bluuebunny/crossref_metadata_2025 huggingface dataset:
Gas trapping in excised rabbit lungs depends on volume history and method of degassing
Authors: Hida W. , Lamm W. J. , Hildebrandt J.
Published: December 2017

Trapped gas volume (Vtg) was obtained after 5 and 10 repeated inflation-deflation cycles between transpulmonary pressure (Ptp) = 0 and 30 cmH2O in 12 experimental groups of freshly excised rabbit lungs. Gas flow rate was 1.0 ml/s except in one group (0.4 ml/s). In lungs degassed by O2 absorption (Dabs), Vtg increased from an initial 12–15% total lung capacity (TLC) (1st cycle) to 40% TLC (10th cycle), whereas in vacuum-degassed lungs (Dvac) the final Vtg was almost unchanged, remaining at less than 20% TLC. However, with the slower flow rate, Vtg in Dvac became 60% TLC. Increased lung water was not found in Dabs and therefore could not account for the above difference. In lungs not degassed after excision, Vtg increased roughly in proportion to the duration of passive collapse at Ptp = 0. However, a single brief exposure to a negative airway pressure (Pao = -10 cmH2O) resulted in a greater rate of increase of Vtg than 15-min collapse. When any of the foregoing groups were vacuum degassed after 5 cycles, they then resembled the Dvac group and showed almost no increase of Vtg in successive cycles. In Dvac, negative Pao and 15-min collapse had only minor effects on increasing Vtg. Thus, at a flow rate of 1 ml/s vacuum degassing almost eliminated all tendencies to trap gas in rabbit lungs, but the tendency was more than restored at slower flows. Brief airway closure by negative tracheal pressure can markedly enhance subsequent trapping of collapsed lungs. Differences arising from degassing methods might be due to effects on bronchomotor tone or on the physical characteristics of airway lining.
Thermoregulatory responses to exercise in dehydrated dogs
Authors: Baker M. A.
Published: December 2017

Measurements of rectal temperature (Tre), water lost by evaporation (Eresp) and drooling, cardiac output (CO), and common carotid blood flow (CCBF) were made in dogs (mean hydrated wt 31.0 +/- 1.5 kg) running for 1 h on a level treadmill at 7.5 km/h at an ambient temperature of 25 degrees C. Each animal was studied when it was hydrated ad libitum and when it had been dehydrated by removal of drinking water until 9–10% of the initial body weight had been lost. Dehydrated exercising animals had significantly higher Tre and lower rates of Eresp, CO, and CCBF. Tre and Eresp were measured in seven animals. Average Tre during running was 39.11 +/- 0.10 degrees C in hydrated and 39.80 +/- 0.25 degrees C in dehydrated animals (P less than 0.01). Average Eresp during running was 3.9 +/- 0.3 g/min in hydrated animals and 2.3 +/- 0.3 g/min in dehydrated animals (P less than 0.01). Average CO during exercise, measured in five animals, was 11.1 +/- 0.7 1/min in the hydrated state and 8.6 +/- 0.5 1/min in the dehydrated state (P less than 0.01). Unilateral CCBF during exercise, measured in four animals, was 602 +/- 40 ml/min in the hydrated state and 418 +/- 22 ml/min in the dehydrated state (P less than 0.01). Water lost by drooling in seven exercising animals was 41.5 +/- 11 g/h when they were hydrated and 0.6 +/- 0.4 g/h when they were dehydrated. It is concluded that dehydrated dogs doing mild exercise can save water by reducing Eresp and regulating body temperature above hydrated levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Maximum coronary blood flow and minimum coronary resistance in exercise-trained dogs
Authors: Liang I. Y. , Hamra M. , Stone H. L.
Published: December 2017

Exercise training has been found to increase coronary vascularity of the heart in experimental animals. Maximum coronary flow and minimum coronary resistance were determined in 16 dogs with the injection of microspheres (15 micron) into the left atrium at rest and during the intravenous infusion of adenosine (0.7 mg X min-1 X kg-1). Heart rate was paced at 150 beats/min. Dogs were divided into three groups with microsphere injections made before and after 4–5 wk of daily exercise (group 1); before and after 8–10 wk of daily exercise (group II); and before and after 8–10 wk of cage rest (group III). Results of average left ventricular maximum myocardial flow before and after daily exercise were 4.08 +/- 0.34 and 4.89 +/- 0.33 ml X min-1 X g-1 for group I, 5.13 +/- 0.32 and 5.55 +/- 0.56 ml X min-1 X g-1 for group II, and 5.24 +/- 0.43 and 4.34 +/- 0.55 ml X min-1 X g-1 for group III. Arterial pressure, maximum coronary flow, and minimum coronary resistance were not significantly different before and after any condition in all three groups of dogs. Peak reactive hyperemia coronary flow was not altered by daily exercise. These results indicate that maximum coronary flow and minimum coronary resistance were not altered by either 4–5 or 8–10 wk of exercise training.
Alveolar ventilation during high-frequency oscillation: core dead space concept
Authors: Isabey D. , Harf A. , Chang H. K.
Published: December 2017

To assess the role of direct alveolar ventilation during high-frequency ventilation, we studied convective gas mixing during high-frequency oscillation with tidal volumes close to the dead space volume in a simple physical model. A main conduit representing a large airway was connected with a rigid sphere (V = 77, 517, and 1,719 cm3) by a small circular tube (d = 0.3 and 0.5 cm; L = 5, 10, and 20 cm). The efficiency of sinusoidal oscillations (f = 5, 20, and 40 Hz) applied at one end of the main conduit was assessed from the washout of a CO2 mixture from the sphere; to flush CO2 from the main fluid line, a constant flow of air was used. The decay in CO2 concentration measured in the sphere was exponential and therefore characterized by a measured time constant (tau m). Taking the small tube volume as the ventilatory dead space (VD), an effective tidal volume (VT*) was computed from tau m and compared with the tidal volume (VT) obtained separately from the pressure variation in the sphere. The discrepancy between these two tidal volumes has been found to be uniquely dependent on the ratio VT/VD within the range of VT/VD studied (0.5–2.2). For VT/VD less than 1.2, VT* was larger than VT, indicating that the conventional concept of alveolar ventilation does not apply. From the partition of the oscillatory flow in the small tube into two regions, the core and the unsteady boundary layer, we theoretically computed the proportions of the sinusoidal flow (or tidal volume) and the dead space for each region.(ABSTRACT TRUNCATED AT 250 WORDS)
Site of deposition and factors affecting clearance of aerosolized solute from canine lungs
Authors: Rizk N. W. , Luce J. M. , Hoeffel J. M. , Price D. C. , Murray J. F.
Published: December 2017

We determined the influence of several factors on lung solute clearance using aerosolized 99mTc-diethylenetriaminepentaacetate. We used a jet nebulizer-plate separator-balloon system to generate particles with an activity median aerodynamic diameter of 1.1 micron, administered the aerosol in a standard fashion, and determined clearance half times (t1/2) with a gamma-scintillation camera. The following serial studies were performed in five anesthetized, paralyzed, intubated, mechanically ventilated dogs: 1) control, with ventilatory frequency (f) = 15 breaths/min and tidal volume (VT) = 15 ml/kg during solute clearance; 2) repeat control, for reproducibility; 3) increased frequency, with f = 25 breaths/min and VT = 10 ml/kg; 4) positive end-expiratory pressure (PEEP) of 10 cmH2O; 5) unilateral pulmonary arterial occlusion (PAO); and 6) bronchial arterial occlusion (BAO). Control t1/2 was 25 +/- 5 min and did not change in the repeat control, increased frequency, or BAO experiments. PEEP markedly decreased t1/2 to 13 +/- 3 min (P less than 0.01), and PAO increased it to 37 +/- 6 min (P less than 0.05). We conclude that clearance from the lungs by our method is uninfluenced by increased frequency, increases markedly with PEEP, and depends on pulmonary, not bronchial, blood flow.
Nasal and laryngeal reflex responses to negative upper airway pressure
Authors: van Lunteren E. , Van de Graaff W. B. , Parker D. M. , Mitra J. , Haxhiu M. A. , Strohl K. P. , Cherniack N. S.
Published: December 2017

The effects of negative pressure applied to just the upper airway on nasal and laryngeal muscle activity were studied in 14 spontaneously breathing anesthetized dogs. Moving average electromyograms were recorded from the alae nasi (AN) and posterior cricoarytenoid (PCA) muscles and compared with those of the genioglossus (GG) and diaphragm. The duration of inspiration and the length of inspiratory activity of all upper airway muscles was increased in a graded manner proportional to the amount of negative pressure applied. Phasic activation of upper airway muscles preceded inspiratory activity of the diaphragm under control conditions; upper airway negative pressure increased this amount of preactivation. Peak diaphragm activity was unchanged with negative pressure, although the rate of rise of muscle activity decreased. The average increases in peak upper airway muscle activity in response to all levels of negative pressure were 18 +/- 4% for the AN, 27 +/- 7% for the PCA, and 122 +/- 31% for the GG (P less than 0.001). Rates of rise of AN and PCA electrical activity increased at higher levels of negative pressure. Nasal negative pressure affected the AN more than the PCA, while laryngeal negative pressure had the opposite effect. The effects of nasal negative pressure could be abolished by topical anesthesia of the nasal passages, while the effects of laryngeal negative pressure could be abolished by either topical anesthesia of the larynx or section of the superior laryngeal nerve. Electrical stimulation of the superior laryngeal nerve caused depression of AN and PCA activity, and hence does not reproduce the effects of negative pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Identification of medullary loci critical for neurogenesis of gasping
Authors: St John W. M. , Bledsoe T. A. , Sokol H. W.
Published: December 2017

We hypothesized that a discrete medullary locus, critical for gasping neurogenesis, could be identified. In decerebrate, cerebellectomized, vagotomized, paralyzed, and ventilated cats, activities of phrenic, hypoglossal, and recurrent laryngeal nerves were monitored. Gasping was induced by freezing the brain stem, via a fork thermode, at the pontomedullary junction. By reversible cooling of the medulla, chemical lesions with kainic acid, and radio-frequency lesions, a critical area for gasping neurogenesis was localized bilaterally 2–3 mm rostral to obex, 2.0–2.5 mm lateral to midline, and 3–4 mm ventral to medullary surface. Electrical stimulation in this area elicited premature gasps, whereas unilateral lesions or lidocaine injections eliminated gasping activities in all nerves. These procedures did not cause similar changes during eupnea. In apneusis, however, lidocaine injections markedly altered the pattern or caused apnea. We conclude that discharge of neurons in a discrete portion of the lateral tegmental field of medulla is required for gasping neurogenesis. Our results are consistent with these neurons comprising the central pattern generator for gasping.
CO2 rebreathing and exercise ventilatory responses in humans
Authors: Menitove S. M. , Rapoport D. M. , Epstein H. , Sorkin B. , Goldring R. M.
Published: December 2017

The relationship between the resting response to CO2 rebreathing and the ventilatory response to CO2 production during exercise was examined in 20 healthy untrained male subjects and in six patients with obesity hypoventilation syndrome. Patients were chosen because of a severely reduced response to CO2 rebreathing. There was no correlation between the CO2 rebreathing response and the exercise ventilatory response in the normal subjects, the patients, or in the group considered as a whole. This lack of correlation could not be accounted for by differences in ventilatory and occlusion pressure responses nor by reporting responses as a function of a change in hydrogen ion concentration. The independence of the CO2 rebreathing response and the exercise ventilatory response suggests the CO2 rebreathing response does not measure the relevant parameters of ventilatory control during exercise.
Breathing pattern during induced bronchoconstriction
Authors: Chadha T. S. , Schneider A. W. , Birch S. , Jenouri G. , Sackner M. A.
Published: December 2017

The breathing patterns of normal subjects monitored with respiratory inductive plethysmography were investigated after mild increases in respiratory resistance provoked by aerosolized methacholine during natural breathing and while breathing on a mouthpiece to a pneumotachograph. First, during natural breathing, comparisons of inspiratory ventilation (VI), tidal volume (VT), frequency (f), inspiratory time (TI), fractional inspiratory time (TI/TT), and mean inspiratory flow (VT/TI) were made before and after aerosolized buffered saline and methacholine in a dose that reduced specific airway conductance (sGaw) by 35% (PD35). There was a significant increase in VT/TI and VI after methacholine, whereas VT, f, TI, and TI/TT were not consistently modified by saline or methacholine. Pretreatment with bronchodilators prevented changes in respiratory resistance (Rrs) as well as in breathing pattern after PD35 methacholine. On another day, Rrs, end-expiratory lung volume level, and breathing pattern during natural breathing were monitored after administration of predetermined doses of methacholine that reduced sGaw by 25% (PD25), PD35, and 55% (PD55). Increases in VT/TI and end-expiratory lung volume level paralleled the increases in Rrs after each dose of methacholine but not with saline control. VI increased along with Rrs at the PD25 and PD35 doses but plateaued at the PD55 dose while Rrs continued to rise. There were no changes in breathing pattern in subjects who breathed on a mouthpiece to a pneumotachograph after PD55 methacholine. Thus alterations of the breathing pattern due to mild-to-moderate degrees of bronchoconstriction are characterized by progressive rises of mean inspiratory flow (an index of respiratory center drive) and end-expiratory lung volume level (a measure of pulmonary hyperinflation), but VI plateaus at the more severe degree of bronchoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)
Adaptations of quadriplegic men to consecutively loaded breaths
Authors: Axen K.
Published: December 2017

Ventilatory responses to graded elastic and resistive loads from 20 quadriplegic men were analyzed. During the 1st, 5th, and 10th consecutively loaded inspirations 1) responses from different subjects ranged from a weak tidal volume defense coupled with an increased breathing frequency to a strong tidal volume defense coupled with a decreased frequency; 2) strong tidal volume defenders generally employed longer inspirations than did weak tidal volume defenders; and 3) individual respiratory frequencies were mediated by similar changes in inspiratory and/or expiratory timing. Thus the group response was qualitatively similar on the 1st, 5th, and 10th loaded breaths. Quantitatively, however, minute ventilation increased throughout each 10-breath episode due to progressively larger tidal volumes coupled with equal breathing frequencies. These larger tidal volumes were due to progressively stronger inspirations with no changes in timing during elastic loading, whereas they were due to both stronger and longer inspirations during resistive loading. These findings, which are qualitatively the same as those found in healthy subjects, indicate that sensory input from the mouth, lung, and diaphragm, and motor output to the diaphragm and accessory muscles are sufficient, by themselves, to mediate normal patterns of ventilatory adjustments during consecutively loaded breaths.
Computer processing of phrenic neurograms
Authors: Bryant H. J. , Abbrecht P. H.
Published: December 2017

Manual processing of large numbers of electrophysiological waveforms is a tedious process prone to subjective errors in judgment. To eliminate these problems, we developed computer algorithms and techniques to analyze cat phrenic neurograms produced in response to step changes in end-tidal PCO2. The computer analyzed the neurogram in terms of a model waveform, which consisted of 1) base-line activity made up primarily of noise, 2) an initial sharp increase from base line, 3) a slower ramplike increase in activity, 4) a peak value, and 5) a rapid decrease in activity back to base line. Parameters describing these model elements as well as inspiratory and expiratory times were calculated by the computer. Computer-produced parameters were compared with manually calculated parameters from chart recordings for over 200 individual neurograms. Repeated manual processing of the neurogram had a variability of +/- 10% in the parameter estimates. The computer-produced parameters fell within this range more than 89% of the time. Although the techniques described are directed specifically toward phrenic neurogram analysis, the methods are general enough to be useful in computer processing of other types of physiological waveforms.
An analysis of the mechanism by which gamma-aminobutyric acid depresses ventilation in the rat
Authors: Hedner J. , Hedner T. , Wessberg P. , Jonason J.
Published: December 2017

Intracerebroventricular administration of gamma-aminobutyric acid (GABA) or intraperitoneal injection of the GABA transaminase A inhibitor aminooxyacetic acid (AOAA) depressed ventilation in halothane-anesthetized rats. The depression was due to changes in both respiratory frequency (f) and tidal volume (VT) after GABA, whereas AOAA decreased only f. Intracerebroventricular GABA decreased inspiratory drive (VT/TI; intrapulmonary pressure at 100 ms) but did not change the bulbopontine setting of inspiratory duration (TI). Moreover, respiratory duty cycle (TI/TT) was decreased, and the ventilatory response to CO2 exposure was blunted. The ventilatory depression induced by GABA was reversed by the GABA antagonist bicuculline. The GABA content measured 45 min after AOAA administration was significantly increased in the whole brain, the hemispheres, striatum, and lower spinal cord regions. Whole-brain GABA content was significantly correlated to the changes in f, minute ventilation, TI, expiratory duration (TE), and total cycle duration. Furthermore, there was a significant negative correlation between brain stem GABA content and TI/TT but not VT/TI. In summary, GABA seems to interact with the central regulation of respiration at different levels in the brain. The main effect of increased endogenous concentrations of GABA is, however, a decrease in respiratory frequency due to a prolongation in TE.
Effect of mild essential hypertension on control of forearm blood flow during exercise in the heat
Authors: Kenney W. L. , Kamon E. , Buskirk E. R.
Published: December 2017

Six essential hypertensive (resting mean arterial pressure, MAP greater than 110 mmHg) and eight normotensive (resting MAP less than 95 mmHg) men, aged 30–58 yr, were tested during 1 h of dynamic leg exercise in the heat. Environmental conditions were fixed at 38 degrees C dry-bulb temperature and 28 degrees C wet-bulb temperature; exercise intensity was preset to approximate 40% of each subject's maximal aerobic capacity (actual range 38–43%). Forearm blood flow (FBF) was measured by impedance plethysmography. The intergroup difference in arterial pressure was maintained but not increased or decreased during exercise in the heat. FBF increased in both groups, but the increase was significantly less for the hypertensive subjects. FBF showed a significant linear correlation (different from 0) with core temperature in seven of eight control subjects but in none of the hypertensive subjects. The magnitude of FBF increase was inversely proportional to resting MAP (r = -0.89). It was concluded that essential hypertensive subjects respond to exercise in the heat with a diminished FBF response related to an alteration in control relative to central (core temperature) influences. This may be due to an imbalance between thermal and nonthermal (baroreflex) mechanisms controlling cutaneous blood flow.
Lung fluid balance, vascular permeability, and gas exchange after acid aspiration in awake goats
Authors: Winn R. , Stothert J. , Nadir B. , Hildebrandt J.
Published: December 2017

Lung injuries were produced by instilling 2.5 ml/kg of 0.1 N HCl into the trachea of lightly anesthetized goats with previously implanted lung lymph fistulas. Lymph flow (QL), lymph-to-plasma protein concentration ratio (L/P), pulmonary arterial and wedge pressures (Ppa, Pw), percent shunt (Qs/QT), and postmortem extravascular lung water (EVLW) were then measured for up to 48 h. QL began to increase within 15 min of injury from a baseline value of 7.2 ml/h to reach a peak of 231% of base line by 1.5 h, then decreased to 160% at 24 h and returned to base line by 48 h. Average L/P increased from 0.66 to a peak of 0.73 at 2 h. Ppa increased from 17.0 cmH2O to a first peak of 25.3 cmH2O at 15 min, then decreased to base line by 75 min. There was a second rise that peaked at 3 h before returning to base line at 24–48 h; Pw was unchanged throughout. Qs/QT increased from 8.5 to a peak of 34% at 1 h, then decreased to 15% at 4 h, and stabilized at 17–20% at 48 h. EVLW was 237% of base line at 4 h and declined somewhat but remained elevated at 194% of base line at 24 and 48 h. Qs/QT was less than expected based on the reduction in lung volume after aspiration. We conclude that microvascular permeability was increased after acid and that a protective vasoconstriction, probably due to local hypoxia, directed blood away from nonventilated alveoli.
Cyclooxygenase inhibition during phorbol-induced granulocyte stimulation in awake sheep
Authors: Newman J. H. , Loyd J. E. , Ogletree M. L. , Meyrick B. O. , Brigham K. L.
Published: December 2017

In vitro, phorbol myristate acetate (PMA) causes sheep granulocytes to release superoxide. Infused into sheep, PMA causes leukopenia, hypoxemia, pulmonary hypertension, and increased flow of protein-rich lung lymph. Lung lymph thromboxane B2 and 6-ketoprostaglandin F1 alpha levels rise markedly after PMA infusion. To see whether cyclooxygenase products of arachidonic acid mediate the lung vascular responses to PMA, we infused 5 micrograms/kg PMA twice in each of six sheep, once in the presence of sodium meclofenamate and once alone. We varied the order of paired experiments and allowed 4–7 days between experiments. Meclofenamate (5 mg/kg loading dose + 3 mg X kg-1 X h-1 infusion) given alone had no effect on base-line variables. Meclofenamate inhibited or delayed the initial pulmonary hypertension and hypoxemia after PMA but exaggerated the later increase in pulmonary arterial pressure; it prevented any increase in thromboxane B2 and 6-ketoprostaglandin F1 alpha after PMA. Meclofenamate did not affect the degree of leukopenia or the severity of the later hypoxemia nor did it prevent accumulation of granulocytes in the lung. Lung lymph flow was higher with meclofenamate + PMA than with PMA alone, but lymph-to-plasma protein concentration ratio was lower, suggesting that the main effect of meclofenamate on lymph production after PMA was related to the degree of pulmonary hypertension. We conclude that the early increase in pulmonary arterial pressure caused by PMA is mediated by a cyclooxygenase product of arachidonic acid, possibly thromboxane A2, but the later pulmonary hypertension and the increase in pulmonary vascular permeability are not the result of cyclooxygenase products.
Effect on arterial pressure of rhythmically contracting the hindlimb muscles of cats
Authors: Kaufman M. P. , Rybicki K. J. , Waldrop T. G. , Mitchell J. H.
Published: December 2017

Although static contraction of the hindlimb muscles of anesthetized cats is known to reflexly increase arterial pressure and heart rate, the cardiovascular effects of rhythmic contractions of these muscles is unclear. To help clarify this issue, we determined, in chloralose-anesthetized cats, the effects on arterial pressure and heart rate of rhythmically contracting the hindlimb muscles at a frequency of 5 Hz. In addition, we determined the effect of rhythmic contractions on the impulse activity of group III and IV muscle afferents whose activation is known to increase cardiovascular function. We found that rhythmic contractions increased arterial pressure (from 108 +/- 8 to 134 +/- 9 mmHg; P less than 0.05) and heart rate (from 192 +/- 13 to 208 +/- 10 beats/min; P less than 0.05) in 10 cats and decreased arterial pressure (from 107 +/- 8 to 93 +/- 9 mmHg; P less than 0.05) but did not change heart rate in 9 other cats. The increases were reflex, because they were prevented by cutting the spinal roots innervating the contracting hindlimb. The decreases, however, were not reflex, because they persisted after spinal root section. The differences in the arterial pressure responses to rhythmic contractions may have been partly due to individual differences in the level of anesthesia, because in three cats the pressor responses to this maneuver were converted to depressor responses after giving the cats additional chloralose. Rhythmic contractions of the triceps surae muscles stimulated 8 of 10 group III afferents and 9 of 16 group IV afferents. We conclude that rhythmic contraction is capable of reflexly increasing cardiovascular function in cats provided that the effect is not depressed by anesthesia.
Neuromuscular response to resistive unloading: helium vs. bronchodilation
Authors: DeWeese E. L. , Sullivan T. Y. , Yu P. L.
Published: December 2017

To evaluate the neuromuscular response to resistive unloading, we compared the ventilatory and occlusion pressure (P100) response of normal subjects breathing 20.9% O2 in helium (He-O2) with their response to unloading produced by inhaled atropine sulfate. During He-O2 breathing airway resistance (Raw) fell by 49% of the base-line value on air, and P100 decreased by 20.8%. Minute ventilation, tidal volume, respiratory frequency, end-tidal Pco2, inspiratory and expiratory duration, and mean inspiratory flow were not significantly different when air was replaced by He-O2. In contrast, although atropine reduced Raw by an equivalent amount, there was no change in P100. Atropine had no significant effect on other respiratory variables, although a trend toward higher minute ventilation was noted. Fowler dead space increased after atropine but was not affected by He-O2. We conclude that, unlike He-O2 unloading, atropine unloading does not cause a reduction in occlusion pressure. This may be due to the effect of atropine on anatomical dead space which stimulates ventilation sufficiently to offset the fall in neuromuscular output due to resistive unloading.
Mechanism of hyperpnea induced by changes in pulmonary blood flow
Authors: Green J. F. , Schmidt N. D.
Published: December 2017

Increases in pulmonary blood flow can elicit hyperpnea. To examine the mechanisms responsible, we surgically isolated the systemic and pulmonary circulations in six dogs and independently controlled PCO2, PO2, and blood flow in each circuit. Anesthesia was induced with ketamine and maintained with halothane. Systemic venous return was drained from the right atrium and passed through a membrane oxygenator and heat exchanger; blood was returned to the ascending aorta (Qs). An identical bypass was established for the pulmonary circulation, draining blood from the left atrium and returning it to the pulmonary artery (Qp). The lungs were initially ventilated with room air. Qs and systemic arterial CO2 gas tension were maintained at approximately 0.080 1 X min-1 X kg-1 and 40 Torr, respectively. Pulmonary arterial CO2 gas tension was set near 55 Torr, and Qp varied. Ventilatory drive was assessed by minute integration (MI) of the activity recorded from the central end of the left C5 root of the phrenic nerve. MI increased as much as 160% above control as Qp was increased over the range of 0.025 (control) to 0.175 1 X min-1 X kg-1. When pulmonary CO2 gradients were eliminated by a rebreathing technique, MI was independent of Qp. These results suggest that CO2-sensitive pulmonary receptors respond to the change in pulmonary PCO2 gradients which occur when Qp is elevated (breathing room air) augmenting ventilation.
Effects of hypoxia on ventilation during postnatal development in conscious kittens
Authors: Bonora M. , Marlot D. , Gautier H. , Duron B.
Published: December 2017

Effects of steady-state hypoxia (inspired O2 fraction = 0.11) on ventilation and breathing pattern were studied during postnatal development in unanesthetized kittens. Studies were done from 2 days to 8 mo of age, every week during the first month and every month thereafter. During the first 2 months, states of consciousness were determined. In the first month, minute ventilation (VE) was depressed in hypoxia compared with control values in air, whereas in the older kittens VE was increased in hypoxia, as in adult cats. The inhibitory effect of hypoxia was observed in all three states of consciousness in 7- and 14-day-old kittens. In the 21- and 28-day-old kittens, VE could not be reliably related to the state of consciousness. In the 2-mo-old kittens, VE increased in all states. Tidal volume (VT) was markedly decreased in kittens up to 14 days of age, and respiratory frequency increased. In the 21- and 28-day-old kittens, changes in breathing pattern were variable. In the oldest, the increase of VE was mainly due to an increase of VT. We conclude that in unanesthetized kittens, the ventilatory response to hypoxia is mature at 2 mo of age. The hypoxic tachypnea observed at 7 and 14 days resembles that previously seen in adult carotid-denervated cats, and may be due to a low level of carotid chemoreceptor drive and to a central excitatory effect of hypoxia on respiratory frequency. The complex response observed during the first month of life must reflect the development of peripheral and central mechanisms and their interactions.
Mechanical arrangement of costal and crural diaphragms in dogs
Authors: Decramer M. , De Troyer A. , Kelly S. , Macklem P. T.
Published: December 2017

To assess the mechanical arrangement of the costal and crural parts of the diaphragm, we studied changes in diaphragmatic length with piezoelectric crystals in 17 supine anesthetized dogs. During control resting inspiration, the crural part usually shortened more and earlier than the costal part. After phrenicotomy, the crural part always lengthened during inspiration, whereas the costal part shortened or lengthened. These interanimal differences disappeared after opening of the abdomen; the costal part then always lengthened during inspiration. During stimulation of one part, the relaxed nonstimulated part always lengthened. However, when compared with the relationship between length and transdiaphragmatic pressure (Pdi) obtained during passive deflation, the lengthening of the relaxed part during stimulation of either part was small. This difference between predicted and measured Pdi-length relationship decreased in magnitude as lung volume increased above functional residual capacity (FRC) and increased as residual volume was approached. These results indicate that 1) even during quiet breathing the diaphragm in the dog is not a single functional entity; 2) at FRC the costal and crural portions of the diaphragm behave as if they were mechanically arranged partly in parallel and partly in series; and 3) they gradually move into a pure mechanical series arrangement as lung volume increases.
Induction of airway collapse with subatmospheric pressure in awake patients with sleep apnea
Authors: Suratt P. M. , Wilhoit S. C. , Cooper K.
Published: December 2017

To determine whether the pharyngeal airway is abnormal in awake patients with obstructive sleep apnea (OSA), we measured the ability of the pharyngeal airway to resist collapse from subatmospheric pressure applied to the nose in awake subjects, 12 with OSA and 12 controls. Subatmospheric pressure was applied to subjects placed in the supine position through a tightly fitting face mask. We measured airflow at the mask as well as mask, pharyngeal, and esophageal pressures. Ten patients developed airway obstruction when subatmospheric pressures between 17 and 40 cmH2O were applied. Obstruction did not occur in two patients with the least OSA. Obstruction did not occur in 10 controls; one obese control subject developed partial airway obstruction when -52 cmH2O was applied as did another with -41 cmH2O. We conclude that patients with significant OSA have an abnormal airway while they are awake andthat application of subatmospheric pressure may be a useful screening test to detect OSA.
Effects of intense exercise training on plasma catecholamines in coronary patients
Authors: Ehsani Ali A. , Heath Gregory W. , Martin Wade H. , Hagberg James M. , Holloszy John O.
Published: December 2017

This paper reports the effect of 12 mo of intense endurance exercise training on the plasma catecholamine response to exercise in 11 male patients [aged 50 ± 8 yr (mean ± SD)] with coronary artery disease. A substantial adaptation to training was attained as evidenced by a 42% increase in maximum O2uptake capacity. At rest, heart rate was lower after training, but resting blood pressure and plasma catecholamines were unchanged. At the same absolute work rate, plasma norepinephrine and epinephrine levels, rate pressure product, and ischemic S-T segment depression were all significantly lower aftertraining. A higher plasma norepinephrine level was attained at maximal exercise after training (2,049± 654 before vs. 3,408 ± 1,454 pg/ml after, P < 0.025); this was associated with a higher systolic blood pressure (175 ± 25 before vs. 188 ± 22 mmHg after, P < 0.025) and a higher rate-pressure product (25.3 x 103 ± 4.5 x 103 before vs. 27.6 x 103 ± 5.2 x 103 after, P < 0.025). Despite the higher plasma norepinephrine level and rate pressure product, S-T segment depression at maximal exercise was unchanged. These findings suggest that some patients with coronary arterial disease can attain a higher myocardial O2 requirement, without electrocardiographic evidence of increased ischemia, after prolonged strenuous exercise training.

myocardial infarction; coronary arterial disease

Submitted on July 5, 1983

Submitted on July 5, 1983
High-frequency ventilation: lymph flow, lymph protein flux, and lung water
Authors: Martin D. , Rehder K. , Parker J. C. , Taylor A. E.
Published: December 2017

The effects of high-frequency oscillatory (HFV) ventilation on lung fluid balance and microvascular permeability to macromolecules were measured in open-chest dog lungs. Prenodal lung lymph flow, concentration of total plasma proteins in lymph and plasma, pulmonary arterial and left atrial pressure,cardiac output, and blood-free lung wet-to-dry weight ratios were measured for conventional mechanical ventilation (CMV, 12/min, 200–300 ml tidal volume) and HFV of 15 Hz and a stroke volume of 40–50 ml for normal and elevated left atrial pressures. HFV increased both lymph flow and lung water (68 and 20%, respectively), and lymph-to-plasma ratios of total plasma proteins remained unchanged. When left atrial pressure was increased, an analysis of lymph protein flux indicates that the lung microvascular permeability was not altered by HFV. The increase in lymph flow and lung water associated with HFV may reflect an increased microvascular exchange surface area or a change in interstitial fluid pressure.
Effect of regional inhomogeneity on collateral airway resistance
Authors: Fuller S. D. , Robinson N. E.
Published: December 2017

We studied the interaction of transpulmonary pressure (Pao) and the pressure in an isolated sublobar lung segment (Ps) on collateral resistance (Rcoll) in excised dog lungs. A double-lumen catheter was advanced through the trachea and wedged in a peripheral airway. Gas flowed through the outer lumenof the catheter (Vcoll) to enter the segment while Ps was measured by the inner lumen. Collateral resistance was calculated as Rcoll = (Ps - Pao)/Vcoll. At constant Ps, raising Pao sharply decreased Rcoll, but at constant Pao, raising Ps increased Rcoll. Replotting these data showed that Rcoll was related to the pressure difference between the segment and the remainder of the lobe (Ps - Pao), such that raising Ps - Pao caused no change in Rcoll at lower Pao but increased Rcoll at higher Pao. Similarfindings occurred in the lungs of closed-chest anesthetized dogs. We propose that this technique measures the sum of resistances of airways and collateral channels found in the segment body (Rs) and of those passing through the segment-lobar parenchymal interface (Ri). Raising Ps - Pao decreases Rs because of the volume dependency of airway resistance and increases Ri due to tissue distortion at the interface occurring as a result of inhomogeneous segment inflation. The net change in measured Rcoll depends on which of its components change in greatest magnitude. This effect varies with Pao due to thehyperbolic relationship of Pao with airway and collateral resistance.
August and Marie Krogh and respiratory physiology
Authors: Schmidt-Nielsen B.
Published: December 2017

August and Marie Krogh first met in 1904 in the laboratory of Christian Bohr, a well-known Danish physiologist, where August was a teaching assistant and Marie Jorgensen a medical student. August, the oldest son of a brewer in Grenaa, Denmark, had recently obtained his doctorate for his work on respiration in frogs. Marie Jorgensen, the daughter of a farmer in Fyn, had at the age of six decided to pursue a medical career. August and Marie were married in 1905, and she joined him in some of his research. Christian Bohr was a staunch proponent of the theory that O2 was secreted across the lung epithelium. August Krogh at first set out to prove this hypothesis through precise and accurate measurements of gases in arterial blood and alveolar air with new apparatus he had constructed. Marie joined in this work, but the results they obtained did not support Bohr's hypothesis; to the contrary a series of very careful studies definitively proved that O2 is transported across the alveolar epithelium by diffusion alone. Due to the conflict with Bohr's views they delayed publication of the results until 1910. Marie Krogh, who finished her medical degree in 1907 and had begun a family, undertook an investigation of CO diffusion capacity through human lungs. This was to test if the rate of O2 diffusion was sufficient to account for the O2 uptake even at high altitudes or during various pulmonary diseases. Thirty-five years later the CO method, as described by Marie Krogh, was rediscovered and is now used extensively as a clinical test. August, in his continued studies of respiration in animals and humans, became interested in the delivery of O2 from the capillaries to the tissue. The studies that followed led to his discovery of the regulation of capillary circulation, for which he was awarded the Nobel Prize in 1920.
Altering hydrodynamic variables influences PGI2 production by isolated lungs and endothelial cells
Authors: van Grondelle A. , Worthen G. S. , Ellis D. , Mathias M. M. , Murphy R. C. , Strife R. J. , Reeves J. T. , Voelkel N. F.
Published: December 2017

Because deformation of lung tissue stimulates prostaglandin synthesis, we wanted to investigate whether hydrodynamic forces would affect lung prostacyclin (PGI2) production. To test the hypothesis that lung prostacyclin synthesis was flow dependent, we examined lung prostacyclin production after flow alterations. Using a salt solution that contained either Ficoll or albumin as a perfusate, we changed the flow to half and to double the control flow. When flow was changed, lung prostacyclin production followed changes in flow and pressure drop. When flow was varied in lungs treated with indomethacin, prostacyclin production was too low to be measurable. Variations in pressure pulsatility at constant mean flow had no influence on lung prostacyclin production. Since vascular distension may also stimulate prostacyclin production, we increased venous pressure. An increase in venous pressure (from 2.1 to 4.8 mmHg) had no effect on prostacyclin production; a further increase in venous pressure (to 7.5 mmHg) initiated edema and caused a large increase in prostacyclin production. When we subjected monolayers of endothelial cells cultured in wells to defined shear rates, the prostacyclin concentration in the supernatant quickly increased to a maximum. The absence of further increase with greater shear may have reflected feedback control of prostacyclin synthesis. The results indicated that hydrodynamic disturbances affect endothelial cells and stimulate arachidonate metabolism. Lung prostacyclin production may be related to flow. However, this effect is small compared with the lung prostacyclin production during edema formation.
Morphological and physiological responses of the lungs of dogs to acute decompression
Authors: Catron P. W. , Flynn E. T. , Yaffe L. , Bradley M. E. , Thomas L. B. , Hinman D. , Survanshi S. , Johnson J. T. , Harrington J.
Published: December 2017

The lung–s response to decompression was studied in dogs anesthetized with pentobarbital sodium. Arterial pressure, hematocrit, right ventricular pressure, left ventricular end-diastolic pressure (LVEDP), dynamic compliance (CL), pulmonary resistance (RL), and arterial PO2, PCO2, and pH were measured prior to and for 3 h after a simulated air dive to 300 feet of seawater. Bronchoscopy was performed predive and at 3 h postdive. At 3 h animals were killed, and sections of lung were excised for histological examination. The decompression profile used regularly produced pulmonary hypertension, systemic hypotension, hemoconcentration, and arterial hypoxemia. CL fell in all but one dived animal. RL was more variable but remained unchanged postdive in most animals. The decompression stress did not alter the bronchoscopic and histological appearance of the airway mucosa. Pulmonary edema was regularly observed in histological sections and occurred without elevations of LVEDP. We concluded that noncardiac pulmonary edema is the principal response of the lung to decompression stress.
Measurement and theory of wheezing breath sounds
Authors: Gavriely N. , Palti Y. , Alroy G. , Grotberg J. B.
Published: December 2017

We measured the time and frequency domain characteristics of breath sounds in seven asthmatic and three nonasthmatic wheezing patients. The power spectra of the wheezes were evaluated for frequency, amplitude, and timing of peaks of power and for the presence of an exponential decay of power with increasing frequency. Such decay is typical of normal vesicular breath sounds. Two patients who had the most severe asthma had no exponential decay pattern in their spectra. Other asthmatic patients had exponential patterns in some of their analyzed sound segments, with a range of slopes of the log power vs. log frequency curves from 5.7 to 17.3 dB/oct (normal range, 9.8–15.7 dB/oct). The nonasthmatic wheezing patients had normal exponential patterns in most of their analyzed sound segments. All patients had sharp peaks of power in many of the spectra of their expiratory and inspiratory lung sounds. The frequency range of the spectral peaks was 80–1,600 Hz, with some presenting constant frequency peaks throughout numerous inspiratory or expiratory sound segments recorded from one or more pickup locations. We compared the spectral shape, mode of appearance, and frequency range of wheezes with specific predictions of five theories of wheeze production: 1) turbulence-induced wall resonator, 2) turbulence-induced Helmholtz resonator, 3) acoustically stimulated vortex sound (whistle), 4) vortex-induced wall resonator, and 5) fluid dynamic flutter. We conclude that the predictions by 4 and 5 match the experimental observations better than the previously suggested mechanisms. Alterations in the exponential pattern are discussed in view of the mechanisms proposed as underlying the generation and transmission of normal lung sounds. The observed changes may reflect modified sound production in the airways or alterations in their attenuation when transmitted to the chest wall through the hyperinflated lung.
Gas mixing during high-frequency ventilation: an improved model
Authors: Khoo M. C. , Slutsky A. S. , Drazen J. M. , Solway J. , Gavriely N. , Kamm R. D.
Published: December 2017

A model for gas transport during high-frequency ventilation incorporating recently derived empirical forms for the effective diffusivity in oscillatory gas flow through a symmetrical branching network is proposed. The model accounts for the movement of gas among airways with changing cross-sectional area by using a moving-reference-frame analysis. The analysis technique incorporates the convective purging of the bias flow at the airway opening. The model predicts that although the cycle-averaged CO2 elimination rate (VCO2) depends most strongly on the product of frequency and tidal volume (VT), VT has an effect on its own, a finding consistent with published observations. This “VT effect” is due primarily to the oscillatory movement of gas from more central regions into peripheral regions where large cross-sectional areas promote efficient CO2 transport by molecular diffusion. Although the VT effect exists independent of the presence of a bias flow, placing the bias flow near the main carina can enhance the VT effect substantially. As VT is increased to values in the range of ordinary tidal breaths, VCO2 predicted by the model achieves close agreement with VCO2 deduced from conventional gas exchange theory.
Metabolic and respiratory hydrogen ion effects on hypoxic pulmonary vasoconstriction
Authors: Marshall C. , Lindgren L. , Marshall B. E.
Published: December 2017

Hypoxic pulmonary vasoconstriction (HPV) was studied in the ventilated-perfused rat lung in vitro. Respiratory acidosis and alkalosis were obtained by ventilating with 2, 7, or 10% CO2 (21% O2-balance N2). Metabolic acidosis and alkalosis were produced by the addition of 0.9 N NaHCO3 or 1 N lactic acid to the perfusate at constant PCO2. At each pH the pressor responses to 2 and 4% O2 were compared with the maximum pressor response (R%max) obtained with zero O2 and 5% CO2 at a normal pH (approximately 7.35). HPV was maximal when the [H+] was between 38 and 50 nM and was attenuated by changes of pH in either direction. Both respiratory and metabolic pH changes had similar effects. The combined linear regression equations were as follows: with 2% O2 the response to acidosis was R%max = 101.37 – 0.52 [H+] and to alkalosis was R%max = 2.03 [H+] - 3.85; with 4% O2 the response to acidosis was R%max = 56.88 – 0.3 [H+] and to alkalosis was R%max = 1.16 [H+] - 4.95. These effects were not due to changes of ionized calcium.
Change in extra-alveolar perimicrovascular pressure with lung inflation
Authors: Jasper A. C. , Goldberg H. S.
Published: December 2017

In eight isolated dog lobes, we examined the change in extra-alveolar perimicrovascular hydrostatic pressure (Pis) due to lung inflation. The vasculature was filled with autologous plasma. Pulmonary arterial and venous lines were connected to a common plasma reservoir. Perimicrovascular volume change (delta Vis), compliance (Cis), and the microvascular filtration coefficient (Kf) were derived from the change in lobe mass over time following a step increase in vascular pressure (Piv). Initially, transpulmonary pressure (PL) was 5 cmH2O and Piv = 0 cmH2O. At constant Piv, two sequential 5-cmH2O increases in PL increased Vis; division of delta Vis by Cis yielded the change in Pis attributable to lung inflation. Cis was 0.035 +/- 0.018 g X cmH2O–1 X g dry mass-1 (mean +/- SD) at PL = 15 cmH2O. Kf was 0.019 +/- 0.023 g X min-1 X cmH2O–1 X g dry mass-1. With inflation from PL = 5 to PL = 10 cmH2O, Pis = -2.15 +/- 1.76 cmH2O; from PL = 10 to PL = 15 cmH2O, Pis = -2.25 +/- 1.50 cmH2O. This perimicrovascular pressure change is very close to the perihilar interstitial pressure change reported by others. Such near equality suggests that the stress of lung inflation is very uniformly applied to the interstitial continuum.