and pulmonary hemodynamics, or arterial blood gas composition; and, histamine-induced bronchoconstriction is mediated predominantly by H1-receptors, whereas increased Qbr is controlled predominantly by H2-receptors, probably located in resistance vessels. This local effect of histamine on Qbr may have important implications in the pathophysiology of bronchial asthma and pulmonary edema.
Erythrocyte adenosine triphosphate depletion during voluntary hyperventilation
Authors: Stäubli M. , Ott P. , Waber U. , Stäuble U. P. , Jeanneret C. , Peheim E. , Straub P. W.
Published: December 2017

Page 1196: M. Sttäubli, P. Ott, U. Waber, U. P. Stäuble, C. Jeanneret, E. Peheim, and P. W. Straub. “Erythrocyte adenosine triphosphate depletion during voluntary hyperventilation.” Page 1198: the final entry in the left-hand column of Table 1 should read: Osmotic fragility, 50% hemolysis, %NaCl.
Differences in endogenous pyrogen fevers induced by iv and icv routes in rabbits
Authors: Stitt J. T. , Bernheim H. A.
Published: December 2017

We have compared the characteristics of fevers produced by endogenous pyrogen administered by the intravenous (iv) and by the intracerebroventricular (icv) routes in conscious rabbits. Fevers induced by the intracerebroventricular route have a longer latency to onset, a less steep rise in body temperature, and a longer time to peak elevation in body temperature than do fevers induced by the intravenous route. Furthermore, a dose of indomethacin (2 mg/kg) administered intravenously, which is effective in markedly attenuating fevers produced by the intravenous route, was completely without effect on fevers induced by the intracerebroventricular route. On the other hand, when indomethacin (500 micrograms) was infused intracerebroventricularly, it markedly reduced fevers induced by the subsequent injection of endogenous pyrogen into the contralateral cerebral ventricle, but such pretreatment had little effect on fevers elicited by intravenous injections of endogenous pyrogen. It is concluded that the sites of action of endogenous pyrogen in response to intravenous injections of pyrogen are different from those responding to intracerebroventricular injections of pyrogen and that this is manifest in several distinct differences in the characteristics of the two fevers. These results indicate that the intracerebroventricular model of fever production is not appropriate for the study of the normal pathogenesis of fever.
Effect of thermal history on the rat's response to varying environmental temperature
Authors: Gwosdow A. R. , Besch E. L.
Published: December 2017

After acclimating individually housed male rats to temperatures of either 24.5 +/- 0.1 or 29.2 +/- 0.1 degrees C for 14 days, randomly paired animals from each group were acutely exposed (3 h) in series to experimental temperatures between 18.0 and 34.5 degrees C in a controlled environment room. Relative humidity of 50 +/- 0.3% and a 12-h light-dark photoperiod (light from 0900 to 2100 h) were maintained. Metabolic rate (MR) and evaporative water loss (EWL) were-measured using an open-flow system; thermistors were used to measure the rectal (Tre) and tail skin (Tts) temperatures. MR was relatively constant over a temperature range of 22.2 to 27.0 degrees C for rats acclimated to 24.5 degrees C and 20.0 to 29.2 degrees C for rats acclimated to 29.2 degrees C. Above and below these ranges, MR for both groups was significantly (P less than 0.05) elevated. At their respective acclimation temperatures, the absolute Tre and Tts of 29.2 degrees C rats were maintained at an elevated level compared with 24.5 degrees C rats. Although EWL for both groups was relatively constant between 18.0 and 27.0 degrees C, 24.5 degrees C rats displayed higher EWL changes at most environmental temperatures above 27.0 degrees C. At 34.5 degrees C, 29.2 degrees C rats dissipated 26% more metabolic heat by evaporation compared with 24.5 degrees C rats. These data suggest that acclimation temperatures of rats affected the thermoneutral zone and alter the set-point temperature around which thermal responses are regulated.
Substrate usage during prolonged exercise following a preexercise meal
Authors: Coyle E. F. , Coggan A. R. , Hemmert M. K. , Lowe R. C. , Walters T. J.
Published: December 2017

The effect of a high-carbohydrate meal 4 h before 105 min of exercise at 70% of maximal O2 uptake was determined in seven endurance-trained cyclists and compared with exercise following a 16-h fast. The preexercise meal produced a transient elevation of plasma insulin and blood glucose, which returned to fasting basal levels prior to the initiation of exercise. The meal also resulted in a 42% elevation (P less than 0.05) of glycogen within the vastus lateralis at the beginning of exercise. The 1st h of exercise when subjects were fed was characterized by a 13–25% decline (P less than 0.05) in blood glucose concentration, a suppression of the normal increase in plasma free fatty acids and blood glycerol, and a 45% (P less than 0.05) greater rate of carbohydrate oxidation compared with exercise when subjects were fasted. After 105 min of exercise, there were no significant differences when subjects were fed or fasted regarding blood glucose levels, rate of carbohydrate oxidation, or muscle glycogen concentration. The greater muscle glycogen utilization (97 +/- 18 vs. 64 +/- 8 mmol glucosyl units X kg-1; P less than 0.05) and carbohydrate oxidation when subjects were fed appeared to be derived from the glycogen synthesized following the meal. These results indicate that preexercise feedings alter substrate availability despite a return of plasma insulin to fasting levels prior to exercise and that these effects persist until the 2nd h of exercise.
Effect of body orientation on regional lung expansion: a computed tomographic approach
Authors: Hoffman E. A.
Published: December 2017

The Dynamic Spatial Reconstructor (DSR) was used to study in vivo lung geometry and function. By replacing the lungs of three dogs with potato flakes and ping-pong balls of known air content and scanning these realistic phantoms in the DSR we have estimated accuracy of lung density to be within 7% and have demonstrated a high (+/- 3%) internal consistency (relative density within dogs). Change in total lung air content (y) as calculated from DSR volume imaging of anesthetized dogs matched the known inflation steps (x) to within 7% [range was 1–7% with a mean of 3 +/- 0.5% (SE)]. A gradient of decreasing percent lung air content was measured in the ventral-dorsal direction at functional residual capacity (FRC) in the supine body posture (y = 3.29% air content/cm lung height + 46.48% air content; r = 0.90). Regional lung air content change with lung inflation was greatest in the dependent lung regions. In contrast, regional lung air content at FRC was approximately uniform along the ventral-dorsal direction with the dog in the prone posture and was 66 +/- 0.6% (SE). Ventral-dorsal gradients in lung air content measured within an isogravimetric plane of the dogs in the left or right lateral body posture suggest that regional differences in lung air content cannot be explained solely on the basis of a direct gravitational effect on the lung. Evidence is presented to suggest a possible major role of the intrathoracic position of the mediastinal contents in determining these lung air content distributions.
Effect of body orientation on regional lung expansion in dog and sloth
Authors: Hoffman E. A. , Ritman E. L.
Published: December 2017

Recent studies (E.A. Hoffman, J. Appl. Physiol. 59: 468–480, 1985) using fast multisliced X-ray computed tomography have demonstrated a ventral-dorsal gradient of fractional lung air content (3.29% air/cm lung height) in supine dogs and an essentially uniform ventral-dorsal air content distribution in the prone dogs [mean = 66 +/- 0.6% (SE) air content]. Since the prone orientation is the dog's normal body posture, we sought to study an animal whose normal body posture was “opposite” to that of the dog. Four two-toed sloths were scanned in the Dynamic Spatial Reconstructor in the prone and supine postures. A supine fractional air content gradient was demonstrated with a regression equation of y = 2.09x + 74.3 (r = 0.92), where y is percent air content and x is vertical height in the lung, and ventral-dorsal air content distribution in the prone posture was uniform with a mean of 85 +/- 0.4% (SE) air content. The low functional residual capacity lung density in the sloth was attributable to unusually large alveoli. The mean heart volume-to-body weight ratio in the dogs was 16.4 +/- 0.6 (SE) ml/kg and that in the sloth was 7.3 +/- 0.4 (SE) ml/kg. Mean lung volume-to-body weight ratios for dogs and sloths were 57 +/- 7 (SE) and 89 +/- 6 ml/kg, respectively. Of particular interest was the fact that large changes in prone vs. supine rib cage and diaphragm geometry previously found in dogs did not occur in sloths, though significant alterations of ventral and dorsal lung geometry prone vs. supine were demonstrated, and lung shape changes in both dog and sloth are attributable to shifts in the intrathoracic position of mediastinal structures.
Specificity and sensitivity of noninvasive measurement of pulmonary vascular protein leak
Authors: Dauber I. M. , Pluss W. T. , VanGrondelle A. , Trow R. S. , Weil J. V.
Published: December 2017

Noninvasive techniques employing external counting of radiolabeled protein have the potential for measuring pulmonary vascular protein permeability, but their specificity and sensitivity remain unclear. We tested the specificity and sensitivity of a double-radioisotope method by injecting radiolabeled albumin (131I) and erythrocytes (99mTc) into anesthetized dogs and measuring the counts of each isotope for 150 min after injection with an external gamma probe fixed over the lung. We calculated the rate of increase of albumin counts measured by the probe (which reflects the rate at which protein leaks into the extravascular space). To assess permeability we normalized the rate of increase in albumin counts for changes in labeled erythrocyte signal to minimize influence of changes in vascular surface area and thus derived an albumin leak index. We measured the albumin leak index and gravimetric lung water during hydrostatic edema (acutely elevating left atrial pressure by left atrial balloon inflation: mean pulmonary arterial wedge pressure = 22.6 Torr) and in lung injury edema induced by high- (1.0 g/kg) and low-dose (0.25 g/kg) intravenous thiourea. To test specificity we compared hydrostatic and high-dose thiourea edema. The albumin leak index increased nearly fourfold from control after thiourea injury (27.2 +/- 2.3 X 10–4 vs. 7.6 +/- 0.9 X 10–4 min-1) but did not change from control levels after elevating left atrial pressure (8.9 +/- 1.2 X 10–4 min-1) despite comparable increases in gravimetric lung water. To test sensitivity we compared low-dose thiourea with controls. Following low-dose thiourea, the albumin leak index nearly doubled despite the absence of a measurable increase in lung water. We conclude that a noninvasive double radioisotope measurement of pulmonary vascular protein leak, employing external counting techniques and a simplified method of calculation, is specific for lung injury and is also sensitive enough to detect lung injury insufficient to produce detectable pulmonary edema.
Differential response of lung and liver of juvenile rats to choline deficiency
Authors: Yost R. W. , Chander A. , Fisher A. B.
Published: December 2017

The effect of choline deficiency on the lung lipids of actively growing male Sprague-Dawley rats was investigated using a washed soy protein diet deficient in choline and methionine (lipotrophic). The livers from deficient animals had a significantly increased total lipid content and decreased phosphatidylcholine (PC) content and PC-to-phosphatidylethanolamine ratio (P less than 0.01). Although lung free choline levels were decreased 40% compared with controls (P less than 0.05), the PC content of the whole lung homogenate was unchanged. However, disaturated phosphatidylcholine from animals receiving the lipotrophic diet was significantly increased in the lavage and proportionally decreased in the lavaged lung tissue compared with controls (P less than 0.01). This study indicates that, despite decreased lung choline levels as a result of ingesting a lipotrophic diet, and unlike the liver, lung PC content is maintained at normal values. Although the lung total PC levels are maintained, there is a change in the partition of this lipid pool between the tissue and the alveolar space.
Exercise hyperthermia as a factor limiting physical performance: temperature effect on muscle metabolism
Authors: Kozlowski S. , Brzezinska Z. , Kruk B. , Kaciuba-Uscilko H. , Greenleaf J. E. , Nazar K.
Published: December 2017

The muscle contents of high-energy phosphates and their derivatives [ATP, ADP, AMP, creatine phosphate (CrP), and creatine], glycogen, some glycolytic intermediates, pyruvate, and lactate were compared in 11 dogs performing prolonged heavy exercise until exhaustion (at ambient temperature 20.0 +/- 1.0 degrees C) without and with trunk cooling using ice packs. Without cooling, dogs were able to run for 57 +/- 8 min, and their rectal (Tre) and muscle (Tm) temperatures increased to 41.8 +/- 0.2 and 43.0 +/- 0.2 degrees C, respectively. Compared with noncooling, duration of exercise with cooling was longer by approximately 45% while Tre and Tm at the time corresponding to the end of exercise without cooling were lower by 1.1 +/- 0.2 and 1.2 +/- 0.2 degrees C, respectively. The muscle contents of high-energy phosphates (ATP + CrP) decreased less, the rate of glycogen depletion was lower, and the increases in the contents of AMP, pyruvate, and lactate as well as in the muscle-to-blood lactate ratio were smaller. The muscle content of lactate was positively correlated with Tm. The data indicate that with higher body temperature equilibrium between high-energy phosphate breakdown and resynthesis was shifted to the lower values of ATP and CrP and glycolysis was accelerated. The results suggest that hyperthermia developing during prolonged muscular work exerts an adverse effect on muscle metabolism that may be relevant to limitation of endurance.
Bronchoconstriction in asthmatics exposed to sulfur dioxide during repeated exercise
Authors: Roger L. J. , Kehrl H. R. , Hazucha M. , Horstman D. H.
Published: December 2017

Young male volunteers with mild asthma and hypersensitivity to methacholine were exposed for 75 min with natural breathing to 0.0, 0.25, 0.5, and 1.0 ppm SO2. Each exposure included three 10-min periods of moderate treadmill exercise (minute ventilation 21 l . m-2 . min-1, O2 consumption 25 ml . kg-1, and heart rate 120/min). Specific airway resistance (sRaw) was not significantly increased after exercise in 0.25 ppm SO2, relative to the control exposure (clean air). In 0.5 and 1.0 ppm SO2, sRaw was increased twofold and threefold above preexposure levels, respectively, corresponding to increases of 3.2 and 9.2 cmH2O . s in excess over the increases seen in clean air (P less than 0.001). There was a broad range of responses to exercise and SO2. The increases in sRaw after the second and third exercises were significantly less than after the first exercise. Respiratory impedance measured by forced random noise suggests that the induced bronchoconstriction was primarily associated with peripheral airways. These results confirm that mild asthmatics selected for methacholine sensitivity have as a group significant bronchoconstriction in response to short-term moderate exercise with natural breathing in 1.0 and 0.5 ppm SO2. In addition, the induced bronchoconstriction is decreased after short-term repeated exercise in SO2.
Regulation of ventilation and oxygen consumption by delta- and mu-opioid receptor agonists
Authors: Schaeffer J. I. , Haddad G. G.
Published: December 2017

To study the effect of endorphins on metabolic rate and on the relationship between O2 consumption (VO2) and ventilation, we administered enkephalin analogues (relatively selective delta-receptor agonists) and a morphiceptin analogue (a highly selective mu-receptor agonist) intracisternally in nine unanesthetized chronically instrumented adult dogs. Both delta- and mu-agonists decreased VO2 by 40–60%. delta-Agonists induced a dose-dependent decrease in mean instantaneous minute ventilation (VT/TT) associated with periodic breathing. The decrease in VT/TT started and resolved prior to the decrease and returned to baseline of VO2, respectively. In contrast, the mu-agonists induced an increase in VT/TT associated with rapid shallow breathing. Arterial PCO2 increased and arterial PO2 decreased after both delta- and mu-agonists. Low doses of intracisternal naloxone (0.002–2.0 micrograms/kg) reversed the opioid effect on VT/TT but not on VO2; higher doses of naloxone (5–25 micrograms/kg) reversed both. Naloxone administered alone had no effect on VT/TT or VO2. These data suggest that 1) both delta- and mu-agonists induce alveolar hypoventilation despite a decrease in VO2, 2) this hypoventilation results from a decrease in VT/TT after delta-agonists but an increase in dead space ventilation after mu-agonists, and 3) endorphins do not modulate ventilation and metabolic rate tonically, but we speculate that they may do so in response to stressful stimulation.
Turnover of phospholipids isolated from fractions of lung lavage fluid
Authors: Baritussio A. , Carraro R. , Bellina L. , Rossi A. , Bruni R. , Pettenazzo A. , Enzi G.
Published: December 2017

To clarify the steps following surfactant secretion, we injected adult rabbits with radioactive palmitate, lavaged the airways, removed the cells, separated by ultracentrifugation lavage components into two fractions (B and C), and followed the labeling of phospholipids of these fractions. The results were compatible with the view that total and saturated phosphatidylcholine are transferred from B to C. Furthermore, the fluxes of total and saturated phosphatidylcholine through fraction C (0.45 and 0.30 mumol . h-1 . g lung-1, respectively) were compatible with the actual estimates of surfactant recycling. The labeling of phosphatidylglycerol ruled out a simple precursor-product relationship between B and C but was compatible with a nonideal first-order relationship. The labeling of phosphatidylinositol, cardiolipin, and phosphatidylethanolamine was incompatible with the existence of a direct precursor-product relationship between B and C. The labeling of total and saturated phosphatidylcholine suggests that fraction B may be made by active surfactant, whereas fraction C may contain surfactant modified for reuptake or for reuptake and catabolism.
Asymmetric [14C]albumin transport across bullfrog alveolar epithelium
Authors: Kim K. J. , LeBon T. R. , Shinbane J. S. , Crandall E. D.
Published: December 2017

Bullfrog lungs were prepared as planar sheets and bathed with Ringer solution in Ussing chambers. In the presence of a constant electrical gradient (20, 0, or -20 mV) across the tissue, 14C-labeled bovine serum albumin or inulin was instilled into the upstream reservoir and the rate of appearance of the tracer in the downstream reservoir was monitored. Two lungs from the same animal were used to determine any directional difference in tracer fluxes. An apparent permeability coefficient was estimated from a relationship between normalized downstream radioactivities and time. Results showed that the apparent permeability of albumin in the alveolar to pleural direction across the alveolar epithelial barrier is 2.3 X 10(-7) cm/s, significantly greater (P less than 0.0005) than that in the pleural to alveolar direction (5.3 X 10(-8) cm/s) when the tissue was short circuited. Permeability of inulin, on the other hand, did not show any directional dependence and averaged 3.1 X 10(-8) cm/s in both directions. There was no effect on radiotracer fluxes permeabilities of different electrical gradients across the tissue. Gel electrophoretograms and corresponding radiochromatograms suggest that the large and asymmetric isotope fluxes are not primarily due to digestion or degradation of labeled molecules. Inulin appears to traverse the alveolar epithelial barrier by simple diffusion through hydrated paracellular pathways. On the other hand, [14C]albumin crosses the alveolar epithelium more rapidly than would be expected by simple diffusion. These asymmetric and large tracer fluxes suggest that a specialized mechanism is present in alveolar epithelium that may be capable of helping to remove albumin from the alveolar space.
Effect of exercise training on antioxidant enzymes and cardiotoxicity of doxorubicin
Authors: Kanter M. M. , Hamlin R. L. , Unverferth D. V. , Davis H. W. , Merola A. J.
Published: December 2017

The purpose of this study was to correlate the exercise-induced changes of oxidant stress enzymes with possible modification of the response to the putative oxidant stressor doxorubicin. Enzymatic and histological changes were studied in mice placed on a 21-wk swim training program (1 h/day, 5 days/wk) with and without anthracycline administration. Doxorubicin (4 mg/kg) was administered intravenously through a tail vein on 10 separate days over a 7-wk period (twice weekly during weeks 10, 11, 14, 15, and 16). Blood, liver, and heart levels of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GP) were measured following the 9th and 21st wk. Myocardial histomorphological observations were made by light microscopy after 21 wk. Following 9 wk of training swim-trained animals had significantly elevated levels of CAT, SOD, and GP in blood, as well as elevated GP in liver. After 21 wk, trained animals, regardless of drug status, had elevated blood CAT and SOD activity and increased liver CAT and GP. Training also produced increases in blood GP, liver SOD, and heart CAT; however, in conjunction with doxorubicin these changes were not seen. The degree of cardiotoxicity was significantly greater in the sedentary drug-treated animals than in the swim-trained drug-treated animals. The results suggest a correlation between antioxidant enzyme levels in blood and liver and the degree of damage caused by an anthracycline drug. It was concluded that exercise ameliorates severe toxic damage caused by doxorubicin administration, possibly by increasing enzymes that combat free radical damage.
Effects of training on biochemical and functional properties of rodent neonatal heart
Authors: MacIntosh A. M. , Baldwin K. M. , Herrick R. E. , Mullin W. M.
Published: December 2017

This study was undertaken to determine biochemical and functional (in vivo) adaptations of the rodent neonatal heart in response to a training program of endurance running. Ten day-old rats were progressively trained on a treadmill (final intensity, 21 m/min, 30% grade, 1 h/day) until 75 days of age. The training program induced 14, 57, and 24% increases in relative heart mass, skeletal muscle citrate synthase activity, and whole-body maximal O2 uptake, respectively (P less than 0.05). Cardiac myosin (ATPase) and Ca2+-regulated myofibril ATPase were both reduced by approximately 15% in trained vs. sedentary animals (P less than 0.05). In the majority of trained hearts examined, the myosin isozyme profile reflected an estimated 14 +/- 3% shift toward the V3 or low ATPase isozyme. Left ventricular functional indices during submaximal exercise, derived from a fluid-filled indwelling cannula, indicated that the trained animals maintained similar left ventricular (LV) systolic pressure, LV + the time derivative of pressure, and systemic arterial mean blood pressure compared with their sedentary counterparts. These functional parameters were maintained even though the trained animals performed with lower submaximal exercise heart rate. These findings suggest that maximal exercise capacity can be enhanced in neonatal rats even though the biochemical potential for ATP degradation in the cardiac contractile system is lowered. We speculate that the trend to maintain the myosin isozyme pattern further in the direction of the V3 isozyme in the trained neonatal rat heart may reflect a means to economize cross-bridge cycling while maintaining normal levels of ventricle performance at a given submaximal work load.
Factors affecting tissue volume measurements in normal and edematous dog lungs
Authors: Huchon G. J. , Lipavsky A. , Pangburn P. , Hoeffel J. M. , Jibelian G. , Murray J. F.
Published: December 2017

To characterize further some of the factors affecting lung tissue soluble-gas rebreathing volume (Vlt), we determined the solubility of acetylene in blood and lung tissue, the influence of the presence of pulmonary edema on tissue solubility, the effects of varying tidal volume (VT), and the tissue volume actually measured in two groups of six anesthetized paralyzed dogs: controls (C) and oleic acid-induced pulmonary edema (OA). Each animal's solubility was used to compute Vlt for comparison with gravimetric lung weight (Ql) and extravascular lung water content (Qwl). Solubility at 37.5 degrees C in blood (0.125 ml X 100 ml-1 X Torr-1) exceeded that in lung tissue (P less than 0.005): C = 0.118 and OA = 0.112 ml X 100 ml-1 X Torr-1 (NS). Vlt, expressed as %Ql, increased with increasing VT (20, 35, and 50 ml/kg) in OA (62.2, 78.9, and 94.7%, respectively, P less than 0.0001) but not in C (92.4, 94.4, and 99.3%, respectively). We conclude that solubility differs in blood and lung tissue but not in normal and edematous lungs, Vlt is not affected by VT in normal dogs but is in those with pulmonary edema, and Vlt measures Ql rather than Qwl.
Sodium-amino acid cotransport by type II alveolar epithelial cells
Authors: Brown S. E. , Kim K. J. , Goodman B. E. , Wells J. R. , Crandall E. D.
Published: December 2017

Type II alveolar epithelial cell monolayers have been shown to actively transport sodium (Na+). Coupling to amino acid uptake could be an important mechanism for Na+ entry into these cells. This study demonstrates the presence of such a coupled cotransport mechanism in the plasma membrane of isolated type II cells by use of the nonmetabolizable amino acid analogue alpha-methylaminoisobutyric acid (MeAIB). Transport of MeAIB in 137 mM Na+ is saturable, with the uptake constant (Vmax) equaling 13.9 pmol X mg prot-1 X s-1 and the Michaelis-Menten constant (Km) equaling 0.13 mM. In the presence of Na+, MeAIB is accumulated against a concentration gradient. MeAIB uptake in the absence of Na+ is linear with MeAIB concentration, as expected for simple diffusion. The Hill coefficient for Na+-MeAIB cotransport is 1.11, suggesting a 1:1 stoichiometry. Proline inhibits Na+-MeAIB cotransport, with Ki equaling 0.5 mM. These findings suggest that Na+-amino acid cotransport may be an important pathway for Na+ (and/or amino acid) uptake into type II alveolar epithelial cells.
Electrode and cuvette for rapid continuous CO2 tension and pH measurement in blood
Authors: Katz S. A. , Roth A. C. , Feigl E. O.
Published: December 2017

An electrode and cuvette system has been developed for the continuous and rapid measurement of either blood CO2 tension or pH. The CO2 electrode consists of a 1.5-mm-diameter flat-tip glass pH electrode covered by a film of carbonic anhydrase solution, over which a 25-micron-thick dimethyl silicone membrane is attached. Porous ceramic filled with 20% polyacrylamide, equilibrated with a salt solution, serves as a salt bridge between a Ag-AgCl reference electrode and the pH electrode surface. The electrode is housed in a four-port cuvette assembly. Blood from a vessel of interest is delivered to the cuvette by means of an occlusive roller pump. The cuvette maintains the electrode and blood at a constant temperature and directs a continuous jet of blood against the electrode surface. The cuvette also allows for easy and frequent calibration of the electrode with either gas or liquid standards. The 90% response time of the CO2 electrode is 3.0 s for liquids and 1.3 s for gases. Removal of the dimethyl silicone membrane and carbonic anhydrase film yields a pH electrode that can continuously measure blood pH with a 90% response time of 1.6 s.