bluuebunny/crossref_metadata_2025 huggingface dataset:
Distribution of ventilation and diffusing capacity in the normal and diseased lung
Authors: Lewis S. M. , Rubin D. Z. , Mittman C.
Published: December 2017

Conventional tests of diffusing capacity (DL) consider the lung to be a uniform structure with regard to both ventilation and diffusion. These assumptions are incorrect even in normal subjects. We present a method for determining the distribution of both specific ventilation (SV) and DL from the washin and washout of C18O and simultaneous washout of argon. Both end-tidal and mixed-expired data are fit to a two-compartment lung model; parameters that define SV and DL are assigned to each compartment. From data generated by a model, the parameters recovered were found to be relatively insensitive to realistic levels of noise. Measurements in one subject were highly repeatable. We examined 15 normal subjects and 16 subjects with varying degrees of obstructive lung disease. In both groups the better ventilated spaces generally showed a higher DL. The sum of the total two-compartmental DL's correlated with, but was found to exceed, the value obtained using the steady-state method and generally exceeded the single-breath result. We conclude that this method has potential advantages over conventional methods and is worthy of further study.
Activity of respiratory muscles in upright and recumbent humans
Authors: Druz W. S. , Sharp J. T.
Published: December 2017

It is established that during tidal breathing the rib cage expands more than the abdomen in the upright posture, whereas the reverse is usually true in the supine posture. To explore the reasons for this, we studied nine normal subjects in the supine, standing, and sitting postures, measuring thoracoabdominal movement with magnetometers and respiratory muscle activity via integrated electromyograms. In eight of the subjects, gastric and esophageal pressures and diaphragmatic electromyograms via esophageal electrodes were also measured. In the upright postures, there was generally more phasic and tonic activity in the scalene, sternocleidomastoid, and parasternal intercostal muscles. The diaphragm showed more phasic (but not more tonic) activity in the upright postures, and the abdominal oblique muscle showed more tonic (but not phasic) activity in the standing posture. Relative to the esophageal pressure change with inspiration, the inspiratory gastric pressure change was greater in the upright than in the supine posture. We conclude that the increased rib cage motion characteristic of the upright posture owes to a combination of increased activation of rib cage inspiratory muscles plus greater activation of the diaphragm that, together with a stiffened abdomen, acts to move the rib cage more effectively.
Effect of hypoxia and CO on a cytochrome P-450-mediated reaction in rabbit lungs
Authors: Knoblauch A. , Sybert A. , Brennan N. J. , Sylvester J. T. , Gurtner G. H.
Published: December 2017

Evidence indicates that the diffusion of O2 and CO in tissue may be facilitated by a carrier molecule having a P50 that approximates tissue O2 partial pressure (PO2; 1–15 Torr) and a much higher affinity for CO than for O2. To determine whether cytochrome P-450 in lung satisfies these criteria, we measured the effect of hypoxia and of CO on the rate of metabolism of the cytochrome P-450 mediated O-demethylation of p-nitroanisole in isolated perfused rabbit lungs. Metabolism was inhibited by 50% of a control at an estimated tissue PO2 fo 4 Torr (5.5 microM). When inspired CO2 was kept at 200 Torr and inspired CO partial pressure (PCO) varied an estimated tissue PCO/PO2 ratio of 0.025 reduced the reaction rate by 50% of control, but some metabolism persisted at PCO/PO2 ratios larger than one. The relationship between reaction rate and PCO/PO2 ratio could not be fit by a single value for Haldane constant for M (CO affinity/O2 affinity) but could be described with a two-component model in which metabolism was equally divided between a high-affinity cytochrome (M = 200) and a low-affinity cytochrome (M = 2). These findings suggest that cytochrome P-450 could act as a carrier for O2 and CO in tissue with low PO2's.
Effect of positive end-expiratory pressure and body position in unilateral lung injury
Authors: Hasan F. M. , Beller T. A. , Sobonya R. E. , Heller N. , Brown G. W.
Published: December 2017

Positive end-expiratory pressure (PEEP), by increasing lung volume in acute lung injury, may recruit terminal air spaces in the involved regions, but may also distend noninvolved regions increasing extravascular lung water and worsening gas exchange. We investigated the effect of increasing levels of PEEP on arterial oxygenation in 26 anesthesized dogs with unilateral acid pneumonitis and studied the influences of gravity and distribution of the injury on this effect. Arterial PO2 was consistently higher when the noninjured lung was dependent than in the supine or injured lung-dependent positions. Low levels of PEEP (5, 10 cmH2O) improved arterial oxygenation and reduced intrapulmonary physiological shunt. However, 15 cmH2O PEEP resulted in worsening of gas exchange, increased dead space ventilation, and diminished static compliance. The adverse effects of high levels of PEEP on arterial oxygenation were similar whether the injured lung was dependent or not and were evident a lower levels of PEEP in one group of dogs in which the unilateral injury was more diffuse and in which the upper and middle lobes were also involved. Thus, the compressive effects of high levels of PEEP on alveolar capillaries in the noninjured lung are influenced by the extent and distribution of injury in the injured lung, but not by local forces governing regional blood flow distribution.
Changes in breathing pattern mediated by intrapulmonary CO2 receptors in chickens
Authors: Tallman R. D. , Kunz A. L.
Published: December 2017

The ventilation of unanesthetized tracheostomized chickens was measured using a whole-body plethysmograph. The inspired CO2 fraction was quickly manipulated between 0.05 and 0.0 in such a way as to limit the fresh air inspired to a fixed duration pulse preceded and followed by 5% CO2. As was previously shown with this experimental protocol [Tallman et al., Am. J. Physiol. 237 (Regulatory Integrative Comp. Physiol. 6): R260–R265, 1979], the duration of inspiration and expiration (TI and TE, respectively) was dependent on the timing, relative to inspiration, that the pulse of air arrived at the lung. To study the possible involvement of arterial chemoreceptors in this reflex, a method of denervating the carotid chemoreceptors in this reflex, a method of denervating the carotid bodies was developed. After denervation, the hyperpneic response to intravenous NaCN and 2–3 breaths of N2 was eliminated, indicating the complete removal of arterial chemoreflexes. When tested with the same protocol of CO2 inhalation following carotid body denervation, TI and TE were still dependent on the delay of the fresh air pulse. These experiments support the conclusion that intrapulmonary CO2 receptors (IPC) mediate the reflexes studied and provide evidence that IPC affect the phase-switching mechanisms on a breath-to-breath basis.
Pulmonary gas exchange during altered density gas breathing
Authors: Christopherson S. K. , Hlastala M. P.
Published: December 2017

The alveolar-arterial O2 partial pressure difference (PAO2 - PaO2) has been shown to decrease as carrier-gas density increases. This study was designed to confirm or deny the hypothesis that the improvement in O2 exchange is a result of density-dependent changes in the alveolar ventilation-perfusion (VA/Q) distribution. On changing from heliox breathing to air breathing, there was an improvement in oxygen exchange along with a slight worsening of VA/Q distribution. The conclusion is reached that changes in VA/Q distribution due to altered carrier-gas density are not responsible for changes in O2 exchange. A possible explanation is related to the interaction of diffusion and convection on inspiration, which may cause inspired gas distribution to be different from overall ventilation distribution. The interesting implication is that gas exchange properties of gases eliminated from the blood and exhaled are not necessarily symmetrical to the properties of gases inhaled and taken up by the blood.
Activation of the parasternal intercostals during breathing efforts in human subjects
Authors: Troyer André De , Sampson Michael G.
Published: December 2017

Page 524: André De Troyer and Michael G. Sampson. “Activation of the parasternal intercostals during breathing efforts in human subjects.” Page 529: column 2, paragraph 2 should read: In conclusion the observations reported in this study are interpreted to indicate that the inspiratory EMG activity present in the parasternal intercostal muscles during quiet breathing depends on a central inuohntary mechanism and not on intercosttal mechanoreceptors.
Respiratory mechanics in supine subjects during progressive partial curarization
Authors: Gal T. J. , Arora N. S.
Published: December 2017

Respiratory mechanics were studied in six supine conscious volunteers during progressive muscle weakness produced by infusion of d-tubocurarine. Partial curarization was carried out to the point of abolishing head lift ability and handgrip strength. At all levels of partial paralysis, expiratory muscle strength was significantly more impaired than inspiratory strength. Despite this, subjects maintained relatively normal maximal expiratory flow rates, whereas inspiratory flows decreased significantly. The diminished inspiratory flows are not fully explained by decreased driving pressures during force inspiration, since inspiratory resistance increased significantly with the decreased flow. Inspiratory flow patterns suggest a variable extrathoracic obstruction most likely due to the absence of normal airway abductor activity during inspiration. Maximal respiratory muscle weakness decreased forced vital capacity by 29% and total lung capacity by 15%. The decreased level of lung inflation did not alter lung elastic recoil. Functional residual capacity was unchanged, but inspiratory capacity decreased by 25% and residual volume increased by 38%. These changes are in accord with predictions based on the decreased muscle strength and normal respiratory system recoil.
Impaired cardiac "acceleration" at the onset of exercise in patients with coronary disease
Authors: Zimmerman P. , Heigenhauser G. J. , McCartney N. , Sutton J. R. , Jones N. L.
Published: December 2017

The responses to two levels of exercise (400 and 800 kpm/min) were studied in nine untrained healthy subjects and seven patients with coronary artery disease. Measurements were made over 20-s time intervals to obtain the half times (t1/2) of the asymptotic rise in cardiac frequency (fc), O2 intake (VO2), CO2 output (VCO2), and ventilation (VE). Complete data were obtained in both groups at 400 kpm/min, but only in healthy subjects at 800 kpm/min, as patients were unable to exercise for longer than 2 min at this power. At the onset of 400 kpm/min, t1/2 for VO2 was similar, but t1/2 for fc, VCO2, and VE were all longer in the patients. At 800 kpm/min there was a delay in VO2 in the patients before stopping exercise. In patients and healthy subjects t1/2 for VCO2 and VE, but not VO2, were related to t1/2 for fc. The results emphasized the importance of tissue CO2 storage in attenuating the delivery of CO2 to the lungs and thus delayed the ventilatory response to a step increase in power output.
Isovolume pressure-flow relationships in intrapulmonary bronchi of excised dog lungs
Authors: Suzuki S. , Sasaki H. , Sekizawa K. , Takishima T.
Published: December 2017

From excised dog lungs we isolated airtight the intrapulmonary main bronchi (5–6 cm in length) with beads according to the technique described by Takishima et al. (J. Appl. Physiol. 38: 875–881, 1975), except for the most distal bronchus in which a retrograde catheter was inserted into the pleural surface of the lung. Air flowed from the retrograde catheter to the isolated main lobar bronchi at a given transpulmonary pressure (PL) with variable dynamic rates of driving pressure. We studied isovolume pressure-flow (IVPF) curves in the isolated intrapulmonary bronchi. The IVPF curves showed maximum expiratory flow (Vmax) and negative effort dependence. Vmax increased with increased PL and with increased dynamic rate of driving pressure and decreased with increased peripheral airway resistance added to the retrograde catheter. Bronchograms showed that dynamic compression occurred near the outlet of the isolated bronchi. When the isolated bronchi were dissected free from the surrounding parenchyma, Vmax decreased by 20–30% compared with Vmax in intact bronchi. We concluded that Vmax in intrapulmonary bronchi is preserved by mechanical interdependence between bronchi and parenchyma.
Correlations of maximum expiratory flow with small airway dimensions and pathology
Authors: Berend N. , Thurlbeck W. M.
Published: December 2017

Pressure-volume and maximum expiratory flow-volume curves with air and a He-O2 mixture were performed in 25 excised human lungs. Small airway dimensions were measured, and the degree of various small airway lesions and emphysema was graded. Correlations were then made between the maximum flow (Vmax) at a transpulmonary pressure (PL) of 5 cmH2O and these measurements and scores. Small airway dimensions correlated poorly with Vmax. However, significant correlations were obtained between Vmax and the inflammation score (P less than 0.05), fibrosis score (P less than 0.05), and emphysema grade (P less than 0.01) but not smooth muscle hyperplasia or pigmentation. Neither the increase in flow with He-O2 nor the volume of flow correlated significantly with any small airway measurement or score.
Pulmonary microvascular permeability following E. coli endotoxin and hemorrhage
Authors: Kinnebrew P. S. , Parker J. C. , Falgout H. J. , Taylor A. E.
Published: December 2017

The effects of hemorrhage and Escherichia coli endotoxin on vascular permeability in the lung were investigated in open-chest dogs. Systemic arterial, pulmonary artery, and left arterial pressures were monitored, and a 30-ml balloon catheter placed in the left atrium. An afferent to the left hilar lymph node was cannulated and lymph flow monitored. Lymph and plasma protein concentrations were measured by refractometry. The animals were divided into three groups: 1) a control group in which left atrial pressure was increased by inflation of the left atrial balloon; 2) a hemorrhagic shock group, bled to a systemic arterial pressure of 35–40 Torr until uptake of 20% of shed blood from the reservoir; and 3) an endotoxin shock group in which 2 or 4 mg/kg E. coli endotoxin was infused and left atrial pressure increased to 18 cmH2O for 2 hr. Permeability was determined by comparing the lymph/plasma protein ratios as a function of pulmonary lymph flow for the three groups at base line and increased left atrial pressures. There were no significant differences in lymph protein “wash down” between hemorrhage and control, and there was a minimal but significant difference between endotoxin and control groups. Postmortem extravascular lung water was not increased in the hemorrhage and endotoxin groups when compared to control. Therefore, there were no acute changes in lung vascular permeability within 2 hr after severe hemorrhage, but a minimal increase in permeability following endotoxin.
Isotopic analysis of leucine and urea metabolism in exercising humans
Authors: Wolfe R. R. , Goodenough R. D. , Wolfe M. H. , Royle G. T. , Nadel E. R.
Published: December 2017

We have used the primed constant infusion of di-[15N]urea and [1–13C]leucine to determine the effects of mild exercise (approx 30% Vo2max for 105 min) on urea production and leucine metabolism in human subjects. The oxidation of plasma leucine was distinguished from the oxidation of leucine that never entered the plasma pool (“intracellular” leucine) by means of determining the enrichment of alpha-ketoisocaproic acid (alpha-KICA). Total leucine oxidation increased from 0.38 +/0 0.05 to 1.41 +/- 0.14 micromol . kg-1 . min-1 during exercise due to increases in the oxidation of plasma leucine (150%) and intracellular leucine (600%). Plasma leucine flux decreased slightly, but not significantly (0.1 greater than P greater than 0.05), and the percent of alpha-KICA derived from plasma leucine dropped significantly (P less than 0.05) from 79.5 +/- 4.3 at rest to 62.0 +/- 5.3% over the last 30 min of exercise. Despite the increase in leucine oxidation during exercise, urea concentration and production did not change. Thus in exercise urea production does not accurately reflect all aspects of amino acid metabolism.
A simply constructed treadmill for rodent exercise studies
Authors: Rubin S. A. , Mickle D.
Published: December 2017

A treadmill suitable for studying the exercise physiology of small rodents was constructed. The treadmill itself is a belt sander mounted in an inverted position. Grade elevation is provided by securing the treadmill to a hinged platform. Speed variation is provided by a variable output power supply. Enclosure of the treadmill allows measurement of oxygen consumption by the flow-through technique. We measured oxygen consumption in rats during incremental exercise and found a mean maximum value of 94 +/- 13 ml . kg-1 . min-1. The treadmill is simple and inexpensive to construct and is reliable in performance.
Role of intercostal muscles in the rib cage distortions produced by inspiratory loads
Authors: Sampson M. G. , De Troyer A.
Published: December 2017

We studied the patterns of rib cage (RC) deformation in six normal subjects breathing against different resistive and elastic inspiratory loads, and we examined, with concentric needle electrodes, the role played by the inspiratory intercostal muscles in the development of these patterns. Four of the subjects deformed their RC to a more elliptical shape during loaded inspirations; RC anteroposterior diameter became smaller and RC lateral diameter became larger. The RC deformation increased as the load increased, but it appeared to be independent of the nature of the load. Moreover these deformations were associated with a marked increase in the inspiratory activity of the intercostals situated in the lateral parts of the RC and a striking diminution of the activity in the parasternal area. On the other hand, two subjects invariably breathed along their RC relaxation characteristic, and they showed an increased inspiratory activity in all regions of the intercostal musculature. These findings indicate that 1) the pattern of RC deformation during loaded inspirations is closely related to the activity and coordination of the various inspiratory intercostal muscles, and 2) the parasternal intercostals are not necessarily representative of all the inspiratory intercostals. They are also strong evidence against the concept that the parasternal intercostal electrical activity normally recorded during quiet breathing is an excitatory reflex activity.
Coronary collateral stimulation by exercise in dogs with stenotic coronary arteries
Authors: Cohen M. V. , Yipintsoi T. , Scheuer J.
Published: December 2017

To determine the effects of an exercise-training program on coronary collateral development, we instrumented 13 1-yr-old beagles with left circumflex (LCf) coronary artery flow probes and balloon occluders and left atrial and aortic catheters. The LCf artery was constricted resulting in a 58 +/- 4% reduction of the peak reactive hyperemia response following release of a 154-s LCf occlusion. All dogs were studied during the first week of the study protocol. Resting heart rate, cardiac output, and left atrial and aortic pressures were evaluated before and during a 1-min LCf occlusion. Myocardial blood flow was also measured with radioactively-labeled microspheres injected into the left atrium during the LCf occlusion. Subsequently the dogs were exercised at 6.4 km/h and 12% grade, and all hemodynamic and blood flow measurements were repeated. The animals were then randomized to either a sedentary or exercising group. The six sedentary animals were confined to their cages, while the seven training beagles did sprint and endurance running for 75 min/day, 5 days/wk. After 12 wk the hemodynamic and blood flow studies were repeated at rest and during treadmill running. There were no statistically significant differences in resting or exercise hemodynamics, response to LCf occlusion, or myocardial blood flow in the two groups in wk 1. Hemodynamics and blood flow data were virtually unchanged in the sedentary animals after 12 wk. However, the trained dogs demonstrated less evidence of left ventricular failure following LCf occlusion while running and had significantly higher myocardial blood flows. Their resting collateral flow increased from 0.52 +/- 0.16 ml . min-1 . g-1 at wk 1 to 0.90 +/- 0.28 ml . min-1 . g-1 at wk 12 (P less than 0.05), while the ratio of collateral to normal myocardial blood flow increased from 0.46 +/- 0.12 to 0.64 +/- 0.16 (P less than 0.05). Thus chronic exercise can stimulate coronary collateral development, and the enhanced collateral flow has a salutary functional effect.
Partitioning of pulmonary vascular resistance in dogs by arterial and venous occlusion
Authors: Hakim T. S. , Michel R. P. , Chang H. K.
Published: December 2017

We perfused in situ isolated left lower lung lobes at a steady flow rate in zone 3 condition. When the lobar arterial inflow was suddenly occluded, the arterial pressure (Pa) fell rapidly and then more slowly. When the lobar venous outflow was suddenly occluded, the venous pressure (Pv) rose rapidly and then continued to rise more slowly. The rapid changes in Pa and Pv with inflow and outflow occlusion, respectively, represent the pressure drops across the arterial (delta Pa) and venous (delta Pv) relatively indistensible vessels. The total arteriovenous pressure difference (delta Pt) minus delta Pa + delta Pv gives the pressure drop across the vessels in the middle (delta Pm) that are much more distensible. Serotonin and histamine infusion increased delta Pa and delta Pv, respectively, but left delta Pm unchanged. delta Pa and delta Pv, but not delta Pm, increased as flow rate was increased. The studies with varying flow rate and venous pressures suggested that the arteries and veins became resistant to distension when their transmural pressures exceeded 10--5 Torr, respectively. Under the conditions studied, the middle nonmuscular segment contributed a major fraction of the vascular compliance and less than 16% of the total resistance. The muscular arteries and veins contributed equally to the remaining resistance. We conclude that the arterial and venous occlusion method is a useful technique to describe the resistance and compliance of different segments of the pulmonary vasculature.
Influence of panting frequency on plethysmographic measurements of thoracic gas volume
Authors: Bohadana A. B. , Peslin R. , Hannhart B. , Teculescu D.
Published: December 2017

Using an integrated flow pressure-corrected body plethysmograph we obtained total lung capacities (TLC) derived from thoracic gas volumes measured at low, medium, and high panting frequencies in 10 healthy men and in 13 patients with chronic airflow obstruction before and after an aerosol of albuterol. Using a gastric balloon we also assessed gastric-to-mouth pressure ratios (delta Pga/delta Pm). In patients before albuterol, estimated TLC remained unchanged from low to medium and increased (not significantly) from medium to high frequency. Healthy subjects and patients after albuterol showed a significant decrease in TLC from low to medium panting frequencies, which persisted after correcting the data for abdominal gas compression using observed delta Pga/delta Pm. In patients after albuterol the results may be explained, at least in part, by intrathoracic airway compliance and mechanical inhomogeneity of the lung. In healthy subjects a remote possibility is the association of mechanical inhomogeneity and nonuniform pleural pressure.
Instrumentation simultaneously measuring VCO2 and VO2 in humans using titration methods
Authors: Tsoi C. M. , Raemer D. B. , Westenskow D. R.
Published: December 2017

An instrument has been developed for the simultaneous measurement of carbon dioxide excretion (VCO2) and oxygen uptake (VO2). This instrument, the Nutrimeter, gives these breath-averaged measurements continuously without having to determine respiratory flow rate, perform timed spirometric gas collections, or determine absolute CO2 or O2 concentrations. It can be used on ventilated or nonventilated patients in long- and short-term studies. VO2 is determined via the replenishment technique. VCO2 is determined via a new technique, absorption-titration, described here. Bench test results of VCO2 measurements show a standard error of the estimate (SEE) +/- 0.591% of full scale (500 ml/min) and maximum single point error (MSPE) of +/- 3.54% over a 100--350 ml/min range. VO2 measurements show SEE +/- 0.518% of full scale (1,000 ml/min) and MSPE +/- 2.42% over a 100--450 ml/min range. In 31 human clinical trials the Nutrimeter was compared with the open-circuit spirometric collection and micro-Scholander analysis technique. VCO2 measurements show SEE +/- 2.208% and MSPE +/- 10.57% over 135--315 ml/min. VO2 measurements show SEE +/- 1.134% of full scale and MSPE +/- 9.54% over 170--360 ml/min. Response time is 60 s optimally for step changes in VO2 (0--90% of steady-state value), 90 s for VCO2.
Effects of acute and chronic exposure to nicotine aerosol on bronchial reactivity to inhaled methacholine
Authors: Wallis T. W. , Rogers W. R. , Johanson W. G.
Published: December 2017

Normal baboons, like humans, demonstrate a wide range of bronchial reactivity to inhaled methacholine. Cigarette-smoking baboons demonstrate reduced bronchial reactivity to inhaled methacholine compared with sham-smoking controls after 6 pack-yr of smoking. To evaluate the role of nicotine in this blunting of airway reactivity, we studied the effects of both acute and chronic nicotine inhalation on reactivity to methacholine in baboons. Inhalation of 2 mg of nicotine had no acute effect on lung function but blunted bronchial reactivity in highly reactive animals. This effect was not diminished after daily inhalation of nicotine for 90 days. Marked interindividual differences in bronchial reactivity to methacholine were not abolished by propranolol, suggesting that factors other than beta-adrenergic tone account for this intersubject variability.
Sparing effect of chronic high-altitude exposure on muscle glycogen utilization
Authors: Young A. J. , Evans W. J. , Cymerman A. , Pandolf K. B. , Knapik J. J. , Maher J. T.
Published: December 2017

Substrate utilization during heavy [approximately 85% maximum O2 consumption (VO2max)] bicycle exercise was examined in eight low-altitude residents at sea level (SL) and after acute (2 h) and chronic (18 days) high-altitude (HA) exposure at 4,300 m. Mean VO2max was approximately 27% lower at acute HA than at SL and did not change significantly with continued HA exposure. Biopsies from the vastus lateralis muscle and venous blood samples were obtained before and after 30 min of exercise, whereas determinations of the respiratory exchange ratio (R) were made at 10-min intervals during each of the submaximal bouts. Resting levels of serum-free fatty acids at acute and chronic HA were, respectively, two and three times higher than SL but were unchanged with exercise. Exercise did not alter resting serum glycerol levels at SL or during acute HA, but during chronic HA resting glycerol levels were increased 11-fold. Although mean blood lactate concentrations following exercise at SL and acute HA were not significantly different, postexercise lactate concentrations were 87% lower after chronic HA. During exercise at SL and acute HA, muscle glycogen utilization and R were not different. At chronic HA, muscle glycogen utilization and R were 41 and 15% lower, respectively. These data suggest that after chronic HA exposure, increased mobilization and use of free fatty acids during exercise resulted in sparing of muscle glycogen.
Time course of ultrastructural changes in skeletal muscle after two types of exercise
Authors: Nimmo M. A. , Snow D. H.
Published: December 2017

To ascertain the effects of sprint and endurance exercise on the time course of skeletal muscle mitochondrial changes, an ultrastructural study was conducted on four Thoroughbred horses. Skeletal muscle biopsies were taken at various intervals during and after the exercise. Transient mitochondrial alterations of varying degrees were observed following both types of exercise and were considered to be related to the development of fatigue. The degree of distortion of mitochondrial structure is considered not to represent the in vivo condition but the state of responsiveness to the fixation medium.
Effect of baroreceptor reflex stimulation on blood flow to an atelectatic lung
Authors: Strawn W. B. , Hall S. M. , Levitzky M. G.
Published: December 2017

The effect of baroreceptor reflex stimulation by carotid sinus hypotension on the pulmonary vascular response to atelectasis was studied in eight dogs anesthetized with chloralose. Closed-chest dogs with electromagnetic flow probes previously implanted on their left (QL) and main (QT) pulmonary arteries had their left and right lungs ventilated separately. Their carotid sinuses were isolated bilaterally and perfused by a pulsatile pump with a physiological salt solution. After an initial period of bilateral 100% O2 ventilation with carotid sinus perfusion pressures (CSPP) set at each animal's initial mean arterial pressure (98 +/- 19 Torr), the left airway was occluded, QL/QT fell from 0.33 +/- 0.01 to 0.24 +/- 0.02 and PO2 fell from 323 +/- 35 Torr to 74 + 7 Torr. When CSPP was lowered to 21 +/- 3 Torr, there were no changes in QL/QT and PO2. These results suggest that stimulation of the baroreceptor reflex by carotid sinus hypotension does not interfere with the diversion of pulmonary blood flow away from a unilaterally atelectatic lung.
Effect of training on beta-adrenergic receptor number in rat heart
Authors: Moore R. L. , Riedy M. , Gollnick P. D.
Published: December 2017

Female Sprague-Dawley rats were subjected to endurance-training programs, and the effect of training on myocardial beta-adrenergic receptor number, receptor-binding characteristics, and adenylate cyclase (AC) activities associated with the receptor were examined. Training produced a 45% (P less than 0.01) increase in the succinate dehydrogenase activity of the plantaris muscle. Specific (-)-[3H]dihydroalprenolol (DHA)-binding data were subjected to Scatchard plot analysis to quantify beta-adrenergic receptor number and DHA-binding characteristics of myocardial membranes. The DHA concentrations at which 50% of the total binding sites were occupied were similar for membranes from sedentary (1.95 +/- 0.51) and trained (1.59 +/- 0.34 nM) groups. Total DHA-binding sites of membranes from control (91.6 +/- 13.3) and trained (83.1 +/- 7.6 fmol/mg) groups were also similar. Basal and maximally stimulated AC activities were also unchanged by endurance training. Fluoride-stimulated AC activities of crude homogenate and 10,000 g fractions decreased 47 and 49%, respectively, with training. No differences were observed in a 40,000 g fraction. The specific activities of a ouabain-sensitive Na+-K+-ATPase (a sarcolemmal membrane marker) of crude homogenate, 10,000 g, and 40,000 g membrane fractions were similar. These data indicate that training produces no detectable difference in the potential for adrenergic responses at the receptor level.
Reflex stimulation of tracheal mucus gland secretion by gastric irritation in cats
Authors: German V. F. , Corrales R. , Ueki I. F. , Nadel J. A.
Published: December 2017

Our aim was to determine whether flow from the submucosal glands of the trachea is reflexly regulated by sensory stimuli from the stomach in the cat, and, if such a gastropulmonary reflex exists, what sensory and motor pathways are important. We found that mechanical stimulation of the gastric mucosa increased submucosal gland secretions from 7.9 +/- 0.7 to 17.4 +/- 1.7 nl/min (mean +/- SE, P less than 0.001). This effect was prevented reversibly by cooling both abdominal vagus nerves to -3 degrees C before stimulation and was restored by rewarming the nerves. The effect was prevented irreversibly by cutting both abdominal vagus nerves and was then mimicked by electrically stimulating the central cut end of one of the nerves. This increase in secretions caused by electrical stimulation of the nerve was prevented by administration of atropine sulfate before stimulation. We conclude that stimuli from the stomach reflexly affect the rate of submucosal gland secretion. The sensory limb of this reflex lies in the abdominal vagus nerves, and the motor pathways are mediated by cholinergic muscarinic receptors.
Finger temperature after a finger-cooling test: influence of air temperature and smoking
Authors: Cleophas T. J. , Fennis J. F. , van't Laar A.
Published: December 2017

Skin temperature of one finger was measured before and after immersion of the gloved fingers of both hands in 16 degrees C water for 5 min [room temperature (Ta) 24 or 20 degrees C]. At Ta 24 degrees C, 23 of 25 normal nonsmokers (92%) had finger rewarming to above 24 degrees C in 12 min after cold immersion, at Ta 20 degrees C, only 1 of 12 (8%) had similar rewarming. Among 12 habitual smokers only 4 (33%) rewarmed above 24 degrees C (Ta 24 degrees C) following a 1-h abstinence from smoking, but 8 (67%) did so after a 24-h abstinence. Only 2 of these 8, however, did so in a retest 10 min after smoking a cigarette. The smokers were not tested at Ta 20 degrees C. We conclude that air temperature and cigarette smoking are important determinants of finger rewarming following a finger-cooling test.
Evidence for pulmonary CO2 chemosensitivity: effects on ventilation
Authors: Sheldon M. I. , Green J. F.
Published: December 2017

To determine whether there is a pulmonary chemoreceptor for CO2 that influences spontaneous ventilation (VE), we separated the systemic and pulmonary circulations and controlled partial pressure of CO2 (PCO2) independently in each circuit under hyperoxic conditions and measured VE. Dogs were anesthetized with ketamine and maintained with 1% halothane. Systemic venous return was drained from the right atrium and passed through an oxygenator and heat exchanger; blood was returned to the ascending aorta. An identical bypass was established for the pulmonary circulation, draining blood from the left atrium and returning it to the pulmonary artery. The heart was fibrillated; all cannulas were brought through the chest wall; and the median sternotomy was closed. Blood flow through both circuits was maintained at 0.080 l . kg-1 . min-1. Systemic PCO2 (PSCO2) was held constant at three different nonoscillatory levels. At each level, pulmonary PCO2 (PpCO2) was randomly varied between approximately 7 and 85 Torr. With PSCO2 at 43.5 +/- 0.4 Torr, VE increased 2.67 +/- 0.61 l . min-1 as PpCO2 was varied between these limits. With PSCO2 at 63.8 +/- 2.5 Torr, VE increased 3.95 +/- 0.73 l . min-1 over these same limits of PpCO2. With PSCO2 below 25--30 Torr, the dogs were apneic and no longer responded to changes in PpCO2. The effect of PpCO2 on VE was abolished by vagotomy. These results suggest the presence of a CO2 chemoreceptor in the lung that interacts with the nonpulmonary chemoreceptors in the control of VE.
Role of the carotid body in hyperpnea of moderate exercise in goats
Authors: Bisgard G. E. , Forster H. V. , Mesina J. , Sarazin R. G.
Published: December 2017

In the present study the ventilatory response to exercise was measured in goats before and after carotid body excision (CBE) (n = 7) or sham operation (n = 1). Nine-minute periods of moderate treadmill walking were carried out under three conditions: 4.8 kph, 0% grade during normoxia and hypoxia (arterial O2 tension approximately 43 Torr) and 4.8 kph, 5% grade during normoxia. Ventilatory variables, metabolic rate, and arterial blood acid-base and blood gases were measured at 30-s intervals for the first 3 min and again during the 6th and 9th min of exercise. In normal goats during exercise in normoxia, ventilation changed in proportion to changes in metabolic rate resulting in arterial CO2 tension (PaCO2) and arterial pH (pHa) homeostasis throughout exercise. CBE resulted in nearly equivalent hypoventilation during steady-state rest and exercise (delta PaCO2 approximately equal to 5--7 Torr) during normoxia and loss of the positive interaction between hypoxia and exercise. There was also a significant disruption of PaCO2-pHa homeostasis during the first 30 s of exercise after CBE when PaCO2 was 3 Torr below rest and pHa was 0.03 units above rest. Our data indicate: 1) that the carotid chemoreceptors may contribute a similar proportional drive to breathe during rest and exercise; 2) that transient hyperventilation at the onset of exercise after CBE may indicate an important neural drive to breathe that is normally damped by intact peripheral chemoreceptors; and 3) that the mechanism linking ventilation to CO2 production remains intact after CBE.
Single-breath method for measurement of respiratory mechanics in anesthetized animals
Authors: Zin W. A. , Pengelly L. D. , Milic-Emili J.
Published: December 2017

In six spontaneously breathing anesthetized cats (pentobarbital sodium, 35 mg/kg ip) airflow, changes in lung volume and tracheal pressure were measured. The airways were occluded at end inspiration (VT). During the ensuing period of apnea (Breuer-Hering inflation reflex), the animal relaxed the respiratory muscles and the passive compliance of the respiratory system (Crs) was computed by dividing VT by the tracheal pressure. While the animal was still relaxed, the airways were reopened, and during the ensuing relaxed expiration the volume-flow relationship was linear, the slope representing the time constant of the respiratory system: tau rs = Crs . Rrs, where Rrs is the flow resistance of the passive respiratory system. From the measured values of tau rs and Crs, Rrs was computed. With this information it was also possible to quantitate the antagonistic pressure developed by the inspiratory muscles during spontaneous expiration.
Propranolol-vagal-alveolar CO2 interactions on collateral gas flow in dog lungs
Authors: Olson L. E. , Robinson N. E.
Published: December 2017

The mechanical properties of a collaterally ventilating lung segment were studied in 18 anesthetized paralyzed mongrel dogs artificially ventilated with room air end-tidal CO2 fraction = 5%. Nine dogs were pretreated with propranolol, and nine dogs were not. With 0, 5, or 12% CO2 in O2 flowing into the segment, steady-state resistance of segmental airways (Rss) and time for 90% pressure equilibration (T90) between the segment and airway opening after flow was discontinued were determined at functional residual capacity with the vagus nerve ipsilateral to the segment intact, sectioned, or electrically stimulated. Vagal stimulation increased Rss and T90 at all CO2 levels, whereas unilateral vagotomy had no effect. Propranolol treatment enhanced the increase in Rss caused by vagal stimulation at low but not at high CO2 levels, suggesting that high CO2 mimics the effect of propranolol on Rss. High levels of CO2 did not have the same effect as propranolol on T90, propranolol treatment reducing the increase in T90 caused by vagal stimulation at high but not at low CO2 levels. These results demonstrate that local changes in alveolar CO2 tensions modify but do not abolish the effect of vagal stimulation on collateral ventilation.
Alae nasi activation and nasal resistance in healthy subjects
Authors: Strohl K. P. , O'Cain C. F. , Slutsky A. S.
Published: December 2017

To investigate the effect of alae nasi (AN) activation on nasal resistance, we monitored AN electromyographic (EMG) activity in 17 healthy subjects using surface electrodes placed on either side of the external nares and measured inspiratory nasal resistance utilizing the method of posterior rhinometry. With CO2 inhalation (6 subj), AN EMG activity increased as nasal resistance fell 23 +/- 5% (P less than 0.01). In the same subjects, voluntary flaring of the external nares also increased AN EMG and decreased nasal resistance by 29 +/- 5% (P less than 0.01). Nasal resistance was altered by nasal flaring and CO2 inhalation even after administration of a topical nasal vasoconstrictive spray (8 subj). In six subjects, voluntary nasal flaring or inhibition with the mouth closed produced a 21 +/- 12% change (P less than 0.01) in total airway resistance as measured by body plethysmography. We conclude that activation of the alae nasi will decrease nasal and total airway resistance during voluntary nasal flaring and during CO2 inhalation and thus should be considered in any studies of upper airway resistance.
Regional diffusing capacity in normal lungs during a slow exhalation
Authors: MacIntyre N. R. , Nadel J. A.
Published: December 2017

From an analysis of carbon monoxide uptake and xenon-133 distribution after two bolus inhalations of these gases, we calculated regional diffusing capacity in the upper and lower volume halves of the lungs during the middle 60% of an exhaled vital capacity in five seated normal subjects. We found that the regional diffusing capacity of the upper half of the lungs was 11.6 +/- 4.2 (mean +/- SD) ml.min-1.Torr-1 and that the regional diffusing capacity of the lower half of the lungs was 24.4 +/- 2.4 ml.min-1.Torr-1 after 25% of the vital capacity had been exhaled. These values remained relatively constant as lung volume decreased from 25 to 75% of the exhaled vital capacity. Diffusing capacity in the upper half of the lungs ranged from 9.4 to 12.4 ml.min-1.Torr-1 during exhalation, and in the lower half of the lungs from 21.0 to 28.6 ml.min-1.Torr-1 during exhalation. These results suggest that total lung diffusing capacity remains relatively constant over this midrange of lung volumes and that this occurs because the regional diffusing capacities in both the upper and lower halves of the lungs remain relatively constant.
Measurement of lung water in dog lobes using inhaled C15O2 and injected H215O
Authors: Swinburne A. J. , MacArthur C. G. , Rhodes C. G. , Heather J. D. , Hughes J. M.
Published: December 2017

Indicator-dilution analysis was used in a recirculation-free isolated dog lobe preparation to compare an inhaled water tracer (C15O2) and an injected water tracer (H215O) with direct weighing as a measure of total lung water. Residue detection (counting over the lung) was compared with outflow detection (counting over the venous effluent). With outflow detection, inhaled C15O2 measured 74% and injected H215O 90% of the gravimetric lung water. In hemodynamic edema, the increase in lung water measured by residue detection of both tracers correlated well with increases in weight (r = 0.92, slope = 1.03). However, outflow detection of both tracers underestimated the lung water increase by 53% in edema (r = 0.88, slope = 0.47). Thus, in edema, equilibration of both tracers within the lung water volume is rapid, but clearance from the lung is delayed because slowly clearing water pools develop. The errors caused by inhomogeneity of perfusion distribution were investigated after pulmonary arterial injection of 34-, 50-, and 175-micrometers spheres. For the same lung weight, C15O2 transit was delayed and H215O transit accelerated greatly by the 175-micrometers spheres and slightly by the 50-micrometers spheres.
Evidence for diminished sensitivity of the hamster pulmonary vasculature to hypoxia
Authors: Walker B. R. , Voelkel N. F. , McMurtry I. F. , Adams E. M.
Published: December 2017

Many mammals exhibit elevated pulmonary arterial pressure when exposed to airway hypoxia. In addition, prolonged hypoxic exposure may result in elevated hematocrit and right ventricular hypertrophy. The current study was designed to test whether the hamster, a fossorial species, may possess naturally selected physiological characteristics advantageous to a chronically hypoxic environment. Hamsters and rats were studied at low altitude (1,520 m) and after 5 wk at high altitude (4,250 m). Hematocrit for low-altitude hamsters was 53 +/- 1 compared with 45 +/- 1 for low-altitude rats. Low-altitude hamsters and rats demonstrated the same right ventricular weight-to-total ventricular weight ratio (RV/T) (0.223 +/- 0.006 vs. 0.222 +/- 0.003). After high-altitude exposure the hematocrit for hamsters and rats was the same (58 +/- 1 vs. 57 +/- 1), but RV/T was less in the hamster (0.251 +/- 0.004 vs. 0.288 +/- 0.005). In addition, the hypoxic pulmonary pressor response of lungs isolated from low- and high-altitude animals was examined. Lungs from hamsters were less responsive than lungs from rats at all levels of hypoxia tested. In addition, exposure to altitude resulted in a diminished pressor response in lungs from both species. It is concluded that the pulmonary vasculature of the hamster is less responsive to hypoxia than that of the rat, and that this relative unresponsiveness may aid the hamster in an hypoxic environment.
Intrapulmonary blood flow redistribution during hypoxia increases gas exchange surface area
Authors: Capen R. L. , Wagner W. W.
Published: December 2017

We have previously shown that airway hypoxia causes pulmonary capillary recruitment and raises diffusing capacity for carbon monoxide. This study was designed to determine whether these events were caused by an increase in pulmonary vascular resistance, which redistributed blood flow toward the top of the lung, or by an increase in cardiac output. We measured capillary recruitment at the top of the dog lung by in vivo microscopy, gas exchange surface area of the whole lung by diffusing capacity for carbon monoxide, and blood flow distribution by radioactive microspheres. During airway hypoxia recruitment occurred, diffusing capacity increased, and blood flow was redistributed upward. When a vasodilator was infused while holding hypoxia constant, these effects were reversed; i. e., capillary “derecruitment” occurred, diffusing capacity decreased, and blood flow was redistributed back toward the bottom of the lung. The vasodilator was infused at a rate that left hypoxic cardiac output unchanged. These data show that widespread capillary recruitment during hypoxia is caused by increased vascular resistance and the resulting upward blood flow redistribution.
Effect of changing lung mass on lung water and permeability-surface area in sheep
Authors: Snapper J. R. , Harris T. R. , Brigham K. L.
Published: December 2017

The effects of changing cardiac output and lung mass on pulmonary capillary surface area, lung water, and hemodynamics were studied in eight sheep. 51Cr-erythrocytes, 125I-albumin, 3H2O, and [14C]urea were injected into the right atrium, and timed samples were collected from the aorta for the calculation of cardiac output (CO), extravascular lung water (EVLW), and permeability-surface area product (PS) for [14C]urea. CO was varied by opening and closing arteriovenous shunts, and lung mass was decreased by first tying off the left lung followed by tying off the right lower lobe. Pulmonary arterial pressure (r = -0.741) and pulmonary vascular resistance (r = -0.700) increased as lung mass was decreased. CO decreased slightly (r = -0.470 while left atrial pressure was not changed (r = -0.144) by decreasing lung mass. There was a close correlation between EVLW and lung mass (r = 0.944) and between [14C]urea PS and lung mass (r = 0.672). We were able to demonstrate that [14C]urea behaves as a diffusion-limited tracer in a single pass through the lungs, since [14C]urea extraction decreased as flow per unit mass increased. These results support the clinical use of multiple-tracer studies to measure EVLW and [14C]urea PS.