bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of route of atropine delivery on bronchospasm from cold air and methacholine
Authors: Sheppard D. , Epstein J. , Holtzman M. J. , Nadel J. A. , Boushey H. A.
Published: December 2017

We undertook a study to determine whether the apparent disparity between the dose of inhaled atropine required to inhibit the bronchoconstriction induced by inhaled methacholine and the dose required to inhibit the bronchoconstriction induced by eucapnic hyperpnea with cold air is a function of the route of administration of atropine. In six subjects with asthma, we constructed dose-response curves to inhaled methacholine and to eucapnic hyperpnea with cold air after treatment with inhaled atropine (0.5 mg delivered) and intravenous placebo, with inhaled placebo and intravenous atropine (0.5 mg injected), and with inhaled and intravenous placebos. Atropine by either route shifted the dose-response curves to both cold air and to methacholine to the right. In every subject, however, inhaled atropine caused a markedly greater rightward shift of the inhaled methacholine dose-response curve than did intravenous atropine, whereas inhaled and intravenous atropine had similar effects on the cold air dose-response curve. These findings suggest that the apparent disparity between the doses of atropine required to inhibit methacholine- and cold air-induced bronchoconstriction may be a function of the route of administration of atropine and thus does not imply a nonmuscarinic action of atropine. The findings support the view that cold air causes bronchoconstriction via muscarinic pathways.
Effects of transient intracranial hypertension on lung fluid and protein exchange
Authors: van der Zee H. , Neumann P. H. , Minnear F. L. , Malik A. B.
Published: December 2017

We determined whether a transient increase in intracranial pressure (Pic) increases lung vascular permeability and whether the increase occurs at a Pic threshold. Anesthetized sheep were prepared with lung lymph fistulas. Pic was increased by rapidly injecting 20–45 ml of freshly drawn autologous blood into the cisterna magna from a base line of 4.8 +/- 1.5 Torr to a peak mean value of either 142.0 +/- 17.6 Torr (group I, n = 5) or 70.3 +/- 3.5 Torr (group II, n = 5). Pic decreased to 34.6 +/- 2.2 Torr in group I and to 31.0 +/- 3.2 Torr in group II within 1 h and remained steady at these levels for the study. The Cushing response (i.e., marked systemic hypertension lasting 10–15 min) was elicited only in group I; changes in mean pulmonary arterial (Ppa) and mean pulmonary arterial wedge (Ppw) pressures during the first 15 min were small, pulmonary blood flow (QL) increased, and pulmonary vascular resistance (PVR) decreased only in the first 15 min after the intracisternal injection. In group II, Ppa and QL did not change significantly, but PVR increased after the increase in Pic. Both pulmonary lymph flow (Qlym) and transvascular protein clearance (CL) increased only in sheep with the Cushing response. In group III (n = 8) in which Qlym and CL increased after intracranial hypertension as in group I, the left atrial pressure was raised to increase the pulmonary capillary pressure (Pc) to determine the basis for the increases in Qlym and CL (i.e., whether vascular surface area or permeability increased). The increase in Pc produced a small increase and decrease in lymph-to-plasma protein concentration ratio, indicating that the transient increase in Pic did not increase endothelial permeability to proteins. The increases in Qlym and CL were due to increased pulmonary vascular surface area.
Simultaneous comparison of tracheobronchial and right duct lymph dynamics in dogs
Authors: Martin D. J. , Parker J. C. , Taylor A. E.
Published: December 2017

The simultaneous responses of lymph flow and protein concentration were compared using lymph from the right duct (RD) and small afferent tracheobronchial (TB) lymphatics cannulated in the same dog. Lymph was collected during a base-line period and following steady-state left atrial pressure (Pla) elevations. For a mean increase in Pla of 14.8 cmH2O, RD flow increased 1.1 times control and TB flow by 2.5 times control. Total protein lymph-to-plasma ratios decreased significantly for TB lymph but not for RD lymph. Assuming TB represented pure lung lymph, the right duct was estimated to drain 4% of the total lung lymph and consist of 11% lung lymph with 89% extrapulmonary lymph at normal lymph flows. The lung lymph contribution to RD flow increased to 24% with increased Pla. Equivalent capillary pore dimensions calculated using endogenous protein fractions in both RD and TB lymph resulted in small pores of 100 and 90 A and large pores of 220 and 225 A, respectively. The fraction filtered through the large-pore population estimated using RD lymph was half that predicted using TB lymph. These data indicate that RD lymph data cannot accurately reflect pulmonary vascular permeability, since extrapulmonary lymph provided a major component of RD lymph flow at both base-line and increased filtration states.
Physiological and pharmacological response of canine bronchial smooth muscle in situ
Authors: Hendrix S. G. , Munoz N. M. , Leff A. R.
Published: December 2017

We studied the isometric response of bronchial smooth muscle in a single third-order bronchus of 24 dogs in situ. Length-tension studies were performed in six dogs by repeated injection of 10(-5) mol acetylcholine (ACh) into the right bronchoesophageal artery, and the resting tension (30.6 +/- 6.9 g/cm) and length (0.76 +/- 0.14 cm) permitting maximal contraction were determined. In eight other dogs, dose-related bronchial contraction was obtained with 10(-10) to 10(-5) mol intra-arterial (ia) ACh. Supramaximal electrical stimulation of the right cervical vagus nerve and bronchial parasympathetic ganglion stimulation with ia 1–1-dimethyl-4-phenylpiperazinium (DMPP) also caused bronchial contraction. The maximal response to ia ACh (28.5 +/- 1.7 g/cm), supramaximal electrical stimulation (15.2 +/- 1.1 g/cm), and ia DMPP (10.5 +/- 3.0 g/cm) was blocked by an ia dose of atropine (1–5 micrograms/kg) that did not alter the sympathetic relaxation response in the trachea. In four dogs, the bronchial response to sympathetic activation was studied by intravenous (iv) bolus injection of DMPP after cholinergic blockade with atropine. DMPP (25 micrograms/kg iv) caused 9.5 +/- 2.2 g/cm bronchial relaxation, which was blocked completely by 2–4 mg/kg iv propranolol. In six other dogs, hypoxia induced by ventilation with pure nitrogen caused bronchial contraction, which was blocked by vagotomy, atropine, and hexamethonium. We report a sensitive method for selective measurement of bronchial smooth muscle response in a single resistance bronchus. This preparation preserves regional innervation and circulation and permits selective physiological stimulation in situ.
An elastic loading system for ventilatory studies in small animals
Authors: LaFramboise W. A. , Tuck R. E. , Standaert T. A. , Woodrum D. E.
Published: December 2017

A system for studying the effects of prolonged inspiratory elastic loading in small animals (300–500 g) is described. A voltage comparator triggered by the expired flow signal activates a solenoid valve to vent the loading chamber after each inspiratory decompression, ensuring the presentation of a constant extrapulmonary elastance. The sensitivity of the comparator (5 mV) and the response time of the venting circuit (40 ms) make this system suitable for use in small subjects with tidal volumes less than 1 ml and respiratory frequencies exceeding 100 breaths . min-1. Additionally, the composition of the inspiratory gas is easily altered and a built-in device allows end-expiratory occlusions to be performed.
Errors in calculating cardiac output due to administration of perfluorochemicals
Authors: Rosen A. L. , Gould S. A. , Sehgal L. R. , Sehgal H. L. , Moss G. S.
Published: December 2017

Intravenous administration of perfluorochemicals (PFC) will alter the density (rho)B, the gravimetric specific heat (c)B, and the volumetric specific heat (rho c)B of blood. Changes in hematocrit also influence (rho c)B. The calibration constant employed in the determination of cardiac output (CO) by thermal dilution depends inversely on (rho c)B. We estimate the effect of addition of PFC and changes in hematocrit on (rho c)B. Consider blood to be a mixture of red cells, emulsified PFC particles, and plasma. This leads to the equation: (rho c)cB = 0.96 - 0.11Hct - 0.48Fct. Here Hct and Fct are the fractional volume concentrations of red blood cells and PFC, and (rho c)cB is the calculated specific heat based on the actual composition of blood. CO can be corrected for changes in (rho c)B by the equation: (CO)c = [(rho c)sB/(rho c)cB](CO)o. Here (CO)o is the observed cardiac output, (rho c)sB is the standard specific heat of blood used in the calculation of (CO)o, and (CO)c is the corrected cardiac output. We have observed laboratory situations where the correction factors have been as high as 10%.
Eccentric exercise-induced injury to rat skeletal muscle
Authors: Armstrong R. B. , Ogilvie R. W. , Schwane J. A.
Published: December 2017

These experiments were designed to study skeletal muscle pathology resulting from eccentric-biased exercise in rats. The effects on the muscles of running on a treadmill on a 0 degrees incline (similar amounts of concentric and eccentric contractions), down a 16 degrees incline (primarily eccentric contractions), and up a 16 degrees incline (primarily concentric contractions) at 16 m . min-1 for 90 min were assessed by following postexercise changes in 1) plasma creatine kinase and lactate dehydrogenase activities, 2) glucose-6-phosphate dehydrogenase (G-6-PDase) activity (bio- and histochemically) in the physiological extensor muscles, and 3) histological appearance of the muscles. The data indicate the following. 1) Whereas all exercise protocols resulted in elevations of plasma enzymes immediately after running, only eccentric exercise caused late phase elevations 1.5–2 days postexercise. 2) Significant increases in muscle G-6-PDase activity, which were always associated with accumulations of mononuclear cells, always occurred within some muscles of each extensor group 1–3 days following downhill and uphill running and did not occur following level running; the increases in activity were usually of lower magnitude in the muscles of uphill runners than in those of downhill runners; the deeply located, predominantly slow-twitch muscles were most affected by both down- and uphill running. 3) Muscle histology demonstrated localized disruption of normal banding patterns of some fibers immediately after exercise and accumulations of macrophages in the interstitium and in some (less than 5%) muscle fibers by 24 h postexercise in the deep slow muscles of the antigravity groups. Although the data generally indicated that eccentric exercise causes greater injury to the muscles, questions remain.
Respiratory heat and water exchange: physiological and clinical implications
Authors: McFadden E. R.
Published: December 2017

Recent evidence demonstrates that the conditioning of inspired air is not confined to the upper airways as formerly thought but rather involves as much of the tracheobronchial tree as necessary to complete the process. As the need to condition more air is increased by raising ventilation and/or lowering inspired temperature (and so water content), the point at which the inspirate reaches body conditions moves progressively deeper into the lungs, and under extreme conditions thermal transfers can be measured in airways less than 2 mm in diameter. The decrease in airway temperature that develops from the movement of heat and water from the mucosa during inspiration not only facilitates recovery during expiration by reversing the thermal gradients, but it may also produce airway obstruction in susceptible individuals by an as yet undefined mechanism. Respiratory heat exchange may also interact with airway secretory processes and mucociliary transport mechanisms and may help regulate bronchial blood supply.
Human frontal sweat rate and lactate concentration during heat exposure and exercise
Authors: Fellmann N. , Grizard G. , Coudert J.
Published: December 2017

Output (Qsweat) and lactate concentration ( [L]sweat) in frontal sweat and blood lactate concentration ( [L]blood) were monitored in three male volunteers: one sedentary (S), one fit (F), and one very fit (VF). Measurements were made under three sweating conditions: 1) heat exposure to infrared radiation (IR) at rest for 25 min at 45 degrees C; 2) bicycle exercise at constant relative maximal aerobic power (87 +/- 2% MAP) for 25 min (Cst EX) at 23 degrees C; and 3) bicycle exercise at increasing work loads (from 60–95% MAP) in four or five successive 5-min steps (Incr EX) at 23 degrees C. Comparison of these data showed that under the above three conditions 1) Qsweat of S was lower than that of F and VF; and 2) changes in [L]sweat were different: in IR and Cst EX, [L]blood remained constant, and [L]sweat decreased with heat load duration similarly in the three subjects (the slopes of the two curves were not significantly different); at Incr Ex, [L]blood increased and [L]sweat remained constant in S, F, and VF (21.71 +/- 0.85, 16.75 +/- 0.99, 12.83 +/- 0.45 (SE) mM, respectively). It was suggested that the high [L]blood and increased adrenergic stimulation observed in Incr Ex could act on [L]sweat in relation to the physical fitness level.
Regional gas distributions and single-breath washout curves in head-down position
Authors: Demedts M. , Clarysse I. , Verhamme M. , Marcq M. , De Roo M.
Published: December 2017

Regional distributions of inspired 133Xe and single-breath washout curves were compared in six young healthy subjects for the upright and the head-down positions. The regional distributions of volumes (at 0, 25, 50, and 75% vital capacity, VC) and of 133Xe boluses inhaled at residual volume (RV) were inverted in the head-down position, thus behaving as if they were determined by gravity acting via the weight of the lung rather than by thoracicoabdominal shape adaptations. Nevertheless no mirror image was obtained. The vertical differences in regional distribution of the 133Xe RV bolus and of the volumes at 25% VC were increased in the head-down position, whereas the vertical difference in volumes at RV was decreased, indicating enhanced air trapping and sequential ventilation at low volumes. This was attributed to the effect of the increased pulmonary blood volume in the head-down posture. Accordingly the size of phase IV on the washout curves with the SF6-bolus as well as with the N2-resident gas method was increased in the head-down position.
Increased cardiovascular response to static contraction of larger muscle groups
Authors: Seals D. R. , Washburn R. A. , Hanson P. G. , Painter P. L. , Nagle F. J.
Published: December 2017

The purpose of this study was to investigate the influence of the size of the active muscle mass on the cardiovascular response to static contraction. Twelve male subjects performed one-arm handgrip (HG), two-leg extension (LE), and a “dead-lift” maneuver (DL) in a randomly assigned order for 3 min at 30% of maximal voluntary contraction. O2 uptake (VO2), heart rate (HR), and mean intra-arterial blood pressure (MABP) were measured at rest and, in addition to absolute tension exerted, throughout contraction. There was a direct relationship between the size of the active muscle mass and the magnitude of the increases in VO2, HR, and MABP, even though all contractions were performed at the same relative intensity. Tension, VO2, HR, and MABP increased progressively from HG to LE to DL. It was concluded that at the same percentage of maximal voluntary contraction, the magnitude of the cardiovascular response to isometric exercise is directly influenced by the size of the contracting muscle mass.
Respiratory muscle function during CO2 rebreathing with inspiratory flow-resistive loading
Authors: Lopata M. , Onal E. , Ginzburg A. S.
Published: December 2017

We investigated the respiratory muscle contribution to inspiratory load compensation by measuring diaphragmatic and intercostal electromyograms (EMGdi and EMGic), transdiaphragmatic pressure (Pdi), and thoracoabdominal motion during CO2 rebreathing with and without 15 cmH2O X l-1 X s inspiratory flow resistance (IRL) in normal sitting volunteers. During IRL compared with control, Pdi measured during airflow and during airway occlusion increased for a given change in CO2 partial pressure and EMGdi, and there was a greater decrease in abdominal (AB) end expiratory anteroposterior dimensions with increased expiratory gastric pressure (Pga), this leading to an inspiratory decline in Pga with outward AB movement, indicating a passive component to the descent of the abdomen-diaphragm. The response of EMGic to IRL was similar to that of EMGdi, though rib cage (RC)-Pga plots did infer intercostal muscle contribution. We conclude that during CO2 rebreathing with IRL there is improved diaphragmatic neuromuscular coupling, the prolongation of inspiration promoting a force-velocity advantage, and increased AB action serving to optimize diaphragm length and configuration, as well as to provide its own passive inspiratory action. Intercostal action provides increased assistance also. Therefore, compensation for inspiratory resistive loads results from the combined and integrated effort of all respiratory muscle groups.
Effects of repetitive exercise on neonatal rat skeletal muscle oxidative capacity
Authors: MacIntosh A. M. , Baldwin K. M.
Published: December 2017

Since little is known about the training response to exercise in neonatal animals, this study was undertaken to elucidate the potential of oxidative system adaptations in developing skeletal muscle of rats during 50 days of daily treadmill running. The training regimen involved male and female rats (10 days old) initially running 0.1 mph, 0% grade, for 15 min. The program progressed to 1 mph, 25% grade, for 60 min by 50 days of age. At 25 days of age, pyruvate and palmitate oxidative capacity, and citrate synthase activity in red vastus muscle homogenates were elevated in the trained group (T) compared with age- and sex-matched controls (C). These increases were also observed for each subsequent time point tested and occurred in spite of the fact that the peak oxidative capacity of neonatal red vastus muscle was 46% greater than adult values. Further, trained animals tested at 45 days of age responded with a 12% increase in maximal oxygen consumption (Vo2max) compared with controls (P less than 0.05). Assays of muscle phosphofructokinase and of creatine phosphokinase activity conducted at this time point revealed no difference between T and C groups. Collectively, these data suggest that neonatal rats can be successfully trained and that they respond to an endurance-type program qualitatively similarly to adult rats.
Responses of the lung periphery to ozone and histamine
Authors: Gertner A. , Bromberger-Barnea B. , Traystman R. , Berzon D. , Menkes H.
Published: December 2017

We studied the effects of ozone (O3) and histamine on the lung periphery. A fiber-optic bronchoscope was wedged in a segmental airway of anesthetized male mongrel dogs. Measurements of collateral resistance (Rcoll) were used to monitor responses to O3 and to histamine. Both agents were delivered locally through the bronchoscope. During a 30-min exposure to 0.1 ppm O3, Rcoll increased 31.5 +/- 5.1% within 2 min and then gradually decreased toward control levels in spite of continued exposure to O3. Within 15 min after the exposure ceased, Rcoll had returned to base line. Subsequent exposure to 0.1 ppm O3 did not increase Rcoll. During a 30-min exposure to 1.5 X 10(-6) mg/min histamine aerosol, Rcoll increased 21.5 +/- 5.0% within 2 min and persisted at an elevated level throughout the exposure. Subsequent exposures to histamine produced similar increases in Rcoll. Bilateral cervical vagotomy or pretreatment with atropine aerosol (0.1 mg) prevented responses to O3 but did not prevent responses to histamine. These results indicate that responses to O3, unlike responses to histamine in the lung periphery, are characterized by the rapid development of adaptation and tolerance and are mediated through the vagus nerves.
Inhibition of breathing movements in fetal sheep by prostaglandins
Authors: Kitterman J. A. , Liggins G. C. , Fewell J. E. , Tooley W. H.
Published: December 2017

We studied the effects of infusions (duration 13.4 +/- 2.9 h) of prostaglandins (PG) on fetal breathing movements (FBM) in 12 fetal sheep at 122–141 days gestation. We gave similar doses (1.1 +/- 0.7 microgram . kg-1 . min-1) of PGE2 (8 studies), PGF2 alpha (5 studies), and cyclic endoperoxide analogues (6 studies). During control periods (304 h), incidence of FBM was 41%; this decreased during every infusion. With PGE2, incidence of FBM markedly decreased to 9.8% of control (P less than 0.001). With the other agents the decrease was less profound; incidence of FBM with PGF2 alpha was 63.7% of control and with endoperoxide analogues 69.4% of control (P less than 0.05 for both). During infusions there were no changes in fetal heart rate, arterial blood pressure, pH, or blood gas tensions. In three fetuses (5 infusions) with electrocorticogram recordings, incidence of low-voltage fast activity was unchanged from control values. Inhibition of FBM by PGE2, combined with previous results showing stimulation of FBM by PG synthetase inhibitors, suggests that endogenous PG may inhibit breathing movements in utero and that a change in PG metabolism may contribute to the change in control of breathing at birth.
Effects of acute hypercapnia on the central and peripheral circulation of conscious sheep
Authors: Matalon S. , Nesarajah M. S. , Krasney J. A. , Farhi L. E.
Published: December 2017

We studied the cardiorespiratory effects of acute hypercapnia in 10 unanesthetized sheep. After a 15-min exposure to either 7.3 or 10% CO2 in air, we measured arterial blood gases, minute ventilation (VE), O2 consumption (VO2), cardiac output (Q), heart rate (HR), an index of left ventricular contractility [(dP/dt)/P], and vascular pressures. In addition, regional flows to all major organs were determined by injecting 15-microns radiolabeled microspheres into the left heart. Exposure to 7.3% CO2 (arterial CO2 partial pressure, PaCO2, 58 Torr) resulted in increased VE, (dP/dt)/P, and higher blood flows to the brain and respiratory muscles. All other variables remained unchanged. Exposure to 10% CO2 (PaCO2 75 Torr) resulted in a further augmentation of VE and a 48% increase in Q, which was associated with a tachycardia, a decrease in systemic vascular resistance, and an increase in VO2. Coronary and respiratory muscle flows increased, but all other variables remained unchanged. Thus the hemodynamic effects of hypercapnia are not related linearly to the level of PaCO2.
Alveolar size as a determinant of pulmonary distensibility in mammalian lungs
Authors: Haber P. S. , Colebatch H. J. , Ng C. K. , Greaves I. A.
Published: December 2017

Pulmonary distensibility depends on surface tension and tissue elastic forces, but the relative contribution of each to total lung recoil remains incompletely defined. By applying an exponential analysis to static pressure-volume curves obtained from the excised lungs of cats, dogs, and rats with air and saline filling, the exponential constant K (an index of lung distensibility) was related to the mean linear intercept Lm (a morphometric estimate of the mean size of peripheral air spaces at maximal inflation). K for air filling (Ka) was unrelated to K for saline filling (Ks), and Ks was unrelated to Lm, but similar highly significant regressions of Ka on Lm were found in each species, and the common regression was similar to that described previously for human lungs. Approximately 86% of the variance in lung distensibility (Ka) within and between species was explained by Lm. Because Lm determines the size of air spaces, and therefore the alveolar surface-to-volume ratio, the findings indicate that the density of surface forces is the major determinant of lung distensibility in the air-filled state.
Changes in diastolic coronary resistance during submaximal exercise in conditioned dogs
Authors: Liang I. Y. , Stone H. L.
Published: December 2017

Diastolic coronary resistance (DCR) was studied in 10 conscious dogs in the untrained (UT) and partially trained (PT) condition. The PT regime consisted of treadmill running 5 days/wk for 4–5 wk. Left circumflex coronary flow, aortic pressure, and heart rate were measured, and diastolic coronary resistance (DCR) was calculated. Adrenergic blockade was achieved with propranolol (1 mg/kg, iv) (beta B) and phentolamine (1 mg/kg, iv) (alpha B). During submaximal exercise in the UT condition, DCR fell from a resting value of 3.84 +/- 0.24 Torr . ml-1 . min with increasing work load to 1.57 +/- 0.12 Torr . ml-1 . min at 6.4 km/h (speed)/16% (grade). The decrease in DCR during submaximal exercise was greater in the PT than in the UT condition. DCR following alpha-adrenergic blockade was not significantly changed in the UT and PT conditions (e.g., at 6.4 km/h (speed)/16% (grade), 1.10 +/- 0.141 vs. 1.03 +/- 0.107 Torr . ml-1 . min, whereas following beta-adrenergic blockade, DCR was larger in the UT compared with the PT condition (e.g., at 6.4 km/h (speed)/16% (grade), 2.03 +/- 0.091 vs. 1.73 +/- 0.073 Torr . ml-1 X min). Myocardial oxygen consumption was not significantly different in the PT and UT conditions, indicating no difference in metabolism with partial training. The present study suggests that during submaximal exercise in the PT condition there is a change in the neurogenic control of the coronary vasculature by a reduction in sympathetic neural activity on the coronary resistance vessels.
Effects of low concentrations of chlorine on pulmonary function in humans
Authors: Rotman H. H. , Fliegelman M. J. , Moore T. , Smith R. G. , Anglen D. M. , Kowalski C. J. , Weg J. G.
Published: December 2017

Eight healthy unacclimated volunteers were exposed to chlorine gas in concentrations of 0.5 or 1 ppm, and several pulmonary function measurements were made. Comparisons were made by paired t test between the percent change from base-line values obtained at various times after chlorine exposure and the percent change from base line at analogous times after a sham exposure. With the sham vs. 0.5-ppm exposure, there were trivial changes observed. Total lung capacity (TLC) was lower before 0.5-ppm exposure than before sham exposure, and the percent decrease in carbon dioxide pulmonary diffusing capacity was smaller 24 h after 0.5-ppm exposure than 24 h after sham exposure. With the sham vs. 1-ppm exposure, there were many differences in percent change from base line that were significant at the P less than 0.05 level or better. These were in forced vital capacity (FVC), forced expiratory volume at 1 s (FEV1), peak expiratory flow rate (PEFR), forced expiratory flow rate at 50 and 25% vital capacity (FEF50 and FEF25, respectively), and airway resistance (Raw). There were, in addition, significant changes after only 4 h of exposure. These were in FEV1, PEFR, FEF50, FEF25, TLC, Raw, and the difference in nitrogen concentration. Most of the test results had returned to normal by the next day. We conclude that even though chlorine at low concentrations does not produce any serious subjective symptoms, it adversely affects pulmonary function transiently.
Liquid ventilation in dogs: an apparatus for normobaric and hyperbaric studies
Authors: Harris D. J. , Coggin R. R. , Roby J. , Feezor M. , Turner G. , Bennett P. B.
Published: December 2017

A liquid-breathing apparatus is described for remote surface studies and for use in experiments of near-hydraulic compression in dogs. It consists of a flexible tank sealed against chamber gas, containing a supply of clean warmed (38 degrees C) fluorocarbon (FC-80) equilibrated with 1 bar O2 and an electronically controlled means of delivering the liquid to the dog. Each breath (tidal volume 290 ml) was “weighed” into the animal by the signal from a force platform supporting the dog and a digital control unit that automatically actuated inspired-and expired-line solenoid valves. The apparatus was successfully used to remotely maintain liquid ventilation in awake dogs for 2 h during surface studies (5 dogs) and in dives to 1,000 m seawater (5 dogs). During liquid breathing, mean arterial O2 partial pressure was always adequate (congruent to 300 Torr) and mean arterial CO2 partial pressure was normal (less than or equal to 40 Torr). An uncompensated metabolic acidosis was indicated by low pH values and a decrease in arterial base excess to--4.5 meq x 1(-1). O2 uptake and CO2 output appeared to be significantly lower (42 and 35%, respectively) during liquid ventilation.
Measurement of ventilation using digitally filtered transthoracic impedance
Authors: Newton P. E. , Hamilton L. H. , Forster H. V.
Published: December 2017

A seven-stage low-pass digital filter was used to remove the cardiac artifact and motion interference from a respiratory transthoracic impedance signal in human subjects. After removal of these artifacts, the mean difference from a conventional gasometer technique fell from 5% to 1.6%. When the impedance technique was used to measure ventilation during air breathing, the addition of a breathing valve with a mouthpiece and noseclip induced the following changes in ventilatory parameters: 7% drop in frequency, 24% increase in tidal volume, 49% increase in inspiratory time, 56% increase in expiratory time, 10% decrease in inspiratory flow rate, and 4% decrease in ratio of respiratory time to total breath duration. These alterations were not significant at elevated inspired CO2 levels. The digitally filtered transthoracic impedance technique provides an accurate technique for measuring ventilatory parameters without the perturbations induced by using a conventional breathing valve technique even when cardiac and motion artifacts were prominent.
Sexual influence on the control of breathing
Authors: White D. P. , Douglas N. J. , Pickett C. K. , Weil J. V. , Zwillich C. W.
Published: December 2017

Previous investigation has demonstrated that progesterone, a hormone found in premenopausal women, is a ventilatory stimulant. However, fragmentary data suggest that normal women may have lower ventilatory responses to chemical stimuli than men, in whom progesterone is found at low levels. As male-female differences have not been carefully studied, we undertook a systematic comparison of resting ventilation and ventilatory responses to chemical stimuli in men and women. Resting ventilation was found to correlate closely with CO2 production in all subjects (r = 0.71, P less than 0.001), but women tended to have a greater minute ventilation per milliliter of CO2 produced (P less than 0.05) and consequently a lower CO2 partial pressure (PCO2) (men 35.1 +/- 0.5 Torr, women 33.2 +/- 0.5 Torr; P less than 0.02). Women were also found to have lower tidal volumes, even when corrected from body surface area (BSA), and greater respiratory frequency than comparable males. The hypoxic ventilatory response (HVR) quantitated by the shape parameter A was significantly greater in men [167 +/- 22 (SE)] than in women (109 +/- 13; P less than 0.05). In men this hypoxic response was found to correlate closely with O2 consumption (r = 0.75, P less than 0.001) but with no measure of size or metabolic rate in women. The hypercapnic ventilatory response, expressed as the slope of ventilation vs. PCO2, was also greater in men (2.30 +/- 0.23) than in women (1.58 +/- 0.19, P less than 0.05). Finally women tended to have higher ventilatory responses in the luteal than in the follicular menstrual phase, but this was significant only for HVR (P less than 0.05). Women, with relatively higher resting ventilation, have lower responses to hypoxia and hypercapnia.
Effects of beta-adrenergic blockade on O2 uptake during submaximal and maximal exercise
Authors: Tesch P. A. , Kaiser P.
Published: December 2017

Changes in cardiorespiratory variables and perceived rate of exertion (RPE) were studied in 13 trained men performing cycling exercise before and after beta-adrenergic blockade. Propranolol (Inderal, 80 mg) was administered orally 2 h prior to standardized maximal and submaximal exercises. Muscle biopsies were obtained from vastus lateralis at rest for subsequent histochemical analyses of muscle fiber type distribution and capillary supply. During submaximal exercise O2 consumption decreased from 2.76 to 2.59 l . min-1 following blockade (P less than 0.01), whereas heart rate decreased from 157 to 113 beats . min-1 (P less than 0.001). Maximal O2 uptake was lowered from 3.79 to 3.26 l . min-1 (P less than 0.001) and maximal heart rate was reduced from 192 to 142 beats . min-1 (P less than 0.001) as a result of the blockade. Pulmonary ventilation was unaltered in both exercise conditions. “Local” RPE was higher (P less than 0.001) than “central” RPE after beta-blockade in both submaximal and maximal exercise. During normal condition this difference did not appear. Changes in both local and central RPE during submaximal exercise were positively correlated to changes in O2 uptake. Individual variations in the metabolic profile of the exercising muscle had no influence on beta-blockade-induced changes in O2 uptake. It is concluded that blockade of beta-adrenergic receptors reduces O2 consumption during submaximal (approximately 73% maximal O2 uptake) and maximal exercise in habitually trained men.
Characteristics of airway tone during exercise in patients with asthma
Authors: Stirling D. R. , Cotton D. J. , Graham B. L. , Hodgson W. C. , Cockcroft D. W. , Dosman J. A.
Published: December 2017

In 10 nonasthmatic subjects and 11 patients with asthma, we measured pulmonary resistance (RL), functional residual capacity (FRC), and specific conductance (sGaw) before, during, and after submaximal treadmill exercise. Nonasthmatic subjects did not change RL, FRC, or sGaw from base-line resting values during or after exercise. In patients with asthma, RL decreased significantly during exercise, both when exercise was begun from the control resting state and from conditions of elevated RL after a preceding period of exercise. When asthmatic patients inhaled a standardized dose of aerosolized histamine, the increase in RL during exercise was significantly less than the increase in RL when they breathed histamine at rest. When patients hyperventilated at rest with tidal volumes, breathing frequencies, and end-tidal CO2 tensions similar to those during exercise conditions, bronchodilatation also occurred, and the increase in RL following inhaled histamine during isocapnic hyperventilation was also less than at rest. Since bronchodilatation and inhibition of histamine-induced bronchoconstriction occur during both exercise and isocapnic hyperventilation, we suggest that the mechanism of bronchodilatation during exercise may not necessarily be related to metabolic factors associated with exercise.
Augmentation of cardiac function by elevation of intrathoracic pressure
Authors: Pinsky M. R. , Summer W. R. , Wise R. A. , Permutt S. , Bromberger-Barnea B.
Published: December 2017

We studied the cardiovascular effects of increasing intrathoracic pressure in an acute pentobarbital-anesthetized canine model of acute ventricular failure induced by large doses of propranolol. Left ventricular (LV) function curves were generated by volume loading from LV filling pressures of 5–20 Torr. The animals were ventilated by using intermittent positive-pressure ventilation with large tidal volumes (30 ml/kg). Chest and abdominal pneumatic binders were used to increase intrathoracic pressure. When compared with the control state, acute ventricular failure was associated with a decrease in the slope of the LV function curves (P less than 0.01). After binding the increase in intrathoracic pressure (1.1 +/- 1.6 to 12.1 +/- 2.4 Torr, P less than 0.01) was associated with an improvement in both right ventricular and LV function. Our study demonstrates that in this model of acute ventricular failure, increasing intrathoracic pressure improves cardiac function. We postulate that this observed improvement with increased intrathoracic pressure is due to reduced LV wall stress in a manner analogous to that seen with arterial vasodilator therapy in congestive heart failure.
Acid-base curve and alignment nomograms for swine blood
Authors: Weiskopf R. B. , Townsley M. I. , Riordan K. K. , Harris D. , Chadwick K.
Published: December 2017

To construct acid-base curves and alignment nomograms for swine blood, we added known amounts of acid or base to aliquots of swine blood with three different concentrations of hemoglobin. Pairs of blood samples were equilibrated at two different CO2 partial pressures, and blood pH was measured. Data were analyzed by computer, and mean values were created for complete data of four swine. Curve and alignment nomograms were constructed by computer. The resultant nomograms for swine blood differ from those constructed by Siggaard-Andersen for human blood, most importantly at base-excess values of +10 to +25 mmol/l. The possible reasons for the observed differences are discussed and, although not completely resolved, may be related in large measure to the accuracy of pH determination and the methodology of nomogram construction.
Role of lymphatics in removal of sheep lung surfactant lipid
Authors: Tarpey M. M. , O'Brodovich H. M. , Young S. L.
Published: December 2017

To study the role of lung lymphatics in the removal of surfactant lipid from the sheep lung, we injected [1–14C]palmitate intravenously into six animals previously fitted with a cannula draining the caudal mediastinal lymph node. Lung lymph was collected for 100 h after injection of radiolabel. We obtained alveolar lavage material through a tracheostomy in four other animals after intravenous injection of [9,10–3H]palmitate. We measured radioactivity at several time points in lipid extracts from lymph, lavage fluid, and lung tissue. Alveolar lavage disaturated phosphatidylcholine (DSPC) specific activity peaked at about 40 h and was reduced to 30% of this value by 82 h. About 2% of the injected radiolabel was incorporated into lung tissue lipids. Only 4% of the level of labeling achieved in lung tissue lipids was found in lung lymph lipid during 100 h of lymph collection. Sixty-three percent of radiolabel in lymph lipid was recovered in phospholipids, and 29% of phospholipid radiolabel was found in DSPC. The distribution of phosphorus and palmitate radiolabel in lung lymph phospholipid did not closely resemble that of surfactant lipid. No rise in lung lymph DSPC specific activity was observed following the peak in lavage specific activity. If surfactant lipid is removed from the alveolar compartment without extensive recycling, then we conclude that the lung lymphatics do not play a major role in the clearance of surfactant lipid from the alveolar surface.
Movement of CO2 and HCO-3 from blood to brain in dogs
Authors: Johnson D. C. , Hoop B. , Kazemi H.
Published: December 2017

The ratio of carbon dioxide (CO2) to bicarbonate (HCO-3) is important in acid-base homeostasis and to the central chemical drive to ventilation. The entry of HCO-3 from blood into the central nervous system (CNS) has been controversial, and the entry of CO2, assumed to be rapid, has not been separated from HCO-3 entry. Therefore the rates of movement of CO2 and of HCO-3 from blood to CNS were evaluated. The first-pass brain uptake of 11C-labeled CO2-HCO-3 was studied under conditions with and without carbonic anhydrase inhibition (CAI), with the isotope injected either as CO2 (acid injectate) or as HCO-3 (alkaline injectate) into the aortic arch of anesthetized dogs. The uptake of 11C under conditions without CAI was about 80% and remained the same whether the isotope was injected as CO2 or as HCO-3. The uptake of 11C under conditions of cerebroventricular administration of acetazolamide was 61.5 +/- 2.0% after injection as CO2 and 56.7 +/- 8.3% after injection as HCO-3. The uptake of 11C under conditions of systemic CAI was 50.3 +/- 3.0% after injection as CO2 and 19.3 +/- 1.1% after injection as HCO-3. The uptakes were comparable for the combination of cerebroventricular and intravenous acetazolamide. From the values for 11C uptake with systemic CAI and the uncatalyzed reaction rates for interconversion of CO2 and HCO-3, the first-pass brain uptake was calculated to be 87.7 +/- 7.8% for CO2 and 16.3 +/- 1.8% for HCO-3. Thus there is a very rapid diffusion of CO2 from blood to brain and a significant movement of HCO-3 from blood to brain.
A perspective of respiratory mechanics
Authors: Otis A. B.
Published: December 2017

Breathing was recognized very early to be a muscular action. The participation of the diaphragm, intercostals, and accessory muscles was appreciated by Galen. Consideration of a possible role for smooth muscle in breathing did not occur until much later. Even today smooth muscle is seldom included as a topic in discussions of “respiratory mechanics.” Bronchial smooth muscle was first described in the classic study of Reisseisen in the early 19th century, although the presence of contractile elements in lungs had been demonstrated a few decades previously. An important comprehensive investigation of the action of bronchial smooth muscle was published in 1892 by Willem Einthoven. His experimental approach became a paradigm. On the other hand, his analysis of dynamic collapse of the airways received little attention and was independently arrived at half a century later. Although we now have a considerable understanding of the mechanics of bronchial smooth muscle and of the effects of numerous physiological and pharmacological agents on its behavior, the exact role it plays in normal physiological function is unclear. Numerous plausible suggestions have been made, but none has been convincingly demonstrated.
Dysanaptic lung growth: an experimental and allometric approach
Authors: Mortola J. P.
Published: December 2017

The postnatal development of the mammalian lung, which at birth has only a fraction of the adult number of alveoli, would suggest a mismatch (dysanapsis) of the changes in airway size and lung size with growth. This may have implications on the efficiency of breathing because for any given lung size the dimensions of the airways are the determinant of the amount of dead space (VD) ventilation and of airflow resistance. A comparison of the allometric functions of tracheal dimensions previously published suggests that the tracheal volume, taken as representative of VD, is smaller in newborns than in adults. This difference becomes more apparent when examined per unit of functional residual capacity (VD/FRC). The relatively smaller tracheal volume is the result of both a shorter and narrower trachea in the newborn. This latter difference implies a slightly but significantly higher resistance of the lower airways, as also demonstrated by experimental measurements of peak expiratory flows at a constant driving pressure in rats of different ages. Because the slightly higher resistance of the lower airways is probably compensated by the smaller resistance of the upper airways (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 51: 641–645, 1981), it would seem that the structure of the newborn mammalian lung favors the alveolar ventilatory function without a substantial increase of the energetic losses.
Measurement of arterial blood gases at the transition from exercise to rest
Authors: Lewis B. M.
Published: December 2017

Arterial blood gas samples obtained 5–20 s after stair-climbing exercise were compared with samples taken during the last 30 s of exercise in 137 subjects. Arterial partial pressure of CO2 (PaCO2) did not change significantly, and in 110 subjects the two samples were within the analytical variation (+/- 2 Torr), supporting the cardiodynamic hypothesis of respiratory regulation. Exceptions to this response were 10 subjects who hyperventilated (PaCO2 less than 34) during exercise and 15 with severe obstruction [forced expiratory volume in 1 s (FEV1) less than 70% forced vital capacity (FVC), and FVC less than 70% of predicted] in whom PaCO2 increased significantly. Overall, arterial partial pressure of O2 (PaO2) increased an average of 3.49 Torr (P less than 0.001). In the two groups in which PaCO2 increased, postexercise PaO2 did not rise. In addition, duration of exercise affected PaO2 response. PaO2 increased significantly more after brief (less than 2 min) periods than after longer (4–6 min) exercise, and this difference increased only when subjects with normal or borderline ventilatory function were analyzed. In 13 subjects in whom a second sample was taken 30–45 s after exercise, the increase in PaO2 was progressive and again the difference between short and long exercise was evident. Regulation of respiration to maintain PaCO2 and changes in O2-CO2 kinetics, leading to an increase in the gas exchange ratio at the exercise-rest transition, are the most likely explanations of these data which establish that the usual response to stopping exercise in normal subjects and most patients is an unchanged PaCO2 and a variable increase in PaO2.
Pulmonary effects of ozone exposure during exercise: dose-response characteristics
Authors: McDonnell W. F. , Horstman D. H. , Hazucha M. J. , Seal E. , Haak E. D. , Salaam S. A. , House D. E.
Published: December 2017

Because minimal data are available regarding the pulmonary effects of ozone (O3) at levels less than 0.27 ppm, six groups of healthy young males were exposed for 2.5 h to one of the following O3 concentrations: 0.0, 0.12, 0.18, 0.24, 0.30, or 0.40 ppm. Fifteen-minute periods of rest and exercise (65 l/min minute ventilation) were alternated during the first 2 h of exposure. Coughing was observed at all levels of O3 exposure. Small changes in forced-expiratory spirometric variables [forced vital capacity (FVC), forced expiratory volume in 1 s, and mean expiratory flow rate between 25 and 75% FVC] were observed at 0.12 and 0.18 ppm O3, and larger changes were found at O3 levels greater than or equal to 0.24 ppm. Changes in tidal volume and respiratory frequency during exercise, specific airway resistance, the presence of pain on deep inspiration, and shortness of breath occurred at O3 levels greater than or equal to 0.24 ppm. In conclusion, pulmonary effects of O3 were observed at levels much lower than that for which these effects have been previously described. Stimulation of airway receptors is probably the mechanism responsible for the majority of observed changes; however, the existence of a second mechanism of action is postulated.
Effect of beta-adrenergic blockade on hyperventilation and exercise tolerance in emphysema
Authors: Butland R. J. , Pang J. A. , Geddes D. M.
Published: December 2017

Ventilation, heart rate, and arterial blood gas tensions were measured at rest and during incremental exercise in 10 patients with emphysema after intravenous placebo or 7 mg metoprolol. Metoprolol reduced heart rate by 14% (P less than 0.001) and ventilation by 11% (P less than 0.01), but there was no significant difference in arterial O2 or CO2 tension (Pao2 and PaCO2, respectively). Metoprolol increased the time to exhaustion on a cycle ergometer (P less than 0.05) but did not improve the 12-min walking distance. A double-blind randomized crossover comparison of 4 wk treatment with atenolol (100 mg/day), metoprolol (100 mg/day), or matched placebo was performed in 12 patients with emphysema. Both beta-adrenoceptor antagonists reduced resting heart rate by 33% (P less than 0.001) and resting minute ventilation by 11% (P less than 0.025). There was no change in resting or exercise Pao2 or Paco2. During steady-state exercise on a cycle ergometer, atenolol and metoprolol reduced ventilation by 14 and 4%, respectively. This was accompanied by 11 and 5% reductions in O2 consumption (P less than 0.05) and 13 and 6% falls in CO2 production (P less than 0.05). There were no significant changes in tests of exercise tolerance, but forced expiratory volume in 1 s and forced vital capacity were reduced during beta 1-adrenergic blockade. beta 1-Blocking drugs reduce hyperventilation in emphysema by reducing pulmonary gas exchange without a change in arterial blood gas tensions. Increased airflow obstruction prevents this reduction being of therapeutic value.