bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of 100% oxygen on lung vascular function in awake sheep
Authors: Newman J. H. , Loyd J. E. , English D. K. , Ogletree M. L. , Fulkerson W. J. , Brigham K. L.
Published: December 2017

The purpose of this study was to define the time course of pulmonary toxicity during continuous breathing of 100% oxygen in adult sheep. Sheep were prepared for chronic measurement of vascular pressures, cardiac output, gas exchange, and for collection of lung lymph. Tracheostomies allowed accurate delivery of either 100% oxygen, compressed air, or hypoxic gas. Six sheep breathed 100% oxygen for 72–96 h, and four sheep breathed compressed air for 96 h. In addition to hypoxic challenges [fractional concentration of inspired O2 (FIo2) = 0.12], some sheep received prostaglandin H2 (PGH2)-analogue infusions to further assess pulmonary vascular reactivity. Lung lymph and blood chemotactic activity were measured by granulocyte migration in modified Boyden chambers. Postmortem lung water content and light microscopy were used to measure pulmonary edema. All sheep breathing 100% oxygen died between 72 (n = 2) and 96 h (n = 4). Sheep breathing oxygen demonstrated lung toxicity by measurements of 1) a fourfold increase in flow of protein-rich lung lymph, 2) increased alveolar-arterial difference in Po2 (greater than 20 Torr on FIo2 = 0.21) and hypercapnic acidemia, and 3) a mean extravascular lung water/dry lung weight of 5.7 (controls = 3.3), and histological evidence of interstitial and alveolar edema. Chemotactic activity in lung lymph at base line increased eightfold within 72–96 h of oxygen breathing. In sheep breathing oxygen, the hypoxic pressor response decreased by 50% at 48 h, and by 72–96 h there was a total absence of hypoxic vasoconstriction. There was no increase in lung lymph prostacyclin metabolite, and sodium meclofenamate did not restore the pressor response. In sheep breathing compressed air none of these changes in pulmonary vascular reactivity, lymph flow, or chemotactic activity occurred. We conclude that prolonged breathing of pure oxygen causes pulmonary edema by increasing lung vascular permeability and that respiratory failure results from both edema and loss of pulmonary vascular reactivity.
Noninvasive quantitative imaging of shape and volume of lungs
Authors: Hoffman E. A. , Sinak L. J. , Robb R. A. , Ritman E. L.
Published: December 2017

The Dynamic Spatial Reconstructor (DSR) can be used to determine detailed structure-to-function relationships or organ systems in vivo. A basic index of lung structure (shape and dimensions) is total lung volume. We checked the accuracy with which in vivo lung volumes can be measured by comparing lung volume (air plus tissue) determined by DSR scanning with that determined by excision and water displacement. Six dogs (2.5–26 kg) under morphine-pentobarbital anesthesia were scanned supine or prone at functional residual capacity and/or total lung capacity. With the trachea clamped at the lung volume scanned, a lethal dose of pentobarbital was administered, the lung excised, and its volume determined by water displacement. In vivo scan data were used to reconstruct adjacent 0.9-mm-thick transverse sections over the entire axial extent of the thorax. A three-dimensional surface-detection algorithm was used to generate shaded surface displays of the in situ lungs. The number of voxels (volume picture elements) of known dimensions contained within the three-dimensional image of the lung was summed to estimate total lung volume. Lung volumes calculated from the in vivo images ranged from -3.4 to +2.3% of the lung volume determined in vitro. The mean difference was 1.38 +/- 0.07% (SE). Regression analysis yielded an r value (correlation) of 1.00, a slope of 0.99, and an intercept of -4.35 ml. Multiple lung inflation steps scanned and analyzed in one dog showed similar accuracy. This technique is applicable to subjects with thorax dimensions up to 42 cm in cephalocaudal height and 39 cm in ventrodorsal and transverse diameters.
Quantitative measurement of intrapulmonary and extrapulmonary right-to-left shunt
Authors: Jones H. A. , Stradling J. R. , Clark J. C. , Davies E. E. , Rozkovec A.
Published: December 2017

We have developed a new technique that enables the shunting of blood from the right to the left side of the circulation to be partitioned into a cardiac and a lung component. The effects of recirculation are minimal, and the method does not require on-line data analysis. Quantitative estimates of these components have been made in two normal dogs and in five patients with raised pulmonary arterial pressures, some of whom were known to have a patent foramen ovale. The results were compared with oxygen shunt measured during air breathing. A poorly soluble gas, nitrogen, radiolabelled with 13N in solution is injected first into a central vein while matched samples of blood are drawn from the pulmonary artery and the aorta. A second solution containing 13N is injected into the right ventricle and sampled from the aorta only. Standardized gamma-counting techniques were used to analyze both the injected radioactivity and the radioactivity in the samples. These two measurements enable us to calculate the total right-to-left shunt, the pulmonary shunt, and by subtraction the extrapulmonary cardiac shunt.
Effect of endotoxin on airway responsiveness to aerosol histamine in sheep
Authors: Hutchison A. A. , Hinson J. M. , Brigham K. L. , Snapper J. R.
Published: December 2017

This study tested the hypothesis that in the awake sheep, airway responsiveness to aerosol histamine would be increased acutely by endotoxemia. Eleven sheep were chronically instrumented to allow for measurements of lung lymph flow, vascular pressures, and lung mechanics. Awake sheep were studied in a whole-body plethysmograph designed to measure dynamic compliance (Cdyn), resistance of the lung (RL), and functional residual capacity (FRC). Pulmonary responsiveness to aerosol histamine was assessed by giving five breaths of increasing concentrations of histamine (0.1–50 mg/ml) until Cdyn decreased to 65% (of control) or until 50 mg/ml of histamine had been given. Escherichia coli endotoxin (0.2–0.5 microgram/kg) was then infused, and at 5 h after endotoxemia pulmonary responsiveness to aerosol histamine was remeasured. After endotoxin, 9 of the 11 sheep exhibited decreased Cdyn at a lower concentration of histamine compared with the preendotoxin level (P less than 0.05). The mean of the log dose of histamine necessary to reduce Cdyn to 65% of control was 1.00 +/- 0.16 (SE) before endotoxin and 0.027 +/- 0.29 5 h after endotoxin; i.e., histamine responsiveness was increased. In the last 3 sheep studied, atropine (0.1 mg/kg iv) was given after the second aerosol histamine challenge, and a third dose-response curve was performed. Atropine did not return the endotoxin-induced increase in histamine responsiveness to base line. There was no correlation between the change in histamine responsiveness and the endotoxin-induced changes in Cdyn, FRC, RL, alveolar-arterial O2 difference, pulmonary arterial pressure, or lung lymph flow.
O2 transport during two forms of stagnant hypoxia following acid and base infusions
Authors: Cain S. M. , Adams R. P.
Published: December 2017

Cardiac output and mean arterial pressure were decreased in two groups of 16 anesthetized paralyzed dogs ventilated by pump. Pericardial tamponade was used in one group, and hemorrhagic hypotension was used in the other. After a 30-min control period and 30 min of circulatory shock by either method, 0.3N HCl was infused into half the dogs in each group and 1.0N NaHCO3 into the other half so that pH was separated by 0.3–0.4 units. The slope of the line relating O2 uptake to total O2 transport (blood flow X arterial O2 concentration) was used to evaluate how well the tissues extracted O2 relative to O2 supply. During the initial shock period before infusion, the slope of the line relating O2 uptake of left hindlimb skeletal muscle to total O2 transport in the limb was almost twice as great as that for the whole body. Acid infusion increased the slope of the whole-body line but did not alter that for the hindlimb. Base infusion, on the other hand, decreased the slope of the line for the limb during hemorrhagic shock but had no other effect. We concluded that acid either improved the distribution of a limiting blood supply to nonmuscle organ systems, or increased tissue capillary PO2 and O2 diffusion by decreasing hemoglobin O2 affinity (HOA), or both. The effect of an increased HOA with base infusion was noticeable in hindlimb skeletal muscle only when volume depletion by hemorrhage presumably greatly increased the normally short intercapillary diffusion distance in muscle.
Ventilatory and occlusion pressure responses to helium breathing
Authors: DeWeese E. L. , Sullivan T. Y. , Yu P. L.
Published: December 2017

To characterize the ventilatory response to resistive unloading, we studied the effect of breathing 79.1% helium-20.9% oxygen (He-O2) on ventilation and on mouth pressure measured during the first 100 ms of an occluded inspiration (P100) in normal subjects at rest. The breathing circuit was designed so that external resistive loads during both He-O2 and air breathing were similar. Lung resistance, measured in three subjects with an esophageal balloon technique, was reduced by 23 +/- 8% when breathing He-O2. Minute ventilation, tidal volume, respiratory frequency, end-tidal partial pressure of CO2, inspiratory and expiratory durations, and mean inspiratory flow were not significantly different when air was replaced by He-O2. P100, however, was significantly less during He-O2 breathing. We conclude that internal resistive unloading by He-O2 breathing reduces the neuromuscular output required to maintain constant ventilation. Unlike studies involving inhaled bronchodilators, this technique affords a method by which unloading can be examined independent of changes in airway tone.
Prostaglandin D2 inhibits hypoxic pulmonary vasoconstriction in neonatal lambs
Authors: Philips J. B. , Lyrene R. K. , McDevitt M. , Perlis W. , Satterwhite C. , Cassady G.
Published: December 2017

Intrapulmonary injections of prostaglandin D2 (PGD2) reduce pulmonary arterial pressure and resistance in fetal and hypoxic neonatal lambs without affecting systemic arterial pressure. This apparently specific pulmonary effect of PGD2 could be explained by inactivation of the agent during passage through the pulmonary capillary bed. We therefore studied the effects of both pulmonary and systemic infusions of PGD2 on the acute vascular response to a 1-min episode of hypoxia in newborn lambs. Since PGD2 has been reported to be a pulmonary vasoconstrictor in normoxic lambs, we also evaluated its effects during normoxemia. Pulmonary vascular pressures were not affected by either 1- or 10-micrograms . kg-1 . min-1 infusions into the left atrium or inferior vena cava during normoxia. Infusion of 1 microgram . kg-1 . min-1 PGD2 into the inferior vena cava decreased pulmonary vascular resistance and increased systemic arterial pressure. These two parameters were unchanged with the other three infusion regimens. Mean pulmonary vascular resistance rose 83% with hypoxia and no PGD2. PGD2 prevented any change in pulmonary vascular resistance with hypoxia, while systemic arterial pressure increased (1-microgram . kg-1 . min-1 doses) or was unchanged. Thus PGD2 specifically prevents hypoxic pulmonary vasoconstriction while maintaining systemic pressures, regardless of infusion site. PGD2 may be indicated in treatment of persistent pulmonary hypertension of the newborn and other pulmonary hypertensive disorders.
Effect of sleep state and hypercapnia on alae nasi and diaphragm EMGs in preterm infants
Authors: Carlo W. A. , Martin R. J. , Abboud E. F. , Bruce E. N. , Strohl K. P.
Published: December 2017

A coordinated activation of upper airway and chest wall muscles may be crucial in maintaining airway patency and ventilation. The alae nasi (AN) and diaphragm (DIA) electromyograms (EMG) were recorded with surface electrodes in 17 unsedated healthy preterm infants during both active (AS) and quiet sleep (QS). Airflow was measured via a nasal mask pneumotachograph and integrated to obtain tidal volume. Studies were performed during inhalation of room air and mixtures of 2 and 4% CO2 in air. In room air, phasic AN EMG accompanied 45 +/- 7% of breaths during AS compared with 14 +/- 5% of breaths during QS (P less than 0.001); however, with inhalation of 4% CO2 the incidence of AN EMG increased to comparable levels in both sleep states. During room air breathing onset of AN EMG preceded that of the DIA EMG and inspiratory airflow by 41 +/- 8 ms (P less than 0.01) and 114 +/- 29 ms (P less than 0.05), respectively. Peak AN activity preceded peak DIA activity by 191 +/- 36 ms (P less than 0.01). Alteration in sleep state or increasing chemical drive did not significantly alter these temporal relationships. Nevertheless, with each increase in end-tidal CO2, peak DIA EMG and tidal volume increased while peak AN EMG only showed a consistent increase during 4% CO2 inhalation. We conclude that although there exists a mechanism that temporally coordinates AN and DIA activation, the amount of AN EMG activity with each breath is not clearly correlated with DIA activation, which may contribute to the high incidence of respiratory dysrhythmias in preterm neonates.
Effect of tension and timing of contraction on the blood flow of the diaphragm
Authors: Bellemare F. , Wight D. , Lavigne C. M. , Grassino A.
Published: December 2017

An open-chest animal model was developed to study the diaphragmatic blood flow (Qdi) during bilateral electrophrenic stimulation. Two patterns of stimulation were used, continuous and intermittent, and both patterns were held at various transdiaphragmatic pressures (Pdi). The contractions were nearly isometric and held at an initial length of supine functional residual capacity (FRC). Qdi was measured in six dogs by catheterizing a branch of the diaphragmatic vein and by counting the blood drops with an infrared cell. During continuous contractions Qdi increased as a function of Pdi up to 70 +/- 12 ml . 100 g-1 . min-1 at 20% Pdimax. At higher levels Qdi decreased progressively and approached zero at 75% of Pdimax. A postcontraction hyperemia occurred at Pdi values greater than 20% Pdimax and increased as a function of Pdi. During intermittent contractions Qdi was a unique function of the diaphragmatic tension-time index (TTdi), a product of Pdi times the duty cycle (contraction time/total cycle time). Qdi increased progressively up to a TTdi of 25% Pdimax and decreased above that point toward zero at TTdi of 80% Pdimax. The postcontraction hyperemia appeared at a TTdi of about 15% of Pdimax and increased as a function of TTdi. It is concluded that Qdi is limited beyond a TTdi of about 20% Pdimax, as indicated by the increase in postcontraction hyperamia, and that Qdi is a function of both Pdi and the timing of contraction.
Effect of left pneumonectomy on lung mechanics in rabbits
Authors: Yee N. M. , Hyatt R. E.
Published: December 2017

Left pneumonectomy was performed in nine rabbits at 10 wk of age. Detailed pulmonary mechanics studies were performed at 14 wk of age in these rabbits and in nine littermate controls. Lung weight, total lung capacity, and static lung pressure-volume curves of the pneumonectomized rabbits were not different from those of the controls, but the forced vital capacity was smaller (P less than 0.05). Tantalum bronchograms of excised right lungs revealed no difference between controls and pneumonectomized rabbits in terms of bronchial diameter or pressure-area behavior of central or peripheral airways. Airways of pneumonectomized rabbits lengthened in accordance with the increase in lung volume. Over the midvolume range, the flow-limiting site moved from the trachea in controls to the right main bronchus in pneumonectomized rabbits. Maximal expiratory flow on air and on 80% He-20% O2 in the pneumonectomized rabbits average 70% of that in controls. This difference in flow was consistent with predictions based on the wave-speed theory of flow limitation.
Inhibition of hypoxia-induced ADH release by meclofenamate in the conscious dog
Authors: Walker B. R.
Published: December 2017

Release of antidiuretic hormone (ADH) due to hypoxic stimuli has been documented in several in vivo models. The current study was performed to determine whether 1) hypoxia causes ADH release in the conscious normovolemic dog and 2) whether endogenous prostaglandins are involved in hypoxic ADH release. Five conscious dogs were made hypoxic by inhalation of 10% O2. Dogs were studied both with and without pretreatment with meclofenamate (2 mg/kg iv and 2 mg . kg-1 . h-1). Hypoxic exposure resulted in elevated plasma ADH; however, meclofenamate totally blocked this response. Hemodynamic responses to hypoxia were unaffected by meclofenamate. In addition, plasma osmolality was unchanged by hypoxia in both groups. Since meclofenamate does not cross the blood-brain barrier, it is concluded that the release of ADH by hypoxia in the conscious dog may be mediated by endogenous prostaglandins produced outside the central nervous system. It appears that elevated renal prostaglandin release, increased ADH, and hemodynamic alterations could all interact to determine the final renal response to hypoxia.
Myoelectric signal versus force relationship in different human muscles
Authors: Lawrence J. H. , De Luca C. J.
Published: December 2017

An analytic study was initiated to investigate whether the normalized surface myoelectric signal vs. normalized force relationship varies in different human muscles and whether it is dependent on training level and rate of force production. The data were obtained from experiments that involved the biceps, deltoid, and first dorsal interosseous of three pianists, four long-distance swimmers, three power lifters, and six normal subjects. The elite performers (among the world's best) were chosen because they exhibited varying degrees of fine motor control, endurance training, and power training in different muscles. Approximately 200 isometric linearly force-varying contractions peaking at 80% of the maximal voluntary contraction level were processed. The results indicated that the myoelectric signal-force relationship was primarily determined by the muscle under investigation and was generally independent of the subject group and the force rate. Whereas this relationship was quasilinear for the first dorsal interosseous, it was nonlinear for the biceps and deltoid. Several possible physiological causes of the observed behavior of the myoelectric signal-force relationship are discussed.
Surface pH responses of muscles of different fiber-type composition to catecholamines
Authors: Kost G. J.
Published: December 2017

Catecholamines were infused intravenously for 45 min into pentobarbital sodium-anesthetized rabbits. Physiologically low-dose epinephrine (0.125 microgram . min-1 . kg-1) decreased medial gastrocnemius (MG) surface pH (SpH) 0.16 +/- 0.03 (SD) (P less than 0.001) to a low of 7.25 +/- 0.11 and soleus (S) SpH 0.09 +/- 0.04 (P less than 0.01) to a low of 7.33 +/- 0.08 without changing blood pressure significantly. Surface temperature measurements suggested a statistically insignificant small increase in local blood flow in both muscles. With 1.25 microgram . min-1 . kg-1 epinephrine, MG SpH decreased 0.22 +/- 0.05 (P less than 0.001) to a low of 7.17 +/- 0.06 and S SpH decreased 0.10 +/- 0.05 (P less than 0.02) to a low of 7.26 +/- 0.04. The MG SpH decrease exceeded the S SpH decrease in each experiment for both epinephrine infusion levels, and the incremental difference was significantly greater (P less than 0.02) with the higher dose, demonstrating a dose-response effect more pronounced for glycolytic compared with oxidative fibers. Norepinephrine infusions of 1.25 and 2.5 micrograms . min-1 . kg-1 did not change SpH of either muscle significantly, despite increases in blood pressure of 10 +/- 3 (P less than 0.002) and 19 +/- 10 mmHg (P less than 0.02), respectively.
Hemodynamic responses during prolonged sitting
Authors: Shvartz E. , Gaume J. G. , White R. T. , Reibold R. C.
Published: December 2017

Eight young men (group A) underwent 5 h of quiet sitting, preceded by 30 min of recumbency, 20 min of standing, and 20 s of walking, and five other young men (group B) underwent 70 min of sitting, preceded by recumbency only, to determine the effects of prolonged sitting and previous posture on hemodynamic responses (measured by impedance plethysmography). Group A showed more calf blood pooling and a decrease in thigh blood flow during sitting in comparison with the control group, but after 1 h of sitting hemodynamic responses of the two groups were similar. Sitting for 5 h (1st vs. 5th h) resulted in an increase in calf venous pooling (17%) and a decrease in calf BF (13%), a reduction in gravitational pooling in the thigh (corresponding to increased pooling in the calf), increases in diastolic and mean arterial pressures (6 and 7.3 mmHg, respectively), and minor changes in heart rate, stroke volume, and cardiac output. The results show that it is necessary to sit for 1 h before hemodynamic responses can be assessed in this position, regardless of the posture maintained previously. The main effect of prolonged sitting is pooling in the calf, which is compensated for by an increase in peripheral resistance.
Energetics of wet-suit diving in Korean women breath-hold divers
Authors: Kang D. H. , Park Y. S. , Park Y. D. , Lee I. S. , Yeon D. S. , Lee S. H. , Hong S. Y. , Rennie D. W. , Hong S. K.
Published: December 2017

Contemporary Korean women divers wear wet suits during diving work to avoid the cold water stress. The present study was undertaken to evaluate the effect of wearing wet suits on the daily thermal balance of divers and on the duration of diving work. Rectal (TR) and skin temperatures and O2 consumption (VO2) were measured in four divers before and during diving work in summer (22.5 degrees C water) and winter (10 degrees C water). Subjects wore either wet suits (protected) or cotton suits (unprotected) for comparison. TR decreased 0.4 degrees C in summer and 0.6 degrees C in winter after 2 h of diving work in protected divers, while it decreased to 35 degrees C in 60 min in summer and in 30 min in winter in unprotected divers. Mean skin temperature of protected divers decreased to 31 degrees C in summer and 28 degrees C in winter, while that of unprotected divers decreased to 24 degrees C in summer and 13 degrees C in winter. VO2 toward the end of the diving work period increased by 80 (summer) and 140% (winter) in protected divers and by 160 (summer) and 250% (winter) in unprotected divers. From these values total thermal cost of diving work was estimated to be 260 and 370 kcal . day-1 in summer and winter, respectively.
Gender differences in hypoxic vascular response of isolated sheep lungs
Authors: Wetzel R. C. , Sylvester J. T.
Published: December 2017

We compared the steady state stimulus-response relationship of the pulmonary circulation to graded hypoxia in isolated, in situ, blood-perfused lungs of postpubertal male and female sheep and male sheep of similar age that had been castrated within 1 wk of birth. The flow-resistive properties of the pulmonary circuit were assessed by pressure-flow curves generated over a wide range of flows (0-150 ml X min-1 X kg-1 body wt-1) at six different levels of inspired oxygen tension (PIo2) between 200 and 0 Torr. The stimulus-response relationship was quantitated by determining the pulmonary arterial pressures at a flow of 50 ml X min-1 X kg-1 (Ppa50) directly from these curves. We found that this relationship was biphasic, as previously described for other species, with a peak vasoconstrictor response at a PIo2 = 30 Torr. The isolated lungs of males and castrated males achieved a greater maximal pressor response (Ppa50 = 33 +/- 3.7 and 34.5 +/- 8 Torr, respectively) than did those of females (Ppa50 = 20.2 +/- 5.6 Torr, P less than 0.01). When the pulmonary vascular bed was maximally dilated (PIo2 = 0 Torr), there were no significant differences in the Ppa50 among the groups (Ppa50 = 15.8 +/- 4.6 in males, 11 +/- 3.5 in females, and 11.5 +/- 1.9 Torr in castrated males). There were no differences between males and castrated males at any PIo2. We conclude that the hypoxic pulmonary vasomotor response was attenuated in isolated lungs of postpubertal female sheep possibly due to the effect of female hormones.
Oxygen deficit and stores at onset of muscular exercise in humans
Authors: Di Prampero P. E. , Boutellier U. , Pietsch P.
Published: December 2017

Single-breath O2 consumption (VO2) at the mouth and heart rate were determined in five healthy male subjects at rest, during 8 min of cycloergometric exercise (50, 100, 125, and 150 W), and in the recovery period following two experimental conditions: air breathing throughout (AA); hypoxic breathing (FIO2 = 0.11) for 6 min of preexercise rest followed by air breathing from the onset of exercise (HA). The O2 deficits and debts as well as the t 1/2 values of the VO2 on- and off-responses were determined and blood lactate concentrations measured at rest and in the recovery after 4 and 8 min of exercise. At all work loads: 1) O2 deficits were on the average 0.39 liter smaller in HA than in AA; 2) VO2 on-responses were faster in HA (t 1/2 approximately equal to 7 s) than in AA (t 1/2 = 20-30 s); and 3) O2 debts and VO2 off-responses were the same in the two conditions. Since the VO2 and heart rate levels at steady state as well as the blood lactate concentrations after 4 and 8 min of exercise were the same in AA and HA, the observed differences of O2 deficit cannot be attributed to changes of energy metabolism in the two conditions; they therefore depend on the reduction of body O2 stores at rest in HA. This, independently measured, was found to be 0.46 liters, not far from the observed O2 deficit difference (0.39 liters). Thus a decrease of O2 stores before exercise is accompanied by a reduction of the O2 deficit and faster VO2 kinetics at the onset of exercise.
Acclimatization to high altitude in goats with ablated carotid bodies
Authors: Steinbrook R. A. , Donovan J. C. , Gabel R. A. , Leith D. E. , Fencl V.
Published: December 2017

In awake goats with ablated carotid bodies, we studied resting pulmonary ventilation, CO2 production, composition of arterial blood and cerebrospinal fluid (CSF), and ventilatory responsiveness to hyperoxic CO2 rebreathing at sea level (SL) and after 3 days at simulated high altitude (HA) (PB 446 +/- 5 Torr, equivalent to 4,300 m). At HA, resting pulmonary ventilation was increased, resulting in marked hypocapnia with appropriate base deficit in blood plasma; CSF became more alkaline; CO2-response curves were shifted to lower PCO2 levels, and their slopes were steeper than at SL. Although these changes in regulation of respiration were not demonstrably different from those seen after normal acclimatization to HA with carotid bodies intact, the mechanisms of their initiation and development are probably different.
Technique for making hollow central airway casts
Authors: Pedersen C. J. , Watson J. W. , Jackson A. C.
Published: December 2017

We have developed a method for producing rigid hollow casts of the central airways. Woods metal (melting point 70 degrees C) was poured into the airways at the trachea of an excised canine lung air-dried at a transpulmonary pressure of 30 cmH2O. The tissue was dissolved and removed, and the resulting negative cast was carefully trimmed leaving only airways with a diameter of 2 mm or greater. The cast was then electroplated with copper that provided a rigid jacket encasing the Woods metal. Heating this structure to 100 degrees C liquefied the Woods metal allowing the majority of it to flow out. Residual amounts were readily removed by a high-pressure steam hose attached to the trachea. Comparisons were made between airway diameters from in vivo radiographic bronchograms (DB) and direct measurements of the resulting trimmed Woods metal cast (DC). Linear regression analysis of these data indicated a high degree of correlation (DC = 0.98 DB + 0.03, r = 0.99). We concluded that this technique produces positive casts which provide a good representative model of the central airways.
A respiratory function jacket for measuring tidal volume and changes in FRC
Authors: Cartwright D. W. , Gregory G. A. , Willis M. M.
Published: December 2017

We describe a simple application of a mercury-in-rubber strain gauge in a jacket used to measure tidal volume in paralyzed, mechanically ventilated rabbits. The jacket produces a record with a straight base line. Shifts of this base line can be used to assess changes in functional residual capacity (FRC).
Graphical analysis of multiple inert gas elimination data
Authors: Stewart W. E. , Mastenbrook S. M.
Published: December 2017

A plot of measured retention-excretion ratios [(Ri/Ei)obs] vs. reciprocal solubility (1/lambda i) for selected inert gases allows quick detection of shunt and ventilation-perfusion (V/Q) inhomogeneity in the lung. We derive simple rules for constructing a smooth R/E function from the data, using a multicompartmental model of the lung. If mixed venous inert gas measurements are available, the values [lambda i(1-Ri)/Ei]obs for the infused gases can be used to estimate the overall VT/QT ratio and provide an additional test of the consistency of the data. For any set of equilibrium compartments ventilated and perfused in parallel, we show that d(R/E)/d(1/lambda) cannot be negative, nor can d2(R/E)/d(1/lambda)2 be greater than zero. A rectilinear R/E function implies a narrow distribution of V/Q among the gas exchange compartments, whereas a downward-concave curve implies a broader distribution. The shunt perfusion and dead-space ventilation can be estimated from the asymptotes of the R/E function. The range of V/Q for the gas exchange compartments can also be bracketed if a well-defined region of curvature is present in the graph. Finally, from the R/E vs. 1/lambda graph and (if mixed venous data are available) from the lambda(1-R)/E values, we can determine quickly whether the data deserve the detailed numerical analysis outlined in our companion paper.
Parametric estimation of ventilation-perfusion ratio distributions
Authors: Stewart W. E. , Mastenbrook S. M.
Published: December 2017

We present a model and rigorous statistical approach for recovery of ventilation-perfusion ratio (V/Q) distribution parameters from multiple inert gas elimination data. We model the lung as a parallel combination of shunt, dead space, and one to three log-normal distributions of gas exchange units. This model provides a natural set of parameters for characterizing V/Q distributions. The log-normal terms are adjustable to represent smooth or sharp peaks in the distribution. Since the peak locations and widths are explicit in the model, very few parameters are needed. We select and estimate the significant parameters of the model by use of standard statistical tests and constrained least squares. This method provides two major advances in V/Q distribution estimation: 1) it allows flexible pooling and statistical comparisons of multiple experiments, and 2) it simultaneously gives both point estimates and 95% probability intervals for the V/Q distribution parameters. We present results of our procedure for data from humans in health, stress, and pulmonary disease. A program package, VQPAR, in FORTRAN is available for implementing the procedure.
Force reserve of the diaphragm in patients with chronic obstructive pulmonary disease
Authors: Bellemare F. , Grassino A.
Published: December 2017

The fatigue threshold of the human diaphragm in normal subjects corresponds to a transdiaphragmatic pressure (Pdi)-inspiratory time integral (TTdi) of about 15% of Pdimax. The TTdi of resting ventilation was measured in 20 patients with chronic obstructive pulmonary disease (COPD) and ranged between 1 and 12% of Pdimax (mean 5%). TTdi was significantly related to total airway resistance (Raw) (r = 0.57; P less than 0.05). Five of these patients were asked to voluntarily modify their TI/TT (ratio of inspiratory time to total cycle duration; from 0.33 to 0.49) so as to increase their TTdi from a control value of 8% to an imposed value of 17% of Pdimax. The imposed pattern induced a progressive decline in the high-frequency (150-350 Hz)/low-frequency (20-40 Hz) power ratio (H/L) of the diaphragm electromyogram (fatigue pattern), quantitatively similar to that seen in normal subjects breathing with similar TTdi levels. The decay in H/L was followed by a progressive fall in mean Pdi meanly due to decrease in gastric pressure swings. It is concluded that 1) the force reserve of the diaphragm in COPD patients is decreased because of a decrease in Pdimax; 2) the remaining force reserve of the diaphragm can be exhausted by even minor modifications in the breathing pattern; and 3) at a TI/TT of 0.40 our COPD patients can increase their mean Pdi 3-fold before reaching a fatiguing pattern of breathing compared with 8-fold in normal subjects.
Vagal feedback with expiratory threshold load under extracorporeal circulation
Authors: Jammes Y. , Bye P. T. , Pardy R. L. , Roussos C.
Published: December 2017

In 11 anesthetized dogs placed under extracorporeal circulation, the vagal feedback was tested by electrical stimulation of the vagus nerves with cold block of their caudal part and by passive lung hyperinflation. The apneic response to such vagal stimulation progressively disappeared during expiratory threshold load breathing but then returned to control values some minutes after the load was removed. This suppression of the inhibitory response to stimulation of the vagus nerves was usually observed when vagal afferents were intact or blocked by cold. However, it was not observed whether no evoked activity continued in expiratory muscles after the cold block, or after suppression of all proprioceptive muscular afferents after transection of the spinal cord at C6 level. These results strongly suggest that enhancement of proprioceptive inputs to the respiratory centers counteracts the vagally mediated inspiratory “off-switch” mechanisms.
Lactate in human skeletal muscle after 10 and 30 s of supramaximal exercise
Authors: Jacobs I. , Tesch P. A. , Bar-Or O. , Karlsson J. , Dotan R.
Published: December 2017

The purpose of this study was to evaluate the extent of anaerobic glycogenolysis, as indicated by intramuscular lactate concentration, after 10 and 30 s of supramaximal exercise and to compare male and female subjects in this regard. Fifteen males and seven females performed two cycle exercise bouts against a resistance which was standardized so that one pedal revolution resulted in 4.90 J work X kg body wt-1. A muscle biopsy was obtained after 10- and 30-s exercise bouts and analyzed for lactate concentration. The lactate concentrations averaged 36 and 61 mmol X kg dry wt-1 after the 10- and 30-s exercise bouts, respectively. The male subjects had higher (P less than 0.005) lactate concentrations and generated higher (P less than 0.001) power outputs for both exercise bouts. When the mean lactate concentrations were statistically adjusted after controlling for between-group variation in power output, no difference was evident between groups for the 10- or the 30-s lactate value. The results are evidence that pronounced lactate accumulation occurs during supramaximal exercise of a 10-s duration, suggesting that glycolysis can occur within this time frame. This is in contrast to the theory that glycolysis does not occur until endogenous phosphagen levels reach some critically low value, not thought to be obtainable within the first 10 s of supramaximal exercise.
Stimulation of splanchnic afferents reflexly relaxes tracheal smooth muscle in dogs
Authors: Rybicki K. J. , Longhurst J. C. , Kaufman M. P.
Published: December 2017

Although chemical stimulation of abdominal visceral afferents has been shown to reflexly increase cardiovascular and ventilatory function, the effect of stimulating these afferents on airway smooth muscle is unknown. Therefore, we recorded transverse smooth muscle tension from an innervated segment of trachea in chloralose-anesthetized dogs while we topically applied capsaicin (200 micrograms/ml) and bradykinin (0.01-10 micrograms/ml) to the serosal surfaces of the stomach, small intestine, and gallbladder. Application of these irritant substances to the stomach and small intestine decreased tracheal tension and increased mean arterial pressure. However, application of capsaicin and bradykinin to the gallbladder had only small effects on both of these variables. Cutting the splanchnic nerves abolished or greatly attenuated the decreases in tension and increases in mean arterial pressure, whereas cutting the vagi had no effect on them. We conclude that stimulation of splanchnic afferent endings in the stomach and small intestine reflexly relaxes tracheal smooth muscle in dogs. This effect may be one component of the constellation of autonomic responses reflexly evoked by abdominal visceral pain and inflammation.
Maximal exercise responses of tetraplegics and paraplegics
Authors: Coutts K. D. , Rhodes E. C. , McKenzie D. C.
Published: December 2017

Eight tetraplegic and 13 paraplegic subjects performed a continuous progressive loading exercise test to exhaustion on a wheelchair ergometer. Their cardiorespiratory responses at maximal O2 uptake were analyzed after initially grouping subjects according to the international system for classification of wheelchair athletes. Analysis of variance provided a basis for regrouping the subjects into tetraplegic (T), high-lesion paraplegic (HLP), and low-lesion paraplegic (LLP) groups and indicated significant differences (P less than 0.05) in maximal power output (24, 47, and 80 W) and O2 uptake (0.97, 1.62, and 2.42 l/min) for T, HLP, and LLP, respectively. T had a significantly lower maximal heart rate (110) compared with the paraplegic values (175 and 190), whereas the HLP, in contrast to the LLP, had a lower maximum ventilation (66 vs. 101 l/min) and a lower O2 pulse (9.3 vs. 12.7 ml/beat). The ventilatory equivalent for O2 was similar in all groups to values for able-bodied subjects in maximal arm crank ergometry, however, suggesting a lack of any respiratory limit to maximal O2 delivery. No differences were noted in respiratory exchange ratio or net efficiency between the groups. In addition to limitations of functional muscle mass, the data suggested that the reduced cardiac capacity of T and HLP may also be linked to their lower maximal exercise capacity and O2 uptake.
Mechanical and gas-distribution behavior of a collateral ventilation model
Authors: Cutillo A. G. , Durney C. H. , Renzetti A. D.
Published: December 2017

We extended the theoretical analysis of Otis et al. (J. Appl. Physiol. 8: 427-443, 1956) to study the effects of collateral ventilation on lung mechanics and gas distribution. Equations were developed to express the effective compliance, the effective resistance, and the distribution of airflow and tidal volume in a two-compartment model incorporating a collateral communication. The analysis of the model showed that, in general, collateral ventilation tends to attenuate the degree of frequency dependence of compliance and resistance, the magnitude of this effect being dependent on the mechanical properties of the model, including collateral resistance. The influence of collateral ventilation is important when the model simulates the mechanical characteristics of the emphysematous lung (marked time-constant inequality with regionally high airway resistance, and relatively low collateral resistance). Under these conditions, a large fraction of the tidal volume of the high airway resistance lung compartment is contributed by the collateral communication. The effects of collateral ventilation on the mechanical behavior of the model are negligible when collateral resistance largely exceeds airway resistance (simulating experimental findings in normal lungs). The present theoretical data suggest that the use of equations based on a model incorporating collateral ventilation is justified, at least in predicting the mechanical and gas-distribution behavior of the lung in emphysema.
Regional left ventricular performance during normal and obstructed spontaneous respiration
Authors: Robotham J. L. , Badke F. R. , Kindred M. K. , Beaton M. K.
Published: December 2017

To clarify the effects of respiration on left ventricular (LV) dimensions and shortening, we studied chronically instrumented dogs with endocardial sonomicrometer crystals in the anterior-posterior (AP), septal to lateral (SL), and long axes (LA) following pericardiectomy. Ten anesthetized dogs were examined during spontaneous unobstructed respiration, partial inspiratory obstruction (PIO), and Mueller maneuvers (MM). During unobstructed inspiration, end-diastolic dimensions (EDD) demonstrated a significant increase in the AP and a similar decrease in the SL axis (i.e., noncongruent shape changes). During PIO only the SL EDD diminished significantly, while no significant changes occurred in any EDD during MM. Individual dogs also demonstrated noncongruent shape changes at end systole during inspiration. However, the end-systolic dimensions for the entire group demonstrated a significant increase in one dimension during each inspiratory mode with no significant changes in the other two axes suggesting an increased ventricular volume. Regional shortening declined only in the SL axis during both unobstructed respiration and PIO. Spontaneous sighs with large tidal volumes, yet smaller changes in pleural pressure than during the MM, were associated with marked noncongruent shape changes in both diastole and systole. We conclude that 1) estimates of LV volumes during respiration based on only one or two axes and assuming regional congruent shape changes may be misleading; and 2) lung volume changes can affect LV geometry independently of changes in pleural pressure.
Breath-by-breath alveolar gas exchange
Authors: Giezendanner D. , Cerretelli P. , Di Prampero P. E.
Published: December 2017

A method is described for breath-by-breath measurement of alveolar gas exchange corrected for changes of lung gas stores. In practice, the subject inspires from a spirometer, and each expired tidal volume is collected into a rubber bag placed inside a rigid box connected to the same spirometer. During the inspiration following any given expiration the bag is emptied by a vacuum pump. A computer monitors inspiratory and expiratory tidal volumes, drives four solenoid valves allowing appropriate operation of the system, and memorizes end-tidal gas fractions as well as mixed expired gas composition analyzed by mass spectrometer. Thus all variables for calculating alveolar gas exchange, based on the theory developed by Auchincloss et al. (J. Appl. Physiol. 21: 810-818, 1966), are obtained on a single-breath basis. Mean resting and steady-state exercise gas exchange data are equal to those obtained by conventional open-circuit measurements. Breathing rates up to 30 X min-1 can be followed. The breath-to-breath variability of O2 uptake at the alveolar level is less (25-35%) than that measured at the mouth as the difference between the inspired and expired volumes, both at rest and during exercise up to 0.7 of maximum O2 consumption.
Substrates for cold thermogenesis in thyrotoxic dogs
Authors: Minaire Y. , Forichon J. , Freminet A. , Cagnard M. , Dallevet G.
Published: December 2017

The influence of thyrotoxicosis on energy supply during cold exposure was studied in normal and chronically thyroxine (T4)-treated normothermic dogs exposed to neutral (Ta,N = +25 degrees C) or cold (Ta,C = -21 degrees C) ambient temperatures. At Ta,N, T4 treatment significantly increased VO2, glucose turnover, and plasma 3-hydroxybutyrate concentration. The percentage of glucose turnover derived from alanine also increased in spite of lower alanine release. In cold, T4 treatment did not significantly modify O2 consumption, glucose turnover, or plasma alanine concentration, but plasma hydroxybutyrate, alanine clearance, and alanine conversion into glucose were significantly increased compared with control. It is suggested that in cold the main effect of thyrotoxicosis on energy supply, in addition to a trend toward lipid mobilization, is an increase in hepatic alanine extraction and conversion into glucose in the presence of lower muscular alanine delivery.
Contribution of hypoventilation to sleep oxygen desaturation in chronic obstructive pulmonary disease
Authors: Hudgel D. W. , Martin R. J. , Capehart M. , Johnson B. , Hill P.
Published: December 2017

The purpose of this study was to determine whether hypoventilation contributes to the sleep hypoxemia observed in chronic obstructive pulmonary disease (COPD) patients and to examine breathing pattern and respiratory muscle electromyographic (EMG) activity during these episodes. Seven COPD patients who experienced at least a 10% decrease in arterial O2 saturation (SaO2) during rapid-eye-movement sleep (REM) sleep, six COPD patients with a minimal fall in SaO2, and five healthy subjects were studied. An inductance vest was used to quantitate ventilation. Skin electrodes were used to estimate diaphragmatic and intercostal electromyographic activity. Minute ventilation and EMG activity decreased in all three groups during sleep. Ventilation was irregular during REM sleep in the patients. During REM sleep, desaturating patients had longer episodes of hypopneic breathing [30 +/- 8 s (SE)] than nondesaturating patients (13 +/- 1 s, P less than 0.01). Desaturating patients spent a greater proportion of REM time hypopneic (53 +/- 5 vs. 28 +/- 5%, P less than 0.01) and had a greater decrease in functional residual capacity during hypopnea (P less than 0.05). SaO2 followed the hypopneic and hyperpneic breathing in REM sleep so that desaturating patients had more time for desaturation to occur. Thus hypoventilation appears to be a primary factor in sleep O2 desaturation in these patients. Because of the fall in lung volume, maldistribution of ventilation may also contribute.
Instantaneous cardiac acceleration in the cat elicited by peripheral nerve stimulation
Authors: Gelsema A. J. , De Groot G. , Bouman L. N.
Published: December 2017

The short-latency effect of peripheral nerve stimulation on heart rate was studied in decerebrate cats. Stimulus trains (100 Hz) of 1-s duration were given to the tibial nerve or to muscle nerves with an intensity yielding a maximal force of isometric contraction of the triceps surae muscle. The first detectable sign and the maximum of cardiac cycle length shortening were found at 0.5-0.6 and 2.1 +/- 0.4 (SD) s, respectively, after the onset of stimulation. A positive correlation exists between the basic cycle length (i.e., before nerve stimulation) and the stimulation-induced shortening of cycle length. The average maximum shortening was found to be 6.7% of basic cycle length. Atropine (0.05-0.1 mg/kg) or bilateral vagotomy suppresses the heart rate response almost completely, whereas the administration of propranolol (2 mg/kg) leaves the response intact. When the nerve is cut proximal to the site of stimulation, the response disappears. Paralysis of the muscle diminishes the response upon nerve stimulation. It is concluded that the short-latency response studied here can be considered as a muscle-heart reflex that is similar to the one previously found in humans.