bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of inspiratory assistance on ventilatory control during moderate exercise
Authors: Poon C. S. , Ward S. A. , Whipp B. J.
Published: December 2017

In five healthy subjects, we studied the effects of controlled mechanical unloading of the respiratory system on ventilatory control during moderate exercise, utilizing a modified positive-pressure ventilator (IEEE Trans. Biomed. Eng. BME-33: 361–365, 1986). We were especially interested in whether isocapnia was maintained when a portion of the normal ventilatory response to constant-load cycling was subserved by the ventilator. The mechanical unloading was achieved by “assisting” airflow throughout inspiration in a constant proportion to instantaneous flow. Two modest degrees of assistance (A1 = 1.5 and A2 = 3.0 cmH2O X l-1 X s) were imposed. The assistance caused minute ventilation (VE) to increase immediately (inspiratory time shortening and tidal volume rising) and end-tidal PCO2 (PETCO2) to fall. Some 10–15 s later, inspiratory occlusion pressure (P100) decreased, and in the new steady-state VE and PETCO2 were virtually restored to their control exercise levels. The modest residual hyperventilation [delta PETCO2 = -0.9 Torr (A1) and -1.6 Torr (A2)], which was not significant statistically, contrasted markedly with the much larger increase predicted for VE had there been no compensatory reduction in ventilatory drive (as evidenced by the fall in P100). Consistent with earlier studies utilizing resistive loading (J. Appl. Physiol. 35: 361–366, 1973 and Acta Physiol. Scand. 120: 557–565, 1984), these observations suggest that ventilatory drive during moderate exercise is controlled to compensate for modest changes in respiratory-mechanical load, so that VE is preserved at a level appropriate to metabolic rate or nearly so.
Maximal vascular leg conductance in trained and untrained men
Authors: Snell P. G. , Martin W. H. , Buckey J. C. , Blomqvist C. G.
Published: December 2017

Lower leg blood flow and vascular conductance were studied and related to maximal oxygen uptake in 15 sedentary men (28.5 +/- 1.2 yr, mean +/- SE) and 11 endurance-trained men (30.5 +/- 2.0 yr). Blood flows were obtained at rest and during reactive hyperemia produced by ischemic exercise to fatigue. Vascular conductance was computed from blood flow measured by venous occlusion plethysmography, and mean arterial blood pressure was determined by auscultation of the brachial artery. Resting blood flow and mean arterial pressure were similar in both groups (combined mean, 3.0 ml X min-1 X 100 ml-1 and 88.2 mmHg). After ischemic exercise, blood flows were 29- and 19-fold higher (P less than 0.001) than rest in trained (83.3 +/- 3.8 ml X min-1 X 100 ml-1) and sedentary subjects (61.5 +/- 2.3 ml X min-1 X 100 ml-1), respectively. Blood pressure and heart rate were only slightly elevated in both groups. Maximal vascular conductance was significantly higher (P less than 0.001) in the trained compared with the sedentary subjects. The correlation coefficients for maximal oxygen uptake vs. vascular conductance were 0.81 (trained) and 0.45 (sedentary). These data suggest that physical training increases the capacity for vasodilation in active limbs and also enables the trained individual to utilize a larger fraction of maximal vascular conductance than the sedentary subject.
Unaltered norepinephrine-heart rate relationship in exercise with exogenous heat
Authors: Rowell L. B. , Brengelmann G. L. , Freund P. R.
Published: December 2017

We measured plasma norepinephrine (NE) concentration, an index of sympathetic nervous activity, and epinephrine (E), an index of adrenal medulla activity, in six normal young men during mild to severe exercise, with and without superimposed heat stress. The primary objective was to observe whether the normally close relationship between heart rate and log NE concentration in upset when heart rate at a given work load is increased by heat stress. Exercise, beginning at 50 W, was graded in 50-W increments lasting 10 min each up to 200 W, which lasted 5–10 min. Each subject went through the protocol twice, once with skin temperature kept low by a water-perfused suit and then with skin temperature raised to 38 degrees C. Exogenous heart stress raised log circulating NE concentration in proportion to the rise in heart rate at a given work load so that the usual relationship between these variables, previously observed during other stresses, was preserved. In contrast to some other stresses, heat stress had no added effect on E concentration, indicating that this stress during exercise raises sympathetic neural activity (as reflected in the rise in NE) without stimulating additional adrenal release of E.
Physiological factors affecting O2 transport by hemoglobin in an in vitro capillary system
Authors: Lemon D. D. , Nair P. K. , Boland E. J. , Olson J. S. , Hellums J. D.
Published: December 2017

O2 transport was examined by measuring the fractional saturation of concentrated hemoglobin solutions flowing through an artificial capillary that was approximately 27 micron in diameter and embedded in a silicone rubber film approximately 170 micron thick. The effects of pH, hemoglobin concentration, O2 tension, temperature, and organic phosphate were measured and analyzed quantitatively by a rigorous mathematical model that included the geometry of the capillary in the silicone film, parabolic flow velocity distributions inside the lumen, and cooperative O2 binding by hemoglobin. The rates of both oxygenation and deoxygenation were limited by diffusion and governed by the magnitude of the O2 gradient between the intracapillary fluid phase and the external gas space. In uptake experiments, O2 flux is determined primarily by the external O2 tension (16–160 mmHg in our experiments) because the internal O2 pressure is kept small due to chemical combination with hemoglobin. In release experiments, the external O2 tension is maintained at zero, and the transport rate is determined by the intracapillary partial pressure of O2 that is proportional to the O2 half-saturation pressure of hemoglobin value of the hemoglobin sample. As a result, factors that change the affinity of hemoglobin for O2, such as pH, temperature, and organic phosphate concentration, influence strongly the rate of O2 release but have little effect on the rate of O2 uptake. These properties are physiologically advantageous, since a decrease in pH or an increase in temperature during exercise increases both the rate and extent of deoxygenation while not altering the kinetics of oxygenation.
Severe pulmonary hypertension and arterial adventitial changes in newborn calves at 4,300 m
Authors: Stenmark K. R. , Fasules J. , Hyde D. M. , Voelkel N. F. , Henson J. , Tucker A. , Wilson H. , Reeves J. T.
Published: December 2017

Some human newborns have a syndrome characterized by irreversible pulmonary hypertension and severe hypoxemia and by medial hypertrophy and adventitial thickening of pulmonary arteries. We considered that newborn calves made severely hypoxic might reproduce features of the human disease. When 2-day-old calves were placed at 4,300 m simulated altitude, pulmonary arterial pressure was increased and could be reversed by 100% O2. However, after 2 wk at 4,300 m, pulmonary arterial pressures were suprasystemic and there was right-to-left shunting probably through the foramen ovale and a patent but restrictive ductus arteriosus. Suprasystemic pulmonary pressure and hypoxemia persisted with 100% O2 breathing. Morphometrical examination of the lung arteries showed a markedly thickened adventitia with cellular proliferation and collagen and elastin deposition. There was increased medial thickness and distal muscularization of the pulmonary arteries associated with decreased luminal diameter. The rapid development of severe pulmonary hypertension and poor responsiveness to O2 was associated with increased arterial wall thickness, particularly involving the adventitia. Thus the pulmonary arterial circulation in these calves, which were placed at high altitude for 2 wk, exhibited features resembling persistent pulmonary hypertension in newborn infants.
Elevation of superior vena caval pressure increases extravascular lung water after endotoxemia
Authors: Allen S. J. , Drake R. E. , Katz J. , Gabel J. C. , Laine G. A.
Published: December 2017

In many sheep Escherichia coli endotoxin results in pulmonary hypertension, increased microvascular permeability, pulmonary edema, and increased central venous pressure. Since lung lymph drains into the systemic veins, increases in venous pressure may impair lymph flow sufficiently to enhance the accumulation of extravascular fluid. We tested the hypothesis that, following endotoxin, elevating the venous pressure would increase extravascular fluid. Thirteen sheep were chronically instrumented with catheters to monitor left atrial pressure (LAP), pulmonary arterial pressure (PAP), and superior vena caval pressure (SVCP) as well as balloons to elevate LAP and SVCP. These sheep received 4 micrograms/kg endotoxin, and following the pulmonary hypertensive spike the left atrial balloon was inflated so that (PAP + LAP)/2 = colloid osmotic pressure. It was necessary to control PAP + LAP in this way to minimize the sheep-to-sheep differences in the pulmonary hypertension. We elevated the SVCP to 10 or 17 mmHg or allowed it to stay low (3.2 mmHg). After a 3-h period, we killed the sheep and removed the right lungs for determination of the extravascular fluid-to-blood-free dry weight ratio (EVF). Sheep with SVCP elevated to 10 or 17 mmHg had significant increases in EVF (5.2 +/- 0.1 and 5.6 +/- 1.2) compared with the sheep in which we did not elevate SVCP (EVF = 4.5 +/- 0.4). These results indicate that sustained elevation in central venous pressure in patients contributes to the amount of pulmonary edema associated with endotoxemia.
Measurement of albumin permeability across endothelial monolayers in vitro
Authors: Cooper J. A. , Del Vecchio P. J. , Minnear F. L. , Burhop K. E. , Selig W. M. , Garcia J. G. , Malik A. B.
Published: December 2017

We have developed an experimental system to measure the permeability of the cultured endothelial monolayer. The luminal-to-abluminal flux of 125I-albumin across cultured pulmonary endothelium was expressed as a clearance rate equal to the permeability-surface area product. After clearance rate measurement for a 30-min base-line period, a test agent was added to the luminal side, and the clearance rate was remeasured during a 30-min experimental period. In control studies the base-line clearance rate was 0.343 +/- 0.017 microliter/min. After correction for the diffusional resistances of the filter and unstirred layers, the calculated permeability of the endothelial monolayer was 1.2 X 10(-5) cm/s. When culture medium was the test agent, the experimental clearance rate was unchanged from the base-line value. After addition of 4 mM oleic acid to the luminal chamber, the clearance rate was 0.528 +/- 0.017 microliter/min compared with a base-line value of 0.330 +/- 0.008 microliter/min (P less than 0.005). This method allows the calculation of endothelial permeability with correction for unstirred layers and the use of each monolayer as its own control.
Adaptation of the left ventricle to exercise-induced hypertrophy
Authors: White F. C. , McKirnan M. D. , Breisch E. A. , Guth B. D. , Liu Y. M. , Bloor C. M.
Published: December 2017

Cardiac functional and structural adaptations to exercise-induced hypertrophy were studied in 68 pigs. Pigs were exercise trained on a treadmill for 10 wk. Sequential measurements were made of cardiac dimensions, [left ventricular end-diastolic diameter (EDD), changes in diameter (delta D%), wall thickness (WTh), wall thickening (WTh%), left ventricular pressure (LVP), time derivative of pressure (dP/dt), stroke volume, total body O2 consumption (VO2), blood gases, and systemic hemodynamics] at rest and during moderate and severe exercise. Postmortem studies included morphometric measurements of capillary density, arteriolar density, mitochondria, and myofibrils. All of the exercise-trained pigs showed significant increases in aerobic capacity. Maximum O2 consumption (VO2 max) increased by 37.5% in group 1 (moderate exercise training) and 34% in group 3 (heavy exercise training). Cardiac hypertrophy ranged from less than 15% in a group (n = 8) subjected to moderate exercise training to greater than 30% in a group (n = 11) subjected to heavy exercise training. Before training, exercise was characterized by a decreasing EDD during progressive exercise; this was reversed after exercise training. Stroke volume and end-diastolic volumes during exercise showed a highly significant increase after exercise training and hypertrophy. Morphometric measurements showed that mitochondria and cell membranes increased with increasing myocyte growth in all exercise groups, but there was only a partially compensated adaptation of capillary proliferation. Arteriolar number and length increased in all exercise groups. Intrinsic contractility as measured by delta D%, WTh%, or left ventricular dP/dt did not increase with exercise training and in some instances decreased. Therefore, left ventricular adaptation to strenuous exercise in the pig heart is primarily one of changes in left ventricular dimensions and a compensated hypertrophy. Exercise-induced increases in EDD and stroke volume can be accounted for by decreases in peripheral resistance and increased cardiac dimensions.
Arterial occlusion versus isofiltration pulmonary capillary pressures during very high flow
Authors: Bshouty Z. , Ali J. , Younes M.
Published: December 2017

Pressure in the compliant middle segment of the pulmonary vascular bed (PM), as determined by arterial occlusion, was compared with pressure at the filtration site (effective filtration pressure, EFP), determined by the isofiltration technique, at very high (7–10 times normal) pulmonary flow in six in situ perfused canine left upper lobes. At these flow rates inflow and left atrial pressures averaged 41.9 +/- 1.3 and 2.5 +/- 0.5 (SE) mmHg, respectively. PM was 30.9 +/- 1.6 mmHg, and EFP was 32.3 +/- 1.9 mmHg with no significant difference between the two measurements by paired t test. The results indicate that the arterial occlusion technique yields a pressure that is equivalent to EFP even during very high pulmonary blood flow where the longitudinal distribution of resistance is quite different from that obtained during normal flow.
Physiological neutrophil sequestration in the lung: visual evidence for localization in capillaries
Authors: Lien D. C. , Wagner W. W. , Capen R. L. , Haslett C. , Hanson W. L. , Hofmeister S. E. , Henson P. M. , Worthen G. S.
Published: December 2017

Although the lung is known to be a major site of neutrophil margination, the anatomic location of these sequestered cells within the lung is controversial. To determine the site of margination and the kinetics of neutrophil transit through the pulmonary microvasculature, we infused fluorescein isothiocyanate-labeled canine neutrophils into the pulmonary arteries of 10 anesthetized normal dogs and made fluorescence videomicroscopic observations of the subpleural pulmonary microcirculation through a window inserted into the chest wall. The site of fluorescent neutrophil sequestration was exclusively in the pulmonary capillaries with a total of 951 labeled cells impeded in the capillary bed for a minimum of 2 s. No cells were delayed in the arterioles or venules. Transit times of individual neutrophils varied over a wide range from less than 2 s to greater than 20 min with an exponential distribution skewed toward rapid transit times. These observations indicate that neutrophil margination occurs in the pulmonary capillaries with neutrophils impeded for variable periods of time on each pass through the lung. The resulting wide distribution of transit times may determine the dynamic equilibrium between circulating and marginated neutrophils.
Postexercise muscle and liver glycogen metabolism in male and female rats
Authors: Ivey P. A. , Gaesser G. A.
Published: December 2017

Male and female Wistar rats were run for 5 min at 1.7 mph at a 17% grade to determine whether a sex difference exists in the rate of glycogen resynthesis during recovery in fast-twitch red muscle, fast-twitch white muscle, and liver. Rats were killed at one of three time points: immediately after the exercise bout, and at 1 or 4 h later. Males had significantly higher resting muscle glycogen levels (P less than 0.05). Exercise resulted in significant glycogen depletion in both sexes (P less than 0.01). Males utilized approximately 50% more glycogen during the exercise bout than females (P less than 0.05). During the food-restricted 4-h recovery period, muscle glycogen was repleted significantly during the 1st h (P less than 0.05). Liver glycogen was not depleted as a result of the exercise bout, but fell during the first h of recovery (P less than 0.05) and remained low during the subsequent 3 h. The greater glycogen utilization in red and white fast-twitch muscle during exercise by males could represent a true sex difference but could also be attributable in part to the males having performed more work as a result of 20% greater body mass. We conclude that no sex difference was observed in the rates of muscle glycogen repletion after exercise or in liver glycogen metabolism during and after exercise, and rapid postexercise muscle glycogen repletion occurred at a time of accelerated liver glycogen depletion.
Effects of lung volume on maximal methacholine-induced bronchoconstriction in normal humans
Authors: Ding D. J. , Martin J. G. , Macklem P. T.
Published: December 2017

We examined the effects of lung volume on the bronchoconstriction induced by inhaled aerosolized methacholine (MCh) in seven normal subjects. We constructed dose-response curves to MCh, using measurements of inspiratory pulmonary resistance (RL) during tidal breathing at functional residual capacity (FRC) and after a change in end-expiratory lung volume (EEV) to either FRC -0.5 liter (n = 5) or FRC +0.5 liter (n = 2). Aerosols of MCh were generated using a nebulizer with an output of 0.12 ml/min and administered for 2 min in progressively doubling concentrations from 1 to 256 mg/ml. After MCh, RL rose from a base-line value of 2.1 +/- 0.3 cmH2O. 1–1 X s (mean +/- SE; n = 7) to a maximum of 13.9 +/- 1.8. In five of the seven subjects a plateau response to MCh was obtained at FRC. There was no correlation between the concentration of MCh required to double RL and the maximum value of RL. The dose-response relationship to MCh was markedly altered by changing lung volume. The bronchoconstrictor response was enhanced at FRC - 0.5 liter; RL reached a maximum of 39.0 +/- 4.0 cmH2O X 1–1 X s. Conversely, at FRC + 0.5 liter the maximum value of RL was reduced in both subjects from 8.2 and 16.6 to 6.0 and 7.7 cmH2O X 1–1 X s, respectively. We conclude that lung volume is a major determinant of the bronchoconstrictor response to MCh in normal subjects. We suggest that changes in lung volume act to alter the forces of interdependence between airways and parenchyma that oppose airway smooth muscle contraction.
Triangularis sterni muscle use in supine humans
Authors: De Troyer A. , Ninane V. , Gilmartin J. J. , Lemerre C. , Estenne M.
Published: December 2017

The electrical activity of the triangularis sterni (transversus thoracis) muscle was studied in supine humans during resting breathing and a variety of respiratory and nonrespiratory maneuvers known to bring the abdominal muscles into action. Twelve normal subjects, of whom seven were uninformed and untrained, were investigated. The electromyogram of the triangularis sterni was recorded using a concentric needle electrode, and it was compared with the electromyograms of the abdominal (external oblique and rectus abdominis) muscles. The triangularis sterni was usually silent during resting breathing. In contrast, the muscle was invariably activated during expiration from functional residual capacity, expulsive maneuvers, “belly-in” isovolume maneuvers, static head flexion and trunk rotation, and spontaneous events such as speech, coughing, and laughter. When three trained subjects expired voluntarily with considerable recruitment of the triangularis sterni and no abdominal muscle activity, rib cage volume decreased and abdominal volume increased. These results indicate that unlike in the dog, spontaneous quiet expiration in supine humans is essentially a passive process; the human triangularis sterni, however, is a primary muscle of expiration; and its neural activation is largely coupled with that of the abdominals. The triangularis sterni probably contributes to the deflation of the rib cage during active expiration.
Mucus clearance by two-phase gas-liquid flow mechanism: asymmetric periodic flow model
Authors: Kim C. S. , Iglesias A. J. , Sackner M. A.
Published: December 2017

Mucus transport by two-phase gas-liquid flow mechanism was investigated with in vitro flow models under asymmetric periodic airflow conditions with nine different liquid solutions with rheological properties similar to human sputum. The flow model was made with 1.0-cm-ID glass tube and positioned either vertically or horizontally. With a constant supply of the test liquids into the model tube (0.5 ml/min), the liquid layer transport speed (LLTS) as well as the mean liquid layer thickness at steady-state condition (hs) was measured in conjunction with various airflow patterns of different expiratory and inspiratory flow rate, breathing frequency (f), and tidal volume (VT). The flow patterns were maintained within the range of normal breathing. In the horizontal tube model, LLTS ranged from 1.14 +/- 0.02 to 3.39 +/- 0.04 cm/min at the peak expiratory flow rate (VEp) of 30–60 l/min. The inspiratory flow rate, as well as f and VT did not affect LLTS. However, LLTS increased with increasing VEp, and at the same VEp LLTS was higher with viscoelastic than with viscous liquid. In the vertical tube model, the upward transport of mucus could not be achieved at VEp lower than 30 l/min particularly with low viscosity and low elasticity fluid. However, at high values of VEp, LLTS was comparable to that in the horizontal tube model with viscoelastic fluid, whereas LLTS of viscous liquid showed 26–40% lower than that in the horizontal tube model. The value of hs was 5–20% of the tube diameter at VEp of 30–60 l/min in both models. These results indicate that effective mucus clearance can be achieved by two-phase gas-liquid flow mechanism in patients with excessive bronchial secretions with biased tidal breathing favoring the expiratory flow and that the clearance can be further promoted by changing rheological properties of mucus.
Role of intracellular pH in muscle fatigue
Authors: Metzger J. M. , Fitts R. H.
Published: December 2017

Intracellular pH of in vitro diaphragm preparations was determined following low- (5 Hz, 1.5 min) and high- (75 Hz, 1 min) frequency stimulation, using glass microelectrodes of the liquid membrane type (pHm). Results were compared with values obtained by the standard homogenate technique (pHh). High- and low-frequency stimulation reduced peak tetanic tension to 21 +/- 1 (SE) and 71 +/- 2% of initial values, respectively. Peak tetanic tension returned to resting values after 10- to 15-min recovery from high- or low-frequency stimulation. Resting pHm was 7.063 +/- 0.011 (n = 72), and after fatiguing stimulation declined to values as low as 6.33. During recovery pHm significantly increased and by 10 min had returned to prefatigue values. No difference was observed in the recovery of pHm between the low- and high-frequency stimulation groups (analysis of variance test, ANOVA), and in both groups pHm recovery was highly correlated to the recovery of peak tetanic tension (r = 0.94, P less than 0.001). Resting pHh was 7.219 +/- 0.023 (n = 13), which was significantly higher than the pHm value. In contrast to pHm, intracellular pHh was significantly higher during recovery from 75- vs. 5-Hz stimulation (P less than 0.05). For both groups pHh increased significantly with time and by 10 min returned to prestimulation values. The ANOVA test demonstrated that pHh values were significantly higher than pHm values during recovery from fatigue. The results from this study support our hypothesis that fatigue from both high- and low-frequency stimulation is at least partially due to the deleterious effects of intracellular acidosis on excitation-contraction coupling.
Effect of cardiogenic gas mixing on arterial O2 and CO2 tensions during breath holding
Authors: Kelly S. M. , Brancatisano A. P. , Engel L. A.
Published: December 2017

To examine the effect of cardiogenic gas mixing on gas exchange we measured arterial tension of O2 (PaO2) and arterial tension of CO2 (PaCO2) during 3- to 5-min breath holds (BH) before and after infusing 50 ml of saline into the pericardial space (PCF) of seven anesthetized, paralyzed, mechanically ventilated dogs. During BH the ventilator was disconnected and a bias flow of 50% O2 at 4–5 l/min was delivered through the side ports of a small catheter whose tip was positioned 1 cm cephalad of the carina. Paired runs, alternately with and without PCF, were performed in triplicate in each dog. Initial PaO2 was similar for control runs [81 +/- 3 mmHg (SE)] and PCF runs (78 +/- 3 mmHg; P greater than 0.1). After 3-min BH, PaO2 in PCF runs (33 +/- 3 mmHg) was less than that in control runs (58 +/- 4 mmHg) (P less than 0.001). In contrast, the pattern of PaCO2 during BH did not differ with PCF. After 3-min BH, PaCO2 was 49 +/- 3 mmHg with PCF and 49 +/- 2 mmHg in the control runs (P greater than 0.7). In two dogs, repeated 50-ml reductions in lung volume, produced by rib cage compression, did not alter the time course of PaO2 during BH. Although cardiac output decreased slightly with PCF, hemodynamic changes due to PCF were unlikely to account for the observed fall in PaO2. Our results indicate a substantial effect of cardiogenic gas mixing on O2 uptake when tracheal gas is O2 enriched during breath holding.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenoreceptor effects on rat muscle blood flow during treadmill exercise
Authors: Laughlin M. H. , Armstrong R. B.
Published: December 2017

The purpose of this study was to examine the effects of the adrenergic receptors on the distribution of blood flow within and among skeletal muscles in rats. Blood flow was measured with the radiolabeled microsphere technique before exercise and during treadmill exercise at 15 or 60 m/min. Alpha- (phentolamine) or beta- (propranolol) adrenergic blocking drugs were administered, and then blood flow was measured and results compared with those from saline-treated rats. Before exercise, alpha-blockade caused increases in total muscle blood flow and in all fast-twitch muscles, whereas muscles composed of greater than 20% slow-twitch fibers showed no effect. During exercise at 15 m/min, the normal increase in total muscle blood flow was attenuated by alpha-blockade. Compared with controls, blood flow was less in the high-oxidative (fast and slow) muscle fiber areas of extensor muscles, whereas blood flow to white areas of extensor muscles was increased. beta-Blockade tended to decrease muscle blood flow before exercise and during exercise at 15 m/min with no apparent relationship between the effects of blockade on blood flow and muscle fiber type. These effects of beta-blockade were not apparent during exercise at 60 m/min. We conclude that before exercise alpha-receptor effects are limited to fast muscle, whereas beta-receptor influences are independent of fiber type, beta-receptors contribute to the initial hyperemia of exercise at 15 m/min, and beta-receptor influence is inversely related to metabolic rate.
Human variation in the peripheral air-space deposition of inhaled particles
Authors: Bennett W. D. , Smaldone G. C.
Published: December 2017

Intersubject variability in both peripheral air-space dimensions and breathing pattern [tidal volume (VT) and respiratory frequency (f)] may play a role in determining intersubject variation in the fractional deposition of inhaled particles that primarily deposit in the lung periphery (i.e., distal to conducting airways). In healthy subjects breathing spontaneously at rest, we measured the deposition fraction (DF) of a 2.6-microns monodisperse aerosol by Tyndallometry while simultaneous measurement of VT and f were made. Under these conditions particle deposition occurs primarily in the peripheral air spaces of the lung. As an index of peripheral air-space size, we used measurements of aerosol recovery (RC) as a function of breath-hold time (t) (Gebhart et al. J. Appl. Physiol. 51: 465–476, 1981). In each subject, we measured RC (aerosol expired/aerosol inspired) of a 1.0-micron monodisperse aerosol as a function of breath-hold time for inspiratory capacity breaths of aerosol. The half time (t1/2) (the breath-hold time to reach 50% RC with no breath hold) is proportional to a mean diameter (D) of air spaces filled with aerosol. In the 10 subjects studied, we found a variable DF, range 0.04–0.44 [0.25 +/- 0.12 (SD)]. DF correlated most closely with 1/f, or the period of breathing (r = 0.96, P less than 0.01). There was no significant correlation between DF and t1/2 as an index of peripheral air-space size. In fact there was little deviation in t1/2 in these normal subjects [coefficient of variation (CV) = 0.12].(ABSTRACT TRUNCATED AT 250 WORDS)
Expiratory activity in transferred intercostal nerves in brachial plexus injury patients
Authors: Sibuya M. , Homma I. , Hara T. , Tsuyama N.
Published: December 2017

Involuntary activity of transferred intercostal motor units was examined in patients with brachial plexus injury. Since the internal intercostal nerves were detached from the thorax to reinnervate the musculus biceps brachii, it was possible to record pure intercostal motor activity in humans. Respiratory activity was seen in the latter part of the expiratory phase, thus dividing the phase into two substages (E1 and E2) by the onset of the activity. CO2 rebreathing prolonged the duration of the intercostal motor activity and increased the tidal activity as determined from the integration curve. There was a close linear correlation between these two variables. These observations indicate that expiratory activity and its duration are actively controlled in humans.
Tissue oxygen extraction during hypovolemia: role of hemoglobin P50
Authors: Schumacker P. T. , Long G. R. , Wood L. D.
Published: December 2017

When the delivery of O2 to tissues (QO2 = blood flow X O2 content) falls below a critical threshold, tissue O2 uptake (VO2) becomes limited by QO2. The mechanism responsible for this extraction limitation is not understood but may involve molecular diffusion limitation as mean capillary PO2 drops below a critical minimum level in some capillaries. We tested this hypothesis by measuring the critical QO2 necessary to maintain VO2 independent of QO2 in anesthetized, paralyzed normal dogs (n = 7) and in a second group in which PO2 at 50% saturation of hemoglobin (P50) was reduced by exchange transfusion with low-P50 erythrocytes (n = 7). QO2 was reduced in stages by removing blood volume to reduce blood flow while VO2 was measured by spirometry at each step. To the extent that O2 extraction was limited by a critical capillary PO2, we reasoned that the onset of diffusion limitation should occur at a higher QO2 with low P50, since a lower end-capillary PO2 is required to achieve the same O2 extraction. The critical QO2 (7.8 +/- 1.2 ml X min-1 X kg-1) and extraction ratio (0.63 +/- 0.06) in dogs with reduced P50 were not different from controls. At the critical delivery, mixed venous PO2 was lower in low P50 (16.1 +/- 2.9 Torr) than controls (29.9 +/- 2.3 Torr). We concluded that diffusion limitation does not initiate the early fall in VO2 below the critical QO2 and offer an alternative model to explain the onset of supply dependency.(ABSTRACT TRUNCATED AT 250 WORDS)
Relations among alveolar surface tension, surface area, volume, and recoil pressure
Authors: Bachofen H. , Schurch S. , Urbinelli M. , Weibel E. R.
Published: December 2017

For pulmonary structure-function analysis excised rabbit lungs were fixed by vascular perfusion at six points on the pressure-volume (P-V) curve, i.e. at 40, 80, and 100% of total lung capacity (TLC) on inflation, at 80 and 40% TLC on deflation, and at 80% TLC on reinflation. Before fixation alveolar surface tensions (gamma) were measured in individual alveoli over the entire P-V loop, using an improved microdroplet method. A maximal gamma of approximately 30 mN/m was measured at TLC, which decreased during lung deflation to about 1 mN/m at 40% TLC. Surface tensions were considerably higher on the inflation limb starting from zero pressure than on the deflation limb (gamma-V hysteresis). In contrast, the corresponding alveolar surface area-volume (SA-V) relationship did not form a complete hysteresis over the entire volume range. There was a considerable difference in SA between lungs inflated to 40% TLC (1.49 +/- 0.11 m2) and lungs deflated to 40% TLC (2.19 +/- 0.21 m2), but at 80% TLC the values of SA were essentially the same regardless of the volume history. The data indicate that the gamma-SA hysteresis is only in part accountable for the P-V hysteresis and that the determinative factors of alveolar geometry change with lung volume. At low lung volumes airspace dimensions appear to be governed by an interplay between surface and tissue forces. At higher lung volumes the tissue forces become predominant.
Vascular pressure effects on lung edema formation after glass bead embolism
Authors: Ehrhart I. C. , Hall J. E. , Hofman W. F.
Published: December 2017

The canine lung lobe was embolized with 100-micron glass beads before lobectomy and blood anticoagulation. The lobe was isolated, ventilated, and pump-perfused with blood at an arterial pressure (Pa) of about 50 (high pressure, HP, n = 9) or 25 Torr (low pressure, LP, n = 9). Rus/PVR, the ratio of upstream (Rus) to total lobar vascular resistance (PVR), was determined by venous occlusion and the isogravimetric capillary pressure technique. The capillary filtration coefficient (Kf), an index of vascular permeability, was obtained from rate of lobe weight gain during stepwise capillary pressure (Pc) elevation. The embolized lobes became more edematous than nonembolized controls, (C, n = 11), (P less than 0.05), with Kf values of 0.20 +/- 0.04, 0.25 +/- 0.06, and 0.07 +/- 0.01 ml X min-1 X Torr-1 X 100 X g-1 in LP, HP, and C, respectively (P less than 0.05). The greater Rus/PVR in embolized lobes (P less than 0.05) protected the microvessels and, although Pc was greater in HP than in controls (P less than 0.05), Pc did not differ between HP and LP (P greater than 0.05). Although indexes of permeability did not differ between embolized groups (P greater than 0.05), HP became more edematous than LP (P less than 0.05). The greater edema in HP did not appear due to a greater imbalance of Starling forces across the microvessel wall or to vascular recruitment. At constant Pc and venous pressure, elevating Pa from 25 to 50 Torr in embolized lobes resulted in greater edema to suggest fluid filtration from precapillary vessels.
Inhibition of aortic chemoreceptor discharge by pressor response to muscular contraction
Authors: McCoy K. W. , Rotto D. M. , Kaufman M. P.
Published: December 2017

We have examined the effect of static contraction of the hindlimb muscles on the discharge of aortic chemoreceptors in chloralose-anesthetized cats. The responses of the chemoreceptors to contraction were dependent on the arterial pressure response to this maneuver. When contraction reflexly evoked a pressor response of at least 20 mmHg, the discharge of 26 chemoreceptors was reduced from control levels by 53% (P less than 0.01). The contraction-induced inhibition of chemoreceptor discharge was prevented by phentolamine, an alpha-adrenergic antagonist that also attenuated the contraction-induced pressor response. In addition, the inhibition evoked by contraction was simulated by injection of phenylephrine and inflation of an aortic balloon, both of which evoked pressor responses. However, when contraction failed to significantly change arterial pressure, the discharge of 20 aortic chemoreceptors was not significantly changed from control levels. We conclude that the reflex pressor response to static contraction inhibits the discharge of aortic chemoreceptors. This inhibition of discharge needs to be considered when interpreting the effects of aortic barodenervation on the cardiovascular responses to exercise.
Systemic arterial blood supply to the trachea and lung in sheep
Authors: Charan N. B. , Turk G. M. , Czartolomny J. , Andreazuk T.
Published: December 2017

We studied the systemic arterial blood supply to the trachea and lung in adult sheep. After anesthesia, sheep were exsanguinated and then studied by intra-arterial injection of one of the following materials: saline containing dyes of various colors (n = 24), Microfil (n = 8), or Batson's solution (n = 6). The systemic blood supply to the cervical trachea originated from the two common carotid arteries via three to four small branches (rami tracheales cervicales) on each side. A segment of the thoracic trachea between the thoracic inlet and the origin of the tracheal bronchus (bronchus trachealis) and the bronchial tree of the right cranial lobe (lobus cranialis dexter) were supplied by the tracheal bronchial branch (ramus bronchalis trachealis), which originated from the brachiocephalic trunk (truncus brachiocephalicus). A portion of thoracic trachea between the origin of the tracheal bronchus and the tracheal carina was supplied by the thoracic tracheal branch (ramus trachealis thoracica), arising from the bronchoesophageal artery (arteria bronchoesophagea) or directly from the thoracic aorta. The bronchial branch (ramus bronchalis) originated from the bronchoesophageal artery, and its branches supplied the remainder of the bronchial tree. At 120 cmH2O pressure (n = 8), the bronchial branch contributed approximately 50% and the other two approximately 25% each of the total tracheobronchial blood flow. These three branches also supplied the visceral pleura. Additionally, several small vessels (rami pleurales pulmonales) originated from the esophageal branch (ramus esophagea) of the bronchoesophageal artery, traversed the pulmonary ligaments, and supplied the visceral pleura.
Groucho running
Authors: McMahon T. A. , Valiant G. , Frederick E. C.
Published: December 2017

An important determinant of the mechanics of running is the effective vertical stiffness of the body. This stiffness increases with running speed. At any one speed, the stiffness may be reduced in a controlled fashion by running with the knees bent more than usual. In a series of experiments, subjects ran in both normal and flexed postures on a treadmill. In other experiments, they ran down a runway and over a force platform. Results show that running with the knees bent reduces the effective vertical stiffness and diminishes the transmission of mechanical shock from the foot to the skull but requires an increase of as much as 50% in the rate of O2 consumption. A new dimensionless parameter (u omega 0/g) is introduced to distinguish between hard and soft running modes. Here, omega 0 is the natural frequency of a mass-spring system representing the body, g is gravity, and u is the vertical landing velocity. In normal running, this parameter is near unity, but in deep-flexed running, where the aerial phase of the stride cycle almost disappears, u omega 0/g approaches zero.
Forced expiratory wheezes are a manifestation of airway flow limitation
Authors: Gavriely N. , Kelly K. B. , Grotberg J. B. , Loring S. H.
Published: December 2017

To study the mechanism of generation of respiratory wheezes we examined the relationships between forced expiratory wheezes (FEW) and flow limitation in the lung. Tracheal lung sounds were measured in six healthy subjects during forced expiration through a flow-limiting valve in series with a high-impedance suction pump. Mouth pressure, esophageal pressure, transpulmonary pressure (Ptp), flow (V), and volume were also measured. For any flow rate, V was constant until the subject became flow limited. The onset of flow limitation was documented by a small change in V and a sudden change in Ptp, which was previously found by Olafsson and Hyatt to correspond to the beginning of the flow plateau of the isovolume pressure-flow curve (J. Clin. Invest. 48: 564–573, 1969). FEW started 107 +/- 45 ml (SD) after the onset of flow limitation. Additional 79 +/- 65 ml were exhaled between the onset of FEW to the final sharp drop in V. The frequency spectra of FEW were the same as those of respiratory wheezes found in obstructive airway diseases. Administration of inhaled bronchodilator (isoproterenol) did not eliminate the FEW, nor did it change their relationship to flow limitation. The sequence of events around the onset of FEW, and the tight correlation with the onset of flow limitation correspond well to recent experimental observations on the onset of flutter in collapsible, thick-walled latex tubes.
Effects of crystalloid and colloid fluids on extravascular lung water in hypoproteinemic dogs
Authors: Rackow E. C. , Weil M. H. , Macneil A. R. , Makabali C. G. , Michaels S.
Published: December 2017

We compared the effect of crystalloid to colloid fluid infusion on extravascular lung water (EVLW) in hypoproteinemic dogs. Plasmapheresis was used to decrease plasma colloid osmotic pressure (COP) to less than 40% of its base-line level. Five animals were then infused with 0.9% sodium chloride (saline), five with 5% human serum albumin (albumin), and five with 6% hydroxyethyl starch (hetastarch) to increase the pulmonary arterial occlusive pressure by 10 Torr in comparison to the postplasmapheresis level for a 5-h study interval. On completion of the procedure, the lungs were harvested and EVLW measured by the blood-free gravimetric technique. Three to six times the volume of saline compared with albumin or hetastarch (P less than 0.001) was infused. In the saline animals, COP was decreased to 3.3 +/- 1.3 Torr, whereas COP was increased to 18.1 +/- 1.4 Torr in albumin animals (P less than 0.001) and 20.1 +/- 1.6 Torr in the hetastarch group (P less than 0.001). The saline-treated dogs developed gross signs of systemic edema. The EVLW was 8.1 +/- 0.9 ml/kg in saline animals compared with 5.3 +/- 2.1 ml/kg in the albumin (P less than 0.05) and 4.1 +/- 1.4 ml/kg in the hetastarch (P less than 0.01) groups. These data indicate that crystalloid fluid infusion during hypoproteinemia is associated with the development of both systemic and pulmonary edema.
Diaphragm afferent modulation of phrenic motor drive
Authors: Fryman D. L. , Frazier D. T.
Published: December 2017

Experiments were performed in eight lightly anesthetized thiopental sodium (Pentothal) cats to examine whether diaphragmatic afferents can significantly alter the neural drive to the diaphragm when the animal is exposed to lower body negative pressure. Moving-time-averaged diaphragmatic electromyograms (EMGma) were recorded and compared before and during exposure to lower body negative pressure in each of three consecutive conditions: C7 spinalization, bilateral vagotomy, and cervical dorsal rhizotomy. Application of lower body negative pressure in C7-spinalized animals resulted in a decrease in inspiratory time and peak diaphragmatic activity compared with control levels. After bilateral vagotomy, EMGma activity was prolonged with the application of lower body negative pressure. However, there was no increase in peak EMGma activity. After transection of the cervical dorsal roots subserving the phrenic nerve, the prolongation of diaphragmatic activity negative was eliminated. Therefore, we conclude that the significant increase in duration of inspiration in response to application of lower body negative pressure in the C7-spinalized, bilaterally vagotomized cat is mediated by phrenic nerve afferents.
Ventilatory control in hypercapnia and exercise: optimization hypothesis
Authors: Poon C. S.
Published: December 2017

A model of the respiratory control system incorporating both chemical and respiratory neuromechanical feedbacks is proposed to describe the steady-state ventilatory responses to CO2 inhalation and exercise. It is postulated that ventilatory output (VE) is set by the respiratory center to minimize a net operating cost representing the conflicting challenges of arterial chemical imbalance and respiratory-mechanical discomfort (intolerance of effort), given, respectively, by a quadratic function of arterial PCO2 and a logarithmic function of VE. In addition, the system is assumed to be mechanically limited at maximum VE (Vmax). The predicted responses in VE during moderate hypercapnia, exercise, and ventilatory loading closely mimic those normally observed, even though no separate signal unique to exercise is assumed. As a quantitative validation, the model yielded good fits to ventilatory response data obtained in eight healthy subjects during eucapnic and hypercapnic exercise; the predicted Vmax averaged approximately 77% of the maximum voluntary ventilation in all subjects. The results demonstrate the plausibility of the proposed optimization mechanism and suggest an important role for respiratory-mechanical factors in the control of VE.
Hypoxia-induced changes in shivering and body temperature
Authors: Gautier H. , Bonora M. , Schultz S. A. , Remmers J. E.
Published: December 2017

Experiments were carried out on conscious cats to evaluate the general characteristics and modes of action of hypoxia on thermoregulation during cold stress. Intact and carotid-denervated (CD) conscious cats were exposed to ambient hypoxia (low inspired O2 fraction) or CO hypoxia in prevailing laboratory (23–25 degrees C) or cold (5–8 degrees C) environments. In the cold, both groups promptly decreased shivering and body temperature when exposed to either type of hypoxia. Small increases in CO2 concentration reinstituted shivering in both groups. At the same inspired concentration of O2, CD animals decreased shivering and body temperature more than intact cats. While this difference resulted, in part, from a lower alveolar PO2 in CD cats, a difference between intact and CD cats was apparent when the two groups were compared at the same alveolar PO2. During more prolonged hypoxia (45 min), shivering returned but did not reach normoxic levels, and body temperature tended to stabilize at a hypothermic value. Exposure to various levels of hypoxia produced graded suppression of shivering, with the result that the change in body temperature varied directly with inspired O2 concentration. Hypoxia appears to act on the central nervous system to suppress shivering and sinus nerve afferents appear to counteract this direct effect of hypoxia. In intact cats, this counteraction appears to be sufficient to maintain body temperature under hypoxic conditions at room temperature but not in the cold.