bluuebunny/crossref_metadata_2025 huggingface dataset:
Heterogeneity in the effects of epithelium removal in the canine bronchial tree
Authors: Stuart-Smith K. , Vanhoutte P. M.
Published: December 2017

The effect of removing the airway epithelium on the responses of canine airways of decreasing diameter to contractile and relaxing agonists was explored. Three orders of canine bronchus were studied: second order (lobar bronchus), third order (segmental bronchus), and fourth order (subsegmental bronchus). Paired rings of tissue, with and without epithelium, were placed in organ chambers in physiological salt solution gassed with 95% O2–5% CO2 and maintained at 37 degrees C. For second- and third-order bronchi, epithelium removal caused significant left-ward shifts of the concentration-effect curves for 5-hydroxytryptamine, histamine, and acetylcholine. In fourth-order bronchi, there was no significant shift for any of the contractile agonists. Isoproterenol (during contractions evoked by acetylcholine) induced concentration-dependent relaxations that were significantly greater in bronchi with than in those without epithelium. This effect was most prominent in fourth-order bronchi. These results suggest that 1) the canine airway epithelium releases a relaxing factor, 2) in larger airways the major effect is reduction of contractile responses, and 3) in smaller airways the major effect is enhancement of relaxing responses.
Effects of intracellular pH on hypoxic vasoconstriction in rat lungs
Authors: Raffestin B. , McMurtry I. F.
Published: December 2017

Isolated rat lungs perfused with physiological salt-Ficoll solutions were studied to test whether hypoxic pulmonary vasoconstriction was potentiated by increases in intracellular pH (pHi) and blunted by decreases in pHi. Whereas addition to perfusate of 5 nM phorbol myristate acetate (PMA), a stimulator of exchange of intracellular H+ for extracellular Na+, potentiated hypoxic vasoconstriction, 1 mM amiloride, an inhibitor of Na+-H+ exchange, blunted the hypoxic response. Hypoxic vasoconstriction was also potentiated by the weak bases NH4Cl (20 mM), methylamine (10 mM), and imidazole (5 mM) and was inhibited by the weak acid sodium acetate (40 mM). NH4Cl, imidazole, and acetate had the same effects on KCl-induced vasoconstriction and on the hypoxic response. Hypoxic vasoconstriction was greater in lungs perfused with N-2-hydroxyethylpiperazine-N′-2-ethanesulfonic acid (HEPES)-buffered solution than in those perfused with CO2/HCO3--buffered solution. Similarly, lungs perfused with CO2/HCO3--buffered solution containing 1.8 mM Cl- (NaNO3 and KNO3 substituted for NaCl and KCl) had larger hypoxic and angiotensin II pressor responses than those perfused with 122.5 mM Cl-. Because PMA, NH4Cl, methylamine, imidazole, HEPES-buffered solutions, and low-Cl- solutions can cause increases in pHi and amiloride and acetate can cause decreases in pHi, these results suggest that intracellular alkalosis and acidosis, respectively, potentiate and blunt vasoconstrictor responses to hypoxia and other stimuli in isolated rat lungs. These effects could be related to pHi-dependent changes in either the sensitivity of the arterial smooth muscle contractile machinery to Ca2+ or the release of a vasoactive mediator or modulator by some other lung cell.
Effects of water immersion on arginine vasopressin release in humans
Authors: Norsk P. , Epstein M.
Published: December 2017

Since suppression of arginine vasopressin (AVP) appears to be a determinant of the diuresis of water immersion (WI) in humans, a further understanding of its responsiveness has important implications for normal physiology, pathophysiology, and space physiology. In recent years, discrepant measurements of AVP in plasma during WI have led to conflicting conclusions. In studies in which the subjects ingested water before or during WI, plasma AVP was reported to be unchanged or even increased. In contrast, plasma AVP was suppressed in studies in which the subjects remained hydropenic. A critical review discloses that water intake before and/or during the experiments introduces several new stimuli for AVP release. Furthermore the lower base-line levels of AVP in hydrated subjects complicate detection of small changes in plasma AVP. Although the mechanisms of AVP suppression during WI are incompletely defined, it appears that not only cardiopulmonary mechanoreceptors but also arterial baroreceptors mediate the response. Additional studies are proposed to delineate further the mechanisms governing AVP release during WI.
Effect of body posture on respiratory impedance
Authors: Navajas D. , Farre R. , Rotger M. M. , Milic-Emili J. , Sanchis J.
Published: December 2017

The effects of posture on the mechanics of the respiratory system are not well known, particularly in terms of total respiratory resistance. We have measured respiratory impedance (Zrs) by the forced random noise excitation technique in the sitting and the supine position in 24 healthy subjects. Spirometry and lung volumes (He-dilution technique) were also measured in both postures. The equivalent resistance (Rrs), compliance (Crs), and inertance (Irs) were also calculated by fitting each measured Zrs to a linear series model. When subjects changed from sitting to the supine position, the real part of Zrs increased over the whole frequency band. The associated equivalent resistance, Rrs, increased by 28.2%. The reactance decreased for frequencies lower than 18 Hz and increased for higher frequencies. Consequently, Crs decreased by 38.7% and Irs increased by 15.6%. All of these parameter differences were significant (P less than 0.001). A covariance analysis showed that a significant amount of the postural change in Rrs and Crs can be explained by the reduction of functional residual capacity (FRC). This indicates that the observed differences on Zrs can in part be explained be a shift of the operating point of the respiratory system induced by the decrease in the FRC.
Breathing patterns in anesthetized cats and the concept of minimum respiratory effort
Authors: Luijendijk S. C. , Milic-Emili J.
Published: December 2017

Theoretical studies dealing with the principle of minimal respiratory effort usually make use of sinusoidal or saw-tooth-like breathing patterns. Recent observations in anesthetized cats have shown that the driving pressure waveform for inspiration can be described by a power function of time and that most of expiration is passive. This driving pressure waveform, however, results in breathing patterns that differ from those described above. For this reason, we have reevaluated in anesthetized cats the principle of minimal respiratory effort by computing optimal duration of inspiration (TI) and optimal tidal volume (VT) for different ventilatory conditions using actual driving pressure waveforms. The results are in qualitative agreement with the experimental observations; i.e., optimal TI decreases and optimal VT increases with increasing minute ventilation. On the average, a good agreement is found between measured and computed values of TI. In some cats, however, there are substantial differences between observed and predicted values of TI, which can probably be ascribed to inaccuracies in the data used in our computations. Despite its limitations, the present model analysis is more realistic than previous ones because actual driving pressure waveforms are used together with actual values of effective inspiratory impedance.
Cholinergic responsiveness of respiratory and vascular tissues in two different rat strains
Authors: Badier M. , Soler M. , Mallea M. , Delpierre S. , Orehek J.
Published: December 2017

The airway and systemic arterial smooth muscle responsiveness to cholinergic agents of two strains of rats, Rat Albino (RA) and Brown Norway (BN), was compared in vivo and in vitro. In vivo, we measured the doses of carbachol that induced a 100% increase in lung resistance (PD100 RL), a 50% decrease in dynamic lung compliance (PD50 Cdyn), and the value of systolic blood pressure at the carbachol dose of 10 micrograms (Pa 10 micrograms). In vitro airway smooth muscle and systemic arterial smooth muscle responsiveness was assessed by measuring the maximal response to acetylcholine, the slope of the linear portion of the dose-response curve, and the negative logarithm of the molar concentration of acetylcholine producing 50% of the maximal response (pD2). PD100 and PD50 were about four times greater in BN rats than in RA rats. In contrast, Pa 10 micrograms was 1.5 lower in the BN rats. These differences persisted after bivagotomy. Tracheal pD2 was 25% greater in the RA than in the BN strain. The mean dose-response curve of parenchymal strips of RA rats was situated upward and to the left of the BN curve, but the reverse was observed for aortic smooth muscle dose-response curves. Thus 1) airway smooth muscle responsiveness to cholinergic agents is greater in RA strain than in BN, but the reverse is true for systemic arterial smooth muscle responsiveness; and 2) these differences are not due to factors extrinsic to the smooth muscle, since they occurred in vitro and may depend on different densities of muscarinic receptors.
Effect of lung volume on interrupter resistance in cats challenged with methacholine
Authors: Sly P. D. , Brown K. A. , Bates J. H. , Macklem P. T. , Milic-Emili J. , Martin J. G.
Published: December 2017

To examine the effects of changes in lung volume on the magnitude of maximal bronchoconstriction, seven anesthetized, paralyzed, tracheostomized cats were challenged with aerosolized methacholine (MCh) and respiratory system resistance (Rss) was measured at different lung volumes using the interrupter technique. Analysis of the pressure changes following end-inspiratory interruptions allowed us to partition Rss into two quantities with the units of resistance, one (Rinit) corresponding to the resistance of the airways and the other (Rdif) reflecting the viscoelastic properties of the tissues of the respiratory system as well as gas redistribution following interruption of flow. Rinit and Rdif were used to construct concentration-response curves to MCh. Lung volume was increased by the application of 5, 10, and 15 cmH2O of positive end-expiratory pressure. The curve for Rinit reached a plateau in all cats, demonstrating a limit to the degree of MCh-induced bronchoconstriction. The mean value of Rinit (cmH2O.ml-1.s) for the group under control conditions was 0.011 and rose to 0.058 after maximal bronchoconstriction; the volume at which the flow was interrupted was 11.5 +/- 0.5 (SE) ml/kg above functional residual capacity (FRC). It then fell progressively to 0.029 at 21.2 +/- 0.8 ml/kg above FRC, 0.007 at 35.9 +/- 1.3 ml/kg above FRC, and 0.005 at 52.0 +/- 1.8 ml/kg above FRC. Cutting either the sympathetic or parasympathetic branches of the vagi had no significant effect on the lung volume-induced changes in MCh-induced bronchoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)
Kinetics of VO2 with impulse and step exercise in humans
Authors: Hughson R. L. , Sherrill D. L. , Swanson G. D.
Published: December 2017

The constancy of the time course (i.e., dynamic linearity) of the O2 uptake (VO2) response to exercise was examined by testing the law of superposition on data from impulse and step work rate forcings. Two impulses (10 s at a 235-W increase above a 25-W base line, I-235; and 5 s at a 475-W increase above a 25-W base line, I-475), four steps (ST) (25-65 W, ST1; 65-105 W, ST2; 25-105 W, ST3; and 25-145 W, ST4), and the corresponding off-transient responses were performed six to eight times by each of five subjects. The integrated area (G) of the VO2 response for I-235 was similar to that of ST1 and ST2 (P greater than 0.05); the I-475 G was significantly greater (P less than 0.05). The time constant of VO2 during the step function on-transient response for the second exponential component was significantly faster for ST1 and significantly slower for I-235 and I-475 than for ST2, ST3, and ST4 (P less than 0.05). However, I-235 and I-475 time constants for VO2 were not different from the ST off-transient values. Attempts to superimpose the integral of the impulse on the ST data showed that the early rapid increase in VO2 in the ST was underpredicted by the impulse and that the impulse response lagged behind the ST at all points before steady state. It can be concluded that VO2 kinetics failed the test of superposition and are therefore described by a nonlinear dynamic system.
Effect of changing lung liquid volume on the pulmonary circulation of fetal lambs
Authors: Walker A. M. , Ritchie B. C. , Adamson T. M. , Maloney J. E.
Published: December 2017

During fetal life the lung develops as a liquid-filled structure with low blood flow compared with postnatal life. We studied the effects of liquid expansion of the fetal lung by measuring vascular conductance in perfused lungs in situ and arterial diameters in excised lungs of fetal lambs. Pulmonary vascular conductance invariably rose as the lung was deflated from its initial volume; maximal deflation to residual volume increased conductance 122%. With reexpansion, conductance fell progressively, culminating in cessation of flow at lung volumes of twice the initial volume. These changes persisted after vagotomy and thoracic sympathectomy and therefore were mechanical in character. Lung expansion from residual volume initially expanded 300- to 500-micron arteries but compressed arteries greater than 1,500 micron. Further expansion reduced the caliber of all arteries. Thus increasing lung liquid volume progressively constricts the pulmonary circulation in the fetus. Because the fetal pulmonary vascular resistance-lung volume relationship differs from that of the U-shaped form found in adult lungs, concepts based on the adult pulmonary circulation are not appropriate for liquid-filled fetal lungs.
Reliability and validity of bioelectrical impedance in determining body composition
Authors: Jackson A. S. , Pollock M. L. , Graves J. E. , Mahar M. T.
Published: December 2017

This study was designed to examine the reliability and validity of the bioelectrical impedance method (BIA) of measuring body composition and compare its accuracy with the results obtained by standard anthropometric methods BIA, skinfold fat, and hydrostatically measured percent fat (% fat) were obtained on 44 women and 24 men. Each subject was tested four times by two testers on two different days. Generalizability theory was used to estimate reliability and measurement error that considered both day-to-day and intertester error. The BIA, skinfold fat, and hydrostatic methods were all found to be reliable (Rxx = 0.957–0.987) with standard errors ranging from 0.9 to 1.5% fat. An additional 26 men (n = 50) and 38 women (n = 82) were tested once and combined with the data used for the reliability analysis to cross-validate BIA estimates of % fat with hydrostatically determined % fat. The cross-validation correlations for the BIA determinations of % fat ranged from 0.71 to 0.76, which were significantly lower than that obtained with the sum of seven (sigma 7) skinfolds equations (rxy = 0.92 for men and 0.88 for women). The correlations between the weight-to-height ratio body mass index (BMI) and hydrostatically determined % fat were 0.75 and 0.74 for men and women, respectively. The standard errors of estimate for the two BIA models ranged from 4.6 to 6.4% fat compared with 2.6 and 3.6% fat for the sigma 7 equations. The BIA method for measuring body composition was comparable to the BMI method, with height and weight accounting for most of the variance in the BIA equation.
Mechanical coupling of upper and lower canine rib cages and its functional significance
Authors: Jiang T. X. , Demedts M. , Decramer M.
Published: December 2017

We studied rib cage distortability and reexamined the mechanical action of the diaphragm and the rib cage muscles in six supine anesthetized dogs by measuring changes in upper rib cage cross-sectional area (Aurc) and changes in lower rib cage cross-sectional area (Alrc) and the respective pressures acting on them. During quiet breathing in the intact animal the rib cage behaved as a unit (Aurc: 14.6 +/- 7.9 vs. Alrc: 15.1 +/- 9.6%), whereas considerable distortions of the rib cage occurred during breathing after bilateral phrenicotomy (Aurc: 21.0 +/- 5.1 vs. Alrc: 7.0 +/- 4.8%). These distortions were even more pronounced during phrenic nerve stimulation and separate stimulation of the costal and crural parts of the diaphragm (e.g., phrenic nerve stimulation; Aurc: -7.1 +/- 5.1 vs. Alrc: 6.9 +/- 3.5%). During the latter maneuvers the upper rib cage deflated along the relationship between upper rib cage dimensions and pleural pressure obtained during passive deflation, whereas the lower rib cage inflated close to the relationship between lower rib cage dimensions and abdominal pressure obtained during passive inflation. The latter relationship is expected to differ between costal and crural stimulation, since costal action has both an appositional and insertional component and crural action only has an appositional component. The difference between costal and crural stimulation, however, was relatively small, and the slopes were only slightly steeper for the costal than for the crural stimulation (2.9 +/- 1.2 vs. 2.2 +/- 1.0%.(ABSTRACT TRUNCATED AT 250 WORDS)
Bolus technique for assessing distribution of inspired gas during tidal breathing
Authors: Arita K. I. , Lewis S. M. , Mittman C.
Published: December 2017

The washout of an insoluble tracer from the lung may be represented by a model with two ventilatory compartments representing poorly and better-ventilated regions. Using boli of a second insoluble gas delivered at a given point during inspirations of a multibreath washout test, the proportions of labeled inspired ventilation reaching the poorly and well-ventilated regions may be determined by analyzing the kinetics of the exhaled tracer. We studied eight normal subjects breathing through large-bore solenoid valves controlled to maintain tidal volume at 600 or 900 ml. Boli consisting of 15 ml of 80% He-20% O2 were delivered over 75 ms; this labeled approximately 125 ml of inspired gas. Boli were delivered after 50 ml had been inspired to mark early inspiration and after 300 ml had been inspired to mark midinspiration. Using 900-ml tidal breaths, late inspiration was marked by boli delivered at 600 ml. Subjects were studied in the seated and the supine positions. In both positions, significantly more of the early breath went to the poorly ventilated compartment. Several possible physiological mechanisms, singly or in combination, could account for these observations, but differences in dead space path length are most likely involved.
Enhancement of pulmonary inflammation by PGE2: evidence for a vasodilator effect
Authors: Downey G. P. , Gumbay R. S. , Doherty D. E. , LaBrecque J. F. , Henson J. E. , Henson P. M. , Worthen G. S.
Published: December 2017

We explored the potential proinflammatory effect of prostaglandins of the E series (PGE's) in a rabbit model of acute pulmonary inflammation. The instillation of fragments of the fifth component of complement (C5f) into the lung resulted in a localized area of inflammation, the extent of which was quantified by the total number of neutrophils and protein recoverable by bronchoalveolar lavage (BAL). Utilizing 111In-labeled neutrophils and serial scintigraphy, neutrophil localization in the area of inflammation was detected as early as 20 min after C5f instillation and reached a maximum between 2 and 4 h. The simultaneous intrabronchial administration of 100 micrograms of PGE2 resulted in a twofold increase in the accumulation of neutrophils in the area of inflammation as determined scintigraphically, a fivefold increase in BAL neutrophils, and a threefold increase in BAL protein. A proinflammatory effect on lavage constituents was also seen with the intravenous administration of PGE2 (100 ng.kg-1.min-1) and PGE1 (50 ng.kg-1.min-1) as well as in animals pretreated with a PGH synthase inhibitor, meclofenamate, and a thromboxane synthase inhibitor, dazmegrel. The effect of intrabronchial PGE2 to potentiate the inflammatory response was attenuated by the intravenous administration of a vasoconstrictor (angiotensin II) and mimicked by a vasodilator (nitroprusside), suggesting an effect of vasodilation per se. Using radiolabeled microspheres, it was determined that in response to the C5f alone, there was a 50% decrease in local blood flow to the area of inflammation, a pattern different from that seen in the systemic circulation. This decrease was prevented by the concomitant administration of PGE2 or nitroprusside. We conclude that vasodilation induced by PGE2 is associated with enhancement of pulmonary inflammation.
Effects of meclofenamate on breathing movements in fetal sheep before delivery
Authors: Wallen L. D. , Murai D. T. , Clyman R. I. , Lee C. H. , Mauray F. E. , Kitterman J. A.
Published: December 2017

There is evidence that prostaglandins (PG), specifically PGE2, participate in the regulation of fetal breathing movements (FBM). During late gestation, when FBM occur intermittently and primarily during low-voltage electrocortical activity, the concentration of PGE2 in fetal plasma ([PGE2]) is high. During the days before delivery [PGE2] increases and FBM decrease. To determine whether the increase in [PGE2] is responsible for the concurrent decrease in FBM, we infused the prostaglandin synthase inhibitor, meclofenamate (0.7 mg.kg-1.h-1), into eight fetal sheep continuously for 5-–13 days before delivery; five control fetuses received a continuous infusion of the solvent for 5–11 days before delivery. Compared with control infusion, meclofenamate caused a significant decrease in [PGE 2] until the day of delivery and a significant increase in FBM [overall and during high-voltage electrocortical activity (HVA)] until 2 days before delivery. Although there were significant correlations between [PGE2] and FBM (overall and during HVA), both groups showed similar decreases in FBM during the 2 days before delivery. We conclude that the decrease in FBM before delivery is not dependent on the concurrent increase in [PGE2].
Analysis of linear and mildly nonlinear relationships using pooled subject data
Authors: Poon C. S.
Published: December 2017

The detection of mild nonlinearities and/or state-dependent variability in otherwise linear physiological relationships is generally difficult in the presence of significant measurement errors. Conventional approaches using pooled subject data to increase the degree of freedom for statistical inference are enervated by the resultant introduction of intersubject variability. This paper proposes a new, simple method of pooling multiple subject data for linearity analysis. With the use of a special standardization procedure for the individual response curves, this method allows sensitive detection of occult nonlinearities as well as any state-dependent variability in the underlying relationship. Application of this analytic approach to reported hypercapnic exercise-response data in eight healthy subjects showed that 1) the hypercapnic ventilation-CO2 output relationship is nonlinear with a downward concavity; and 2) the ventilation-tidal volume relationship, which is linear at low tidal volume values, is similar in hypercapnic exercise as in resting hypercapnia or eucapnic exercise.
Lung microvascular pressure profile measured by micropuncture in anesthetized dogs
Authors: Shepard J. M. , Gropper M. A. , Nicolaysen G. , Staub N. C. , Bhattacharya J.
Published: December 2017

We have micropunctured the lung in the open thorax of 17 anesthetized dogs to measure microvascular pressure. After intravenous pentobarbital sodium (25 mg/kg), we exposed the left lung through a wide left thoracotomy, which required rib excision. Through a double-lumen endotracheal tube, we ventilated the right lung to maintain normal blood gases and pH while we held the left lung motionless at an inflation pressure of 5 cmH2O. To reduce motion on the surface of the left lower lobe, we resected the left upper lobe, placed a Plexiglas baffle between the lobe and the heart, and held the lobe surface in a suction ring. In accordance with procedures we have previously described, we micropunctured subpleural vessels to measure microvascular pressure. At base line when alveolar pressure exceeded left atrial pressure (zone 2 conditions), 21, 38, and 41% of the total pressure drop occurred, respectively, in the arterial, microvascular, and venous segments. When we raised left atrial pressure above alveolar pressure (zone 3 conditions), the corresponding pressure drops were 30, 55, and 20% of total. The blood flow in the superficial layer of the lung averaged 15% less than the flow in the deeper layers as measured by distribution of 99mTc-albumin macroaggregates. We conclude that the intact and the isolated lung preparations in dog exhibit similar distributions of subpleural microvascular pressure.
Development of an animal model for investigating disparate myocardial effects of obesity and hypertension
Authors: Crandall D. L. , Goldstein B. M. , Lizzo F. H. , Lozito R. J. , Cervoni P.
Published: December 2017

An experimental model for investigating the disparate effects of obesity and hypertension on the heart was developed by ligation of the aorta of male Sprague-Dawley rats made obese through ad libitum feeding. Experimental obesity was associated with an increased body fat and cardiac muscle mass, yet a normotensive systemic arterial pressure. Aortic ligation produced an elevated mean arterial pressure and resting heart rate, whereas body weight was similar to that of normotensive lean control rats. Obesity and hypertension together were associated with a significantly increased percent body fat, mean arterial pressure, and left ventricular mass compared with lean controls, whereas pressure and left ventricular weight were greater than those observed in rats with only obesity or hypertension. Cardiac adaptations corrected for body weight indicated that left ventricular weight increased as a function of body weight and body fat, but hypertension produced left ventricular adaptations independent of these variables. These initial studies indicate an additional contribution of hypertension to the left ventricular adaptations of obesity, and this model could therefore be used in future investigations concerning the cardiovascular effects of the simultaneous occurrence of these separate diseases.
Regional heat flows of resting and exercising men immersed in cool water
Authors: Ferretti G. , Veicsteinas A. , Rennie D. W.
Published: December 2017

Trunk (HT), limb (HL), and whole-body (HDIR = HT + HL + Hforehead) skin-to-water heat flows were measured by heat flow transducers on nine men immersed head out in water at critical temperature (TCW = 30 ± 2 degrees C) and below [overall water temperature (TW) range = 22-32 degrees C] after up to 3 h at rest and exercise. Body heat flow was also determined indirectly (HM) from metabolic rate corrected for changes in heat stores. At rest at TCW [O2 uptake (VO2) = 0.33 ± 0.07 l/min, n = 7], HT = 52.3 + 14.2 (SD) W, HL = 56.4 ± 14.6 W, HDIR = 120 + 27 W, and HM = 111 + 29 W (significantly different from HDIR). TW markedly affected HDIR but only slightly affected HM (n = 22 experiments at TW different from TCW plus 7 experiments at TCW). During light exercise (3 MET) at TCW (VO2 = 1.06 ± 0.26 l/min, n = 9), HT = 122 ± 43 W, HL = 130 ± 27 W, HDIR = 285 ± 69 W, and HM = 260 ± 60 W. During severe exercise (7 MET) at TCW (VO2 = 2.27 ± 0.50 l/min, n = 4), HT = 226 ± 100 W, HL = 262 ± 61 W, HDIR = 517 ± 148 W, and HM = 496 ± 98 W. Lowering TW at 7-MET exercise (n = 9, plus 4 at TCW) had no effect on HDIR and HM. In conclusion, resting HL and HT are equal. At TW less than TCW at rest, HDIR greater than HM, showing that unexpectedly the shell was still cooling. During exercise, HL increases more than HT but less than expected from the heat production of the working limbs. Therefore some heat produced by the limbs is probably transported by blood to the trunk. During heavy exercise, HDIR is constant at all considered TW; apparently it is regulated by some thermally dependent mechanism, such as a progressive cutaneous vasodilation occurring as TW increases.
Convective mixing in human respiratory tract: estimates with aerosol boli
Authors: Heyder J. , Blanchard J. D. , Feldman H. A. , Brain J. D.
Published: December 2017

Convective gas mixing in the respiratory tract of 17 healthy male subjects was studied by an aerosol bolus technique. The monodisperse 1 micron di(2-ethylhexyl)sebacate droplets we used behaved as a nondiffusing gas. As the bolus was inspired to different depths and then expired, we measured the extent to which the bolus spread. We found that the deeper the bolus penetrated into the lungs, the more it became dispersed. The half-width of the expired bolus was a linear function of the volume to which the bolus penetrated at volumetric penetrations of 100-800 cm3. This suggests that convective mixing is not confined to central airways but can also occur in the lung periphery.
Genetic differences in response to pulmonary cytochrome P-450 inducers and oxygen toxicity
Authors: Mansour H. , Levacher M. , Azoulay-Dupuis E. , Moreau J. , Marquetty C. , Gougerot-Pocidalo M. A.
Published: December 2017

The effects of cytochrome P-450 inducers on O2 toxicity were studied in mice. We first examined three cytochrome P-450 inducers, which differ by their specific tissue affinity: phenobarbital sodium (PB), essentially active in the liver, and 3-methylcholanthrene (3-MC) and beta-naphthoflavone (BNF), which are also active in the lung. Both BNF and 3-MC increased the survival rate and significantly decreased pulmonary edema (pulmonary water and wet-to-dry weight ratio) in C57BL/6J mice exposed to hyperoxia (O2 greater than or equal to 95%), whereas PB had no protective effect. In the second part of this study, we compared the action of BNF in two strains of mice. In one (C57BL/6J), cytochrome P-450 can be induced by aromatic hydrocarbons, whereas in the other (DBA/2J) cytochrome P-450 is not inducible by these compounds. Protection against O2 toxicity was assessed in terms of lethality and pulmonary edema and of lung lipid peroxidation (assessed by measuring malondialdehyde). BNF only protected against O2 toxicity in the inducible strain. This protective effect of BNF on O2 toxicity in C57BL/6J mice was associated mainly with a large increase in the components of the cytochrome P-450 system (cytochrome P-450 and cytochrome b5) in the lung. The activity of pulmonary superoxide dismutase was also slightly increased, but the enhancement was not statistically significant. In contrast, in DBA/2J mice neither the components of the cytochrome P-450 system nor the activity of superoxide dismutase showed any increase.(ABSTRACT TRUNCATED AT 250 WORDS)
Linkage between brain blood flow and respiratory drive during rapid-eye-movement sleep
Authors: Parisi R. A. , Neubauer J. A. , Frank M. M. , Santiago T. V. , Edelman N. H.
Published: December 2017

The correlation between brain blood flow (BBF) and respiratory neuromotor output, as reflected by diaphragmatic electromyogram (EMG) activity (EMGdi), was studied during wakefulness, rapid-eye-movement (REM) sleep, and non-REM sleep (NREM). Compared with the awake state, mean BBF increased by 4.7% during NREM and by 32.6% during REM (P less than 0.001). Also, surges of BBF during REM occurred during periods of intense phasic activity. EMGdi [peak and peak/inspiratory time (TI)] was highly variable within REM periods but fluctuated as a reciprocal function of simultaneously measured BBf (r = -0.49, P less than 0.001). Furthermore, mean EMGdipeak decreased from NREM to REM in a manner reciprocally related to the corresponding change in BBF (r = -0.77, P = 0.015). These findings suggest that a component of the reduction of respiratory neuromotor output during REM is attributable to increased BBF with consequent relative hypocapnia in the central chemoreceptor environment.
Lung volume recruitment during high-frequency oscillation in atelectasis-prone rabbits
Authors: Byford L. J. , Finkler J. H. , Froese A. B.
Published: December 2017

In diffuse lung injury, optimal oxygenation occurs with high-frequency oscillatory ventilation (HFO-A, where A is active expiratory phase) when sustained inflations (SI) are applied periodically to recruit lung volume. Theoretically pulsed pressures may be safer and more effective than static pressures for reexpanding alveoli. We compared the increases in lung volume and arterial PO2 (PaO2) induced by 30-s increases in mean airway pressure in six New Zealand White rabbits made atelectasis prone by saline lavage plus 1 h of conventional ventilation. Pulsatile SI's (HFO-A left on during increase in mean pressure) of delta PSI = 5, 10, and 15 cmH2O and static SI's (HFO-A off during SI) of delta PSI = 5, 10, 15, and 20 cmH2O were delivered in random order. Lungs were ventilated at 15 Hz, inspired fractional concentration of O2 = 1.0, and mean airway pressure 15-20 cmH2O between test periods and deflated to functional residual capacity before each SI to standardize volume history. With both maneuvers, increases in lung volume and PaO2 induced by SI's were proportional to the magnitude of the SI (P less than 0.001) in all cases. Pulsatile SI's consistently increased lung volume and PaO2 more than static SI's having the same delta PSI (P less than 0.005) such that any given target PaO2 or change in volume (delta V) was achieved at 5 cmH2O less mean pressure with the pulsatile maneuver. Respiratory system compliance increased after both types of SI. Oxygenation and lung volume changes at 5 min were related with r = 0.58 (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Alveolar liquid pressures in newborn and adult rabbit lungs
Authors: Fike C. D. , Lai-Fook S. J. , Bland R. D.
Published: December 2017

To study the effects of lung maturation and inflation on alveolar liquid pressures, we isolated lungs from adult and newborn rabbit pups (1-11 days old). We used the micropuncture technique to measure alveolar liquid pressure at several transpulmonary pressures on lung deflation. Alveolar liquid pressure was greater than pleural pressure but less than airway pressure at all transpulmonary pressures. Alveolar liquid pressure decreased further below airway pressure with lung inflation. At high transpulmonary pressure, alveolar liquid pressure was less in newborn than in adult lungs. To study the effects of edema, we measured alveolar liquid pressures in newborn lungs with different wet-to-dry weight ratios. Alveolar liquid pressure increased with progressive edema. In addition, we compared alveolar liquid and perivenular interstitial pressures in perfused newborn lungs and found that they were similar. Thus alveolar liquid pressure can be used to estimate perivenular interstitial pressure. We conclude that the transvascular pressure gradient for fluid flux into the interstitium might increase with lung inflation and decrease with progressive edema. Furthermore, this gradient might be greater in newborn than adult lungs at high inflation pressures.
Effect of simulated altitude erythrocythemia in women on hemoglobin flow rate during exercise
Authors: Robertson R. J. , Gilcher R. , Metz K. F. , Caspersen C. J. , Allison T. G. , Abbott R. A. , Skrinar G. S. , Krause J. R. , Nixon P. A.
Published: December 2017

The effect of simulated altitude erythrocythemia on hemoglobin flow rate and maximal O2 uptake (VO2max) was determined for nine women sea-level residents. Test conditions included normoxia and normobaric hypoxia (16% O2-84% N2). Cycle tests were performed under normoxia (T1-N) and hypoxia (T1-H) at prereinfusion control and under hypoxia 48 h after a placebo infusion (T2-H) and 48 h after autologous infusion of 334 ml of erythrocytes (T3-H). Hematocrit (38.1-44.9%) and hemoglobin concentration (12.7-14.7 g.dl-1) increased from control to postreinfusion. At peak exercise, VO2max decreased from T1-N (2.40 l.min-1) to T1-H (2.15 l.min-1) then increased at T3-H (2.37 l.min-1). Maximal arterial-mixed venous O2 difference decreased from T1-N to T1-H and increased at T3-H. Cardiac output (Q), stroke volume, heart rate, and total peripheral resistance during maximal exercise were unchanged from T1-N through T3-H. Hemoglobin flow rate (Hb flow) at maximum did not change from T1-N to T1-H but increased at T3-H. When compared with submaximal values for T1-N, VO2 was unchanged at T1-H and T3-H; Q increased at T1-H and decreased at T3-H; arterial-mixed venous O2 difference decreased at T1-H and increased at T3-H; Hb flow did not change at T1-N but increased at T3-H. For young women, simulated altitude erythrocythemia increased peak Hb flow and decreased physiological altitude (227.8 m) but did not affect maximum cardiac output (Qmax).
Fatigue of the inspiratory muscle pump in humans: an isoflow approach
Authors: Clanton T. L. , Ameredes B. T.
Published: December 2017

A new method is described for measurement of inspiratory muscle endurance in humans that is based on isokinetic principles of muscle testing (i.e., measurement of maximum force during a constant velocity of shortening). Subjects inspired maximally while their lungs were inflated at a constant rate during each breath for 10 min. Inspiratory and expiratory time, flow rate, tidal volume, and end-tidal CO2 were maintained constant. In each subject, maximum inspiratory mouth pressure exponentially decayed over the first few minutes to an apparent sustainable value. Repeated tests in experienced subjects showed high reproducibility of sustainable pressure measurements. To determine the effects of flow, endurance tests were repeated in four subjects at flows of 0.75, 1.0, and 1.25 l/s, with a constant duty cycle. As flow increased, the maximum pressures that could be attained at rest and the maximum sustainable pressures decreased. At each flow, the sustainable pressure remained a constant fraction of the maximum pressure attainable at rest. We interpret the decay in mouth pressure during isoflow endurance tests to directly reflect the loss of net inspiratory muscle force available by maximum voluntary activation of the inspiratory pump.
Toluene diisocyanate-induced airway hyperreactivity in guinea pigs depleted of granulocytes
Authors: Cibulas W. , Brooks S. M. , Murlas C. G. , Miller M. L. , McKay R. T.
Published: December 2017

The influence of cyclophosphamide-induced granulocyte depletion on toluene diisocyanate (TDI)-related changes in airway reactivity and pathology was assessed in guinea pigs. Twelve cyclophosphamide-treated and 12 control animals comprising each group were studied physiologically before and 2 h after a single 10-min exposure to 3 ppm of TDI. Reactivity was determined in intact unanesthetized animals by measuring specific airway conductance before and during intravenous acetylcholine infusion. After testing, tracheal tissue for light microscopic examination was obtained from three hyperreactive guinea pigs in each exposed group and compared with tissue from treated and control animals (n = 3 each) that had not been TDI exposed. Cyclophosphamide treatment caused substantial decreases in both circulating and airway granulocyte counts. However, the incidence and degree of bronchial hyperreactivity that occurred 2 h post-TDI was similar in the untreated and treated groups. Our results indicate that TDI-induced bronchial hyperreactivity 1) occurs shortly after a brief high concentration exposure and 2) appears independent of circulating or airway granulocyte counts.
Dynamic response of peripheral chemoreflex loop to changes in end-tidal CO2
Authors: Berkenbosch A. , DeGoede J. , Ward D. S. , Olievier C. N. , VanHartevelt J.
Published: December 2017

The dynamic ventilatory response of the peripheral chemoreflex loop after isoxic step changes in end-tidal PCO2 (PETCO2) (range 5–30 Torr) was studied in 12 alpha-chloralose-urethan-anesthetized cats. The technique of artificial brain stem perfusion allowed the response to be observed in isolation from the central chemoreflex loop. The data were fitted by an exponential with time delay. During normoxia the mean time constant and time delay (with SD) were 8.6 +/- 7.3 and 3.3 +/- 0.9 s, respectively (9 cats, 56 runs). During hypoxia [arterial PO2 (PaO2) approximately 60 Torr] these values were 6.0 +/- 4.5 and 2.9 +/- 0.9 s (6 cats, 38 runs). In 17 of the 94 runs an augmented breath occurred in the first three breaths after the stepwise increase in PETCO2. For these augmented breaths, tidal volume, inspiratory time, and expiratory time were not different from the next augmented breath occurring in the same run in the steady state. Neither a rate-sensitive component nor a central neural mechanism (central afterdischarge), with the property of maintaining an increased but slowly declining respiratory activity for some minutes after cessation of the PETCO2 challenge, was found. We conclude that the description of the ventilatory response of the peripheral chemoreflex loop to step changes in PETCO2 with a single exponential and time delay is adequate.
Measurement of total respiratory impedance in calves by the forced oscillation technique
Authors: Gustin P. , Dhem A. R. , Lomba F. , Lekeux P. , Van de Woestijne K. P. , Landser F. J.
Published: December 2017

We have determined the resistance (Rrs) and the reactance (Xrs) of the total respiratory system in unsedated spontaneously breathing calves at various frequencies. A pseudorandom noise pressure wave was produced at the nostrils of the animals by means of a loudspeaker adapted to the nose by a tightly fitting mask. A Fourier analysis of the pressure in the nostrils and flow signals yielded mean Rrs and Xrs, over 16 s, at frequencies of 2–26 Hz. A good correlation was found between values of pulmonary resistances measured by the isovolume method at the respiratory frequency of animals and values obtained at a frequency of 6 Hz by use of our technique. The linearity of the respiratory system, the reproducibility of the technique, and the effects of upper airways on results have been studied. In healthy calves, Rrs increases with frequency. Mean resonant frequency is 7.5 Hz. Bronchospasm was induced in six calves by administration of intravenous organophosphates. Rrs tended to decrease with increasing frequency. Resonant frequency exceeded 26 Hz. All parameters returned to initial values after administration of atropine. In healthy calves, atropine produces a decrease in Rrs, especially at low frequencies. Values of resonant frequency are not modified.
Response of newborn lambs to CO-induced hypoxia
Authors: Bureau M. A. , Carroll J. L. , Canet E.
Published: December 2017

This study was undertaken to measure the neonate's response to CO-induced hypoxia in the first 10 days of life. CO breathing was used to induce hypoxia because CO causes tissue hypoxia with no or minimal chemoreceptor stimulation. An inspired gas mixture of 0.25 to 0.5% CO in air was used to raise the blood carboxyhemoglobin (HbCO) progressively from 0 to 60% over approximately 20 min. The study, conducted in awake conscious lambs aged 2 and 10 days, consisted in measuring the response of ventilation and the change in arterial blood gases during the rise of HbCO. The results showed that the 2- and 10-day-old lambs tolerated very high HbCO levels without an increase in minute ventilation (VE) and without metabolic acidosis. At both ages, HbCO caused no VE change until HbCO levels rose to between 45 and 50% after which the VE change was exponential in some animals but minimal in others. The VE change was brought about by a rise in tidal volume and respiratory frequency. During the period of maturation from 2 to 10 days, there was a small shift to the right in the VE-HbCO response. In the 10-day-old lambs the VE response to high HbCO was greater than that of the 2-day-olds because of the lambs' higher respiratory frequency response. Six of the 10-day-old lambs but only two of the 2-day-old lambs showed a hypoxic tachypnea to HbCO of 55–65%. None of the lambs developed periodic breathing, dysrhythmic breathing, or recurrent apneas with an HbCO level as high as 60%.(ABSTRACT TRUNCATED AT 250 WORDS)
Breath holding during intense exercise: arterial blood gases, pH, and lactate
Authors: Matheson G. O. , McKenzie D. C.
Published: December 2017

Seven healthy endurance-trained [maximal O2 uptake (VO2max) = 57.1 +/- 4.1 ml.kg-1.min-1)] female volunteers (mean age 24.4 +/- 3.6 yr) served as subjects in an experiment measuring arterial blood gases, acid-base status, and lactate changes while breath holding (BH) during intense intermittent exercise. By the use of a counterbalance design, each subject repeated five intervals of a 15-s on:30-s off treadmill run at 125% VO2max while BH and while breathing freely (NBH). Arterial blood for pH, PO2, PCO2, O2 saturation (SO2) HCO3, and lactate was sampled from a radial arterial catheter at the end of each work and rest interval and throughout recovery, and the results were analyzed using repeated-measures analysis of variance. Significant reductions in pHa (delta mean = 0.07, P less than 0.01), arterial PO2 (delta mean = 24.2 Torr, P less than 0.01), and O2 saturation (delta mean = 4.6%, P less than 0.01) and elevations in arterial PCO2 (delta mean = 8.2 Torr, P less than 0.01) and arterial HCO3 (delta mean = 1.3 meq/l, P = 0.05) were found at the end of each exercise interval in the BH condition. All of the observed changes in arterial blood gases and acid-base status induced by BH were reversed during the rest intervals. During recovery, significantly (P less than 0.025) greater levels of arterial lactate were found in the BH condition.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of nitroprusside on lung mechanics and hemodynamics after endotoxemia in awake sheep
Authors: Wright P. , Ishihara Y. , Bernard G. R.
Published: December 2017

We examined the effects of intravenous sodium nitroprusside (NP) infusion on pulmonary arterial pressure (Ppa), pulmonary vascular resistance (PVR), dynamic compliance (Cdyn), resistance to airflow across the lungs (RL), and alveolar-arterial O2 pressure gradient (PAO2-PaO2) (room air) after endotoxemia in awake sheep. NP infused 2.5 h after endotoxin administration immediately reduced mean Ppa from 30 +/- 3 to 17 +/- 3 (SE) cmH2O, PVR from 6.3 +/- 0.7 to 4.8 +/- 0.5 cmH2O.l-1.min, and RL from 340 +/- 48 of base line to 205 +/- 73% and increased Cdyn from 54 +/- 5 of base line to 80 +/- 14% without affecting PAO2--PaO2. Ppa and lung mechanics returned immediately to preinfusion levels when NP was stopped. In vitro experiments with NP showed a dose-dependent relaxation of preconstricted pulmonary artery and vein, carbachol-preconstricted sheep tracheal strips, and bronchial rings. We conclude that NP reverses pulmonary hypertension and lung mechanics abnormalities after endotoxin and that this is due to effects of NP on airway and vascular smooth muscle. The return of these abnormalities after NP cessation suggests the continued presence of vascular and airway-constricting factors late after endotoxin. The lack of effect of NP on blood oxygenation suggests that deleterious effects on hypoxic vasoconstriction are offset by improved lung mechanics.