bluuebunny/crossref_metadata_2025 huggingface dataset:
Pulmonary blood flow and tissue volume: model analysis of rebreathing estimation methods
Authors: Burma G. M. , Saidel G. M.
Published: December 2017

As the basis for comparing rebreathing methods of estimating pulmonary blood flow (Q) and tissue-capillary volume (Vtc), we use a dynamic mass-balance model for gas species having different physicochemical properties (e.g., He, CO, C2H2). The model accounts for the effects of ventilation and perfusion inhomogeneities, breathing pattern variation, lung and rebreathing-bag volumes, and recirculation. Also, we examine the variability of the estimates caused by random error. In addition to analyzing two well-known methods, we show how an appropriate synthesis of these methods can lead to improved estimates.
Mechanisms of histamine-induced contraction of canine airway smooth muscle
Authors: Shore S. , Irvin C. G. , Shenkier T. , Martin J. G.
Published: December 2017

We studied the effects of atropine (10(-10) to 10(-6) M), tetrodotoxin (TTX) (10(-6) g/ml), and neostigmine (10(-7) M) on the histamine dose-response curve of canine tracheal smooth muscle (TSM) in vitro. Pretreatment with atropine or TTX reduced base-line tension in some TSM samples, whereas neostigmine invariably caused contraction of TSM. All concentrations of atropine reduced the maximum isometric tension produced by histamine (Tmax). With 10(-6), 10(-8), and 10(-10) M atropine, Tmax was 57, 74, and 88%, respectively, of its value in paired control samples. Atropine, 10(-9) to 10(-6) M, increased the concentration of histamine which produced 20% of Tmax, whereas 10(-6) M also increased the concentration required to produce 50% of Tmax. TTX reduced tension produced by low concentrations of histamine but had no effect at higher concentrations. Neostigmine shifted the histamine dose-response curve and caused greater tension for any given histamine concentration; Tmax increased by 30% (P less than 0.05). Our data are consistent with spontaneous release of acetylcholine from cholinergic nerves in the airway tissue and suggest that histamine either accelerates this release or interacts supra-additively with the acetylcholine at the smooth muscle.
Effects of pH on maximal power output and fatigue during short-term dynamic exercise
Authors: McCartney N. , Heigenhauser G. J. , Jones N. L.
Published: December 2017

Six healthy subjects performed four exercise studies in random order on separate days: a control study, metabolic acidosis induced by ammonium chloride, metabolic alkalosis induced by sodium bicarbonate, and respiratory acidosis induced by 5% CO2 inhalation. The subjects exerted maximal force on the pedals of a constant-velocity cycle ergometer at 100 rpm for 30 s; torque was measured and power calculated. Arterialized venous blood was sampled, and plasma lactate concentrations was measured immediately after and at 2-min intervals for 10 min following exercise. Although maximal peak power and total work, for the 30-s test, were lower in the two acidosis conditions, this effect was not statistically significant. Plasma lactate 30-s postexercise was lower in metabolic acidosis (2.8 +/- 1.6 mmol X 1(-1) (mean +/- SD) and respiratory acidosis (1.5 +/- 0.8 mmol X 1(-1) than in placebo conditions (5.9 +/- 3.3 mmol X 1(-1) and metabolic alkalosis 7.8 +/- 4.2 mmol X 1(-1). These differences were maintained but lessened during 10 min of recovery. In contrast to previous studies, which showed a marked reduction in endurance time during sustained heavy exercise, reductions in blood pH are associated with only small reductions in the total work performed in 30 s of maximal exercise. A delayed and smaller accumulation of lactate in plasma was observed following exercise during acidosis.
Carbohydrate feeding during prolonged strenuous exercise can delay fatigue
Authors: Coyle E. F. , Hagberg J. M. , Hurley B. F. , Martin W. H. , Ehsani A. A. , Holloszy J. O.
Published: December 2017

This study was undertaken to determine whether carbohydrate feeding during exercise can delay the development of fatigue. Ten trained cyclists performed two bicycle ergometer exercise tests 1 wk apart. The initial work rate required 74 +/- 2% of maximum O2 consumption (VO2 max) (range 70-79% of VO2 max). The point of fatigue was defined as the time at which the exercise intensity the subjects could maintain decreased below their initial work rate by 10% of VO2 max. During one exercise test the subjects were fed a glucose polymer solution beginning 20 min after the onset of exercise; during the other they were given a placebo. Blood glucose concentration was 20-40% higher during the exercise after carbohydrate ingestion than during the exercise without carbohydrate feeding. The exercise-induced decrease in plasma insulin was prevented by carbohydrate feeding. The respiratory exchange ratio was unchanged by the glucose feeding. Fatigue was postponed by carbohydrate feeding in 7 of the 10 subjects. This effect appeared to be mediated by prevention of hypoglycemia in only two subjects. The exercise time to fatigue for the 10 subjects averaged 134 +/- 6 min (mean +/- SE) without and 157 +/- 5 min with carbohydrate feeding (P less than 0.01).
Two-sidearm tracheal cannula for respiratory airflow measurements in small animals
Authors: Mortola J. P. , Noworaj A.
Published: December 2017

We have investigated the possibility of using a two-sidearm tracheal cannula for measurements of respiratory airflow. Measurements of mean flow and tidal volume using four such cannulas (0.7, 1.5, 1.8, and 2.5 mm ID) are described. They have a linear response up to flows of 6, 10, 12, and 28 ml X s-1, respectively, that correspond to 100 ml X s-1 X kg-1 or more, depending on the body size of the animals (15-350 g) in which they could be used. These characteristics, coupled with small volume and flow resistance, make the use of these cannulas as pneumotachographs a suitable and very practical way of measuring mean airflow and tidal volume in anesthetized small animals, ranging in size from newborn rats to newborn puppies.
Cardiac output and skin blood flow in lean and obese individuals during exercise in the heat
Authors: Vroman N. B. , Buskirk E. R. , Hodgson J. L.
Published: December 2017

Five obese (% body fat greater than or equal to 27%) and five relatively lean (% body fat less than 20%) men performed upright exercise on a cycle ergometer at intensities of 30, 50, and 70% of their maximal aerobic power [VO2max (ml X kg fat-free wt-1 X min-1)] in both a thermoneutral [dry bulb temperature (Tdb) = 22 degrees C, wet bulb temperature (Twb) = 14 degrees C] and a hot (Tdb = 38 degrees C, Twb = 20 degrees C) ambient environment. Cardiac output (Q) was measured by CO2 rebreathing and forearm blood flow (FBF) was measured by venous occlusion plethysmography. Esophageal temperature (Tes) was measured by a thermocouple placed in the esophagus at approximately heart level, and mean skin temperature (Tsk) was calculated from the average of thermocouple readings from six skin sites. When the exercise intensity was normalized for metabolic body mass by dividing by fat-free weight, Q was similar between lean and obese at all exercise intensities and in both ambient environments. No differences between the two groups were found in Tes and Tsk under all conditions. The obese had significantly lower FBF compared with the lean during the higher exercise intensities in the hot ambient environment. In both ambient environments, the slope of the FBF-Tes relationship was significantly less in the obese group. It was concluded that body composition may alter the balance between the two opposing sets of cutaneous vascular reflexes (baroreceptor-induced vasoconstriction and thermoregulatory vasodilation) that regulate the competition for blood flow between the skin and working muscle during exercise in the heat.
Effect of granulocyte depletion on altered lung mechanics after endotoxemia in sheep
Authors: Hinson J. M. , Hutchison A. A. , Ogletree M. L. , Brigham K. L. , Snapper J. R.
Published: December 2017

To examine the role of circulating granulocytes in the airway changes caused by endotoxemia, we measured the response of chronically instrumented unanesthetized sheep to endotoxemia before and after granulocyte depletion with hydroxyurea. Granulocyte depletion did not affect the increases in mean pulmonary arterial pressure caused by endotoxin [peak pressure 59 +/- 8 cmH2O +/- (SE) control, 51 +/- 8 cmH2O granulocyte depleted]. However, the early (30-60 min after endotoxin) airway response to endotoxemia was markedly attenuated. Without granulocyte depletion, endotoxin caused dynamic compliance (Cdyn) to decrease to 41 +/- 10% of the base-line value and total lung resistance (RL) to increase to 283 +/- 61% of base line. When animals were granulocyte depleted, endotoxin decreased Cdyn to 69 +/- 6% (P less than 0.05) of base line and increased RL to 141 +/- 20% of base line (P less than 0.05). Granulocyte depletion also attenuated the effect of endotoxin on arterial oxygenation. During the maximum airway response to endotoxin, the alveolar-to-arterial oxygen gradient was 47 +/- 5 Torr in control studies and 32 +/- 2 Torr in granulocyte depleted studies (P less than 0.05). We conclude that interaction of granulocytes with the lung contributes to the changes in lung mechanics observed following endotoxemia and that the early pulmonary hypertension and the early alterations in lung mechanics caused by endotoxemia are caused by separate processes.
Canine blood volume and cardiovascular function during hyperthermia
Authors: Miki K. , Morimoto T. , Nose H. , Itoh T. , Yamada S.
Published: December 2017

The effect of acute hyperthermia on hemodynamic functions and blood volume regulation was examined on eight splenectomized dogs. Elevation of core body temperature by 2 degrees C over 90 min caused significant increase in cardiac output (11.2 +/- 12.5 ml X min-1 X kg-1 or about 10%) and significant decrease in total peripheral resistance (TPR; -1.3 +/- 1.0 mmHg X s X ml-1 or about 20%), whereas blood volume (BV), plasma oncotic pressure, and intravascular protein mass remained unchanged. Thus the raised core temperature caused peripheral vasodilation with decreased TPR and compensatory increase in cardiac output. Because BV remained unchanged during warming, mobilization of extravascular fluid did not occur; only the redistribution of blood to the vasodilated cutaneous circulation took place. To assess the effects of heat stress on transvascular fluid equilibrium, Ringer solution (10.7 ml X kg-1 X 10 min-1) was infused under normothermic and hyperthermic conditions. The volume of fluid retained within the intravascular space under equilibrium state was 33.5% in hyperthermia and 9.4% in normothermia. In hyperthermia, the transvascular fluid shift and urinary output were decreased both during and after infusion. The role of preferential fluid retention within the intravascular space observed during hyperthermia was discussed in relation to the mechanism to maintain cardiovascular function and BV under heat stress.
Effect of exercise on left ventricular diastolic filling in athletes and nonathletes
Authors: Matsuda M. , Sugishita Y. , Koseki S. , Ito I. , Akatsuka T. , Takamatsu K.
Published: December 2017

To evaluate the effect of exercise on left ventricular diastolic filling, the following were measured at rest and during exercise in 14 control subjects and 15 athletes, using digitized M-mode echocardiography: the peak early diastolic lengthening rate of the left ventricular dimension and the filling volume and the filling fraction during the first 0.10 s of diastole. During ergometer exercise performed at a level that increased the heart rate to 100 beats/min, there were significant increases in the peak normalized lengthening rate of the left ventricular dimension (control subjects, 4.2 +/- 1.3 vs. 6.1 +/- 1.1 s-1, mean +/- SD, P less than 0.001; athletes, 5.3 +/- 0.9 vs. 7.4 +/- 1.1 s-1, P less than 0.001), filling volume (control subjects, 15 +/- 12 vs. 33 +/- 10 ml, P less than 0.001; athletes, 21 +/- 12 vs. 63 +/- 18 ml, P less than 0.001), and filling fraction (control subjects, 21 +/- 14 vs. 42 +/- 17%, P less than 0.005; athletes, 21 +/- 13 vs. 54 +/- 12%, P less than 0.01). The peak lengthening rate of the left ventricular dimension, the filling volume, and the filling fraction were significantly greater in athletes than in control subjects during exercise (P less than 0.005, P less than 0.001, and P less than 0.05, respectively). Augmented early diastolic filling may be a mechanism to provide adequate filling for the ventricle at high heart rates produced by exercise, especially in athletes.
Influence of chest wall distortion on esophageal pressure
Authors: LeSouef P. N. , Lopes J. M. , England S. J. , Bryan M. H. , Bryan A. C.
Published: December 2017

The caudocephalad profile of esophageal pressure swings was studied in 10 preterm and 5 full-term infants, and the effect of chest wall distortion on esophageal pressure swings was analyzed in 12 preterm infants. Esophageal pressure was measured with a fluid-filled catheter, tidal volume with a pneumotachograph, mouth pressure with a face mask and pressure transducer, and rib cage and abdominal motion with magnetometers. In preterm infants the profile of esophageal pressure swings fell very steeply in the caudocephalad direction. In full-term infants it was flat during quiet sleep and steep during rapid-eye-movement sleep. When breaths, standardized for pleural pressure, were compared between a period with maximal and a period with minimal chest wall distortion, esophageal pressure swings for both spontaneous and occluded breaths were higher in the former period. We conclude that the complaint preterm rib cage results in an uneven distribution of pleural pressure and that this distribution varies with changes in chest wall distortion. Esophageal pressure measurements are therefore an unreliable estimate of mean pleural pressure in the preterm infant and can be unreliable in the term infant.
Effect of chest wall distortion on occlusion pressure and the preterm diaphragm
Authors: LeSouef P. N. , Lopes J. M. , England S. J. , Bryan M. H. , Bryan A. C.
Published: December 2017

We studied the effect of chest wall distortion (CWD) on transdiaphragmatic pressure (Pdi) and/or mouth pressure during end-expiratory airway occlusions in seven preterm infants. We measured mouth occlusion pressure (Pmo) with a face mask and pressure transducer, gastric pressure (Pga) with a fluid-filled catheter, diaphragmatic electromyogram (Edi) using surface electrodes, and rib cage and abdominal motion using magnetometers. We reasoned that Pdi = Pmo - Pga on airway occlusion. Periods with maximal and periods with minimal CWD were compared. We found that 1) when CWD was minimal, an increase in Edi produced an increase in Pmo and Pdi in all infants; when CWD was greatest, large increases in Edi produced no increase in Pmo or Pdi in four infants; 2) when breaths with the same Pmo or Pdi from each period in each infant were compared, those from the period with greatest CWD had an increased Edi (mean increase 76%, P less than 0.005, and 144%, P less than 0.01, for Pmo and Pdi, respectively). We conclude that in preterm infants, Pmo can be a poor indicator of respiratory drive, and CWD markedly limits the effectiveness of the diaphragm as a force generator.
Pulmonary metabolic function in the awake lamb: effect of development and hypoxia
Authors: Pitt B. R. , Lister G.
Published: December 2017

The effect of postnatal development and acute alveolar hypoxia on pulmonary metabolic function was studied in conscious newborn lambs. Measurements of the ability of the lungs of these animals to metabolize [3H]benzoyl-L-phenyl-alanyl-L-alanyl-L-proline ([3H]BPAP; a synthetic substrate for angiotensin-converting enzyme, ACE) and to remove 5-hydroxy-[14C]tryptamine (5-[14C]HT) were made by modified indicator-dilution techniques during normoxic and hypoxic (fraction of inspired O2 = 0.10) conditions at 1 day, 1 wk, and 1 mo of age. Six additional sheep (8-23 wk old) were studied acutely as “adult” controls. BPAP metabolism in the 1-day-old group was 48 +/- 3% and increased slowly to 57 +/- 1% (P less than 0.05) at 1 mo of age and to 79 +/- 3% (P less than 0.01) by 23 wk of age. Pulmonary 5-[14C]HT removal was adultlike at birth (69 +/- 2%). Alveolar hypoxia significantly decreased BPAP only in the 1-day-old group (41 +/- 3%; P less than 0.05) and had no significant effect on 5-[14C]HT removal over the range of ages studied. These data demonstrate a selective and gradual postnatal development of pulmonary ACE which could be due to alterations in either the affinity or maximal capacity of pulmonary ACE, or increased endothelial cell surface area secondary to rapid growth of small blood vessels in this period. Alveolar hypoxia does not appear to closely regulate either ACE activity or 5-HT removal in conscious lambs greater than 1 day old when trace amounts of substrate are used.
Factors determining the frequency content of the electromyogram
Authors: Kranz H. , Williams A. M. , Cassell J. , Caddy D. J. , Silberstein R. B.
Published: December 2017

The contribution of central and peripheral factors to the frequency content of the electromyogram was examined in 10 subjects performing maximal 45-s contractions of thenar muscles. The median frequencies (Fm) of surface-recorded electromyograms and compound action potentials were similar early (P greater than 0.6) and late (P greater than 0.5) in the contractions. There was a mean decrease in the Fm during contraction of 39% for electromyograms and 35% for compound potentials (P greater than 0.1). The Fm of electromyograms increased 11% (P less than 0.02) in only the 1st s of contraction as force was raised from 25 to 100% of maximum. Only one of five subjects showed evidence of increasing synchronization of motor unit discharge during contraction. There was no evidence that delay or dispersion of action potential propagation in terminal nerve fibers or at the neuromuscular junction had a significant effect on frequency content. The findings indicated that the spectral content of muscle electrical activity, and its shift during contraction, primarily reflects intrinsic muscle properties.
Effect of prolonged exercise at altitude on the renin-aldosterone system
Authors: Milledge J. S. , Catley D. M. , Williams E. S. , Withey W. R. , Minty B. D.
Published: December 2017

The combined effect of exercise and altitude on the renin-aldosterone system was studied in six male subjects on a fixed diet. After 4 control days at rest and at low altitude, subjects ascended to 3,100 m and took about 7 h exercise daily for 5 days. There followed a 4-day recovery period at low altitude. Daily blood samples were taken for estimation of plasma renin activity (PRA), plasma aldosterone concentration (PAC), and angiotensin converting-enzyme (ACE) activity. Results showed a maximal rise in PRA and PAC with exercise at altitude maximal on the first 2 days. ACE activity fell by 23% at altitude. Compared with similar exercise at sea level, the rise in PAC was comparable but the rise in PRA was four times greater, indicating a marked decrease in PAC response to PRA. It is suggested that this loss of sensitivity of PAC to PRA is mediated by the measured reduction in ACE activity.
Independent brain stem sites for ventilatory neurogenesis
Authors: St John W. M.
Published: December 2017

The purpose was to determine if independent ventilatory rhythms could be generated in each half of completely separated brain stems. In decerebrate, cerebellectomized, vagotomized, paralyzed, and ventilated cats, activities of phrenic, recurrent laryngeal (RLN), and/or hypoglossal nerves were monitored. Midsaggital brain stem divisions were performed by sections and lesions. Eupnea continued following divisions of mesencephalon and pons. Hypoglossal and phrenic activities were eliminated after sections approximating the obex. In most preparations, RLNs discharged with independent rhythms after completion of midsagittal brain stem section and a C1 transection. Independent rhythms were also obtained from each half of medulla following transections at the pontomedullary junction and at C1, and midsagittal medullary divisions. In other animals with transections between pons and medulla and at C1, synchronized RLN and hypoglossal activities persisted after sagittal medullary divisions, 2.0 mm lateral to midline contralaterally. Data demonstrate that there is more than one potential brain stem site for ventilatory neurogenesis. It is hypothesized that there are many such sites, possibly having pacemaker cells, in pons and medulla.
Effects of acute moderate-intensity exercise on carnitine metabolism in men and women
Authors: Lennon D. L. , Stratman F. W. , Shrago E. , Nagle F. J. , Madden M. , Hanson P. , Carter A. L.
Published: December 2017

The purpose of this investigation was to describe the dynamics of carnitine metabolism during an acute episode of exercise. Twenty-eight subjects (14 male; 14 female) exercised for 40 min on a bicycle ergometer at 55% of their maximal aerobic capacities. Blood samples were obtained at rest, 10, 20, 30, and 40 min of exercise, and 15-min postexercise. Muscle biopsies of the vastus lateralis were performed before and after exercise. Results demonstrated that the percent of acylated plasma carnitine increased significantly (P less than 0.05) across all subjects from 17.3% at rest to 22.3% by 40 min of exercise and continued to increase to 22.8% 15-min postexercise. Total muscle carnitine levels fell significantly (P less than 0.001) across all subjects from 4.21 (1.27) (means +/- SD) mumol/g wet weight at rest to 3.29 (1.27) mumol/g wet weight after exercise. Well-trained males and females had almost identical levels of muscle carnitine [4.35(1.86) and 4.34 (0.64) mumol/g wet weight, respectively]. These levels were somewhat higher but not significantly higher than their moderately trained counterparts [3.86(1.34) and 4.28(1.18) males and females, respectively]. Carnitine palmitoyl transferase (E.C. 2.3.1.21) activity also declined significantly (P less than 0.05) across all subjects after exercise. This study is the first to demonstrate a potential loss of acylated carnitine forms from muscle to plasma during acute exercise, possibly reflecting an increase in carnitine turnover. Alterations in carnitine status may represent another metabolic adaptation to chronic exercise training.
Phosphatidylglycerol-deficient lung surfactant has normal properties
Authors: Beppu O. S. , Clements J. A. , Goerke J.
Published: December 2017

We have investigated the effects of substituting phosphatidylinositol (PI) for phosphatidylglycerol (PG) on the functional properties of rabbit lung surfactant. We gave oral 10% glucose solution for 3 days to 11 rabbits and 10% inositol to 12 others. Lung lavage surfactant phospholipids were normal in both groups, except that PG was low and PI was high in the inositol group. Fatty acyl group distributions did not differ, except for a slight decrease of oleic acid in the inositol group. Electron microscopic examination showed normal surfactant structure in both. The time course of surfactant adsorption to an air-water interface was similar in both groups. Minimum surface tension after film compression was 4.0 +/- 0.8 mN . m-1 in the glucose group and 2.9 +/- 1.3 mN . m-1 in the inositol group (mean +/- SE). Surface potential-surface pressure isotherms were identical to within 12 mV. Arterial blood gases breathing air and 100% O2 were the same in both groups, as were pressure-volume curves of excised lungs, with both air and saline filling. The results suggest that, if acidic phospholipids are necessary for maintaining normal surfactant structure and surface properties, normal pressure-volume relationships, and normal gas exchange, then PI may substitute for PG.
Effects of exercise and lack of exercise on glucose tolerance and insulin sensitivity
Authors: Heath G. W. , Gavin J. R. , Hinderliter J. M. , Hagberg J. M. , Bloomfield S. A. , Holloszy J. O.
Published: December 2017

Physically trained individuals have a markedly blunted insulin response to a glucose load and yet have normal glucose tolerance. This phenomenon has generally been ascribed to long-term adaptations to training which correlate with maximal oxygen uptake (VO2max) and reduced adiposity. Our study was undertaken to test the hypothesis that residual effects of the last bouts of exercise play an important role in this phenomenon. Eight well-trained subjects stopped training for 10 days. There were no significant changes in VO2max (58.6 +/- 2.2 vs. 57.6 +/- 2.1 ml/kg), estimated percent body fat (12.5 +/- 0.7 vs. 12.5 +/- 0.8%), or body weight. The maximum rise in plasma insulin concentration in response to a 100-g oral glucose load was 100% higher after 10 days without exercise than when the subjects were exercising regularly. Despite the increased insulin levels, blood glucose concentrations were higher after 10 days without exercise. Insulin binding to monocytes also decreased with physical inactivity. One bout of exercise after 11 days without exercise returned insulin binding and the insulin and glucose responses to an oral 100-g glucose load almost to the initial “trained” value. These results support our hypothesis.
A model of inspiratory muscle mechanics
Authors: Macklem P. T. , Macklem D. M. , De Troyer A.
Published: December 2017

We have previously shown that the costal and crural parts of the diaphragm have different actions on the rib cage (RC) and that the tension developed in one part is not transmitted perfectly to the other. Thus the diaphragm can be modeled pneumatically or electrically as two generators or pumps in series between the lung and abdomen. As such, the force developed by diaphragmatic contraction is the sum of the forces developed in each part, whereas the volume displaced is the same for each part and equal to the total volume displaced. The costal part of the diaphragm is in series with the intercostal and accessory (IA) muscles between the lung and RC, whereas the crural part is in parallel. The volume displaced by simultaneous contraction of the crural part and IA is the sum of volumes displaced by each part. The action of pleural and abdominal pressure [acting through the area of apposition (Aap) of the diaphragm to RC] can be modelled as a summing junction between IA and RC. With hyperinflation the costal part acts more and more in parallel with both IA and the crural part, whereas Aap diminishes, so that the ability to develop large forces decreases independently of the muscles' force-length relationships. The model also predicts that the factors determining the length of the costal and crural parts are different. Finally, the parallel and serial arrangement of the inspiratory musculature allows for increases in maximum power, maximum force, and maximum velocity by appropriate recruitment of the various muscle groups.
Low exercise pulmonary resistance is not dependent on vasodilator prostaglandins
Authors: Lindenfeld J. , Reeves J. T. , Horwitz L. D.
Published: December 2017

In resting conscious dogs, administration of cyclooxygenase inhibitors results in modest increases in pulmonary arterial pressure and pulmonary vascular resistance, suggesting that vasodilator prostaglandins play a role in maintaining the low vascular resistance in the pulmonary bed. To assess the role of these vasodilator prostaglandins on pulmonary vascular resistance during exercise, we studied seven mongrel dogs at rest and during exercise before and after intravenous meclofenamate (5 mg/kg). Following meclofenamate, pulmonary vascular resistance rose both at rest (250 24 vs. 300 +/- 27 dyn . s . cm-5, P less than 0.01) and with exercise (190 +/- 9 vs. 210 +/- 12 dyn . s . cm-5, P less than 0.05). Systemic vascular resistance rose slightly following meclofenamate both at rest and during exercise. There were no changes in cardiac output. The effects of cyclooxygenase inhibition, although significant, were less during exercise than at rest. This suggests that the normal fall in pulmonary vascular resistance during exercise depends largely on factors other than vasodilator prostaglandins.
A programmable electrically braked ergometer
Authors: Giezendanner D. , Di Prampero P. E. , Cerretelli P.
Published: December 2017

Research protocols require that the actual braking power (Wb) of electrically braked ergometers (EBE) is precisely set at the chosen power level, stable, and universally programmable. No commercially available EBEs appear to meet jointly the above conditions. In fact, EBE settings were found to deviate up to 25% from the reference level (WR), their Wb to drop as a result of increased temperature as much as 30% within 1 h of continuous operation, and the programming features to be limited and rigid. To overcome the above pitfalls a procedure for building or improving EBEs is presented whereby 1) the stator of the brake used as a dynamometer is mounted on ball bearings, the torque being transmitted to a strain gauge; 2) the number of revolutions of the rotor is measured on a cogwheel by a proximity detector and an impulse counter; and 3) the torque and impulse number signals are fed into a low-priced microcomputer controlling the brake's power supply. The device has proved to be satisfactory in following any preprogrammed exercise-forcing functions. In the range approximately 10-500 W, Wb = WR +/- 1%.
Correcting for the dynamic response of a respiratory mass spectrometer
Authors: Bates J. H. , Prisk G. K. , Tanner T. E. , McKinnon A. E.
Published: December 2017

Mass spectrometers produce distorted measurements of gas concentrations because of the time delays and rise times inherent in their responses. Three techniques for numerically correcting such distortion were applied to the acetylene step responses of a Perkin-Elmer MGA1100 mass spectrometer and to simulated data. The techniques investigated were 1) a simple time-delay correction, 2) an exponential model method that assumes a biexponential form for the peak of the impulse response, and 3) a Fourier transform method of deconvolution known as Wiener filtering. The time-delay correction produced an order of magnitude reduction in measurement error. The exponential model method improved on the time-delay correction, and the Wiener filter gave the most accurate corrections in all cases examined.
A versatile hydraulically operated respiratory servo system for ventilation and lung function testing
Authors: Meyer M. , Slama H.
Published: December 2017

A description is given of the design and performance of a microcomputer-controlled respiratory servo system that incorporates the characteristics of a mechanical ventilator and also allows the performance of a multitude of test procedures required for assessment of pulmonary function in paralyzed animals. The device consists of a hydraulically operated cylinder-piston assembly and solenoid valves that direct inspiratory and expiratory gas flow and also enable switching to different test gas sources. The system operates as a volume-flow-preset ventilator but may be switched to other operational cycling modes. Gas flow rates may be constant or variable. The system operates as an assister-controller and, combined with a gas analyzer, can function as a “demand” ventilator allowing for set-point control of end-tidal PCO2 and PO2. Complex breathing maneuvers for a variety of single- and multiple-breath lung function tests are automatically performed. Because of the flexibility in selection and timing of respiratory parameters, the system is particularly suitable for respiratory gas studies.
Pulmonary gas exchange on the summit of Mount Everest
Authors: West J. B. , Hackett P. H. , Maret K. H. , Milledge J. S. , Peters R. M. , Pizzo C. J. , Winslow R. M.
Published: December 2017

Pulmonary gas exchange was studied on members of the American Medical Research Expedition to Everest at altitudes of 8,050 m (barometric pressure 284 Torr), 8,400 m (267 Torr) and 8,848 m (summit of Mt. Everest, 253 Torr). Thirty-four valid alveolar gas samples were taken using a special automatic sampler including 4 samples on the summit. Venous blood was collected from two subjects at an altitude of 8,050 m on the morning after their successful summit climb. Alveolar CO2 partial pressure (PCO2) fell approximately linearly with decreasing barometric pressure to a value of 7.5 Torr on the summit. For a respiratory exchange ratio of 0.85, this gave an alveolar O2 partial pressure (PO2) of 35 Torr. In two subjects who reached the summit, the mean base excess at 8,050 m was -7.2 meq/l, and assuming the same value on the previous day, the arterial pH on the summit was over 7.7. Arterial PO2 was calculated from changes along the pulmonary capillary to be 28 Torr. In spite of the severe arterial hypoxemia, high pH, and extremely low PCO2, subjects on the summit were able to perform simple tasks. The results allow us to construct for the first time an integrated picture of human gas exchange at the highest point on earth.
Maximal exercise at extreme altitudes on Mount Everest
Authors: West J. B. , Boyer S. J. , Graber D. J. , Hackett P. H. , Maret K. H. , Milledge J. S. , Peters R. M. , Pizzo C. J. , Samaja M. , Sarnquist F. H. , et al.
Published: December 2017

Maximal exercise at extreme altitudes was studied during the course of the American Medical Research Expedition to Everest. Measurements were carried out at sea level [inspired O2 partial pressure (PO2) 147 Torr], 6,300 m during air breathing (inspired PO2 64 Torr), 6,300 m during 16% O2 breathing (inspired PO2 49 Torr), and 6,300 m during 14% O2 breathing (inspired PO2 43 Torr). The last PO2 is equivalent to that on the summit of Mt. Everest. All the 6,300 m studies were carried out in a warm well-equipped laboratory on well-acclimatized subjects. Maximal O2 uptake fell dramatically as the inspired PO2 was reduced to very low levels. However, two subjects were able to reach an O2 uptake of 1 l/min at the lowest inspired PO2. Arterial O2 saturations fell markedly and alveolar-arterial PO2 differences increased as the work rate was raised at high altitude, indicating diffusion limitation of O2 transfer. Maximal exercise ventilations exceeded 200 l/min at 6,300 m during air breathing but fell considerably at the lowest values of inspired PO2. Alveolar CO2 partial pressure was reduced to 7-8 Torr in one subject at the lowest inspired PO2, and the same value was obtained from alveolar gas samples taken by him at rest on the summit. The results help to explain how man can reach the highest point on earth while breathing ambient air.
Reversal of arterial-to-expired CO2 partial pressure differences during rebreathing in goats
Authors: Steinbrook R. A. , Fencl V. , Gabel R. A. , Leith D. E. , Weinberger S. E.
Published: December 2017

Whether CO2 partial pressure (PCO2) in expired gas may exceed that in arterial blood has been controversial. We measured arterial PCO2 (Paco2) and end-tidal PCO2 (PETco2) in four awake goats during air breathing and during hyperoxic CO2 rebreathing in various conditions of acid-base balance. During air breathing, Paco2 was slightly higher than PETco2; i.e., the mean (+/- SE) difference, Paco2 - PETco2, was positive by + 2.36 +/- 0.53 Torr (P less than 0.001). In contrast, during CO2 rebreathing with the same techniques of measurement, this difference was always negative (mean +/- SE = -11.63 +/- 0.22 Torr, P less than 0.001), and it widened as Paco2 increased with rebreathing. Magnitude of the negative difference during rebreathing was too great to be accounted for by incorrect assumptions or measurement error, even if reasonable contributions from all known sources of error were concurrently invoked. We conclude that during hyperoxic CO2 rebreathing in goats, PETco2 exceeds Paco2.
Responses of the lung periphery to 1.0 ppm ozone
Authors: Gertner A. , Bromberger-Barnea B. , Dannenberg A. M. , Traystman R. , Menkes H.
Published: December 2017

We studied responses of the lung periphery to short-term exposures of 1.0 ppm ozone (O3). A fiber-optic bronchoscope was wedged in a segmental airway of anesthetized male mongrel dogs and was used to deliver O3 to a small portion of lung. Measurements of resistance through the collateral system (Rcs) were used to monitor responses to O3. During a 30-min exposure to O3, Rcs increased within 2 min (early phase) and then continued to increase throughout the exposure. Bilateral cervical vagotomy or pretreatment with atropine prevented or reduced the response measured at 2 min but not the later increase in Rcs. The later increase was reduced with chlorpheniramine. The administration of indomethacin intravenously and as an aerosol did not alter the response. These results indicate that the early phase of the response to 1.0 ppm ozone in the lung periphery is mediated through the parasympathetic system, and the later phase of the response is related in part to histamine release. We found no evidence that metabolites of the cyclooxygenase pathway played a role in these responses. Furthermore, unlike responses to 0.1 ppm, responses to 1.0 ppm O3 are not characterized by the development of adaptation or tolerance.
Respiratory-related hypoglossal nerve activity: influence of anesthetics
Authors: Hwang J. C. , St John W. M. , Bartlett D.
Published: December 2017

In decerebrate, vagotomized, paralyzed, and ventilated cats, phrenic and respiratory-related hypoglossal discharges were evident at normocapnic normoxia or hyperoxia. Both increased progressively in hypercapnia or hypoxia. With increasing drive, onset of inspiratory hypoglossal activity began earlier relative to phrenic onset; an early expiratory hypoglossal burst was also observed. Following subanesthetic doses of chloralose, halothane, ketamine, or pentobarbital, hypoglossal activity was depressed much more than phrenic discharge. In moderate hypercapnia or hypoxia, phrenic activity increased more than hypoglossal, whereas, at high drive, the latter rose more sharply in some cats. Electromyograms of the diaphragm and genioglossus were recorded in intact awake cats to determine if their responses and those of decerebrates are comparable. Respiratory-related genioglossal discharge was evident in normocapnia. We conclude that anesthesia suppresses hypoglossal motor activities much more than those of the bulbospinal-phrenic system. Data for decerebrate cats and unanesthetized cats or humans provide no evidence of a differential distribution of chemoreceptor afferents on hypoglossal and bulbospinal-phrenic neurons, as suggested by results in anesthetized animals.
Changes in vascular responsiveness following chronic exposure to cold in the rat
Authors: Bryar B. A. , Fregly M. J. , Field F. P.
Published: December 2017

The responsiveness of smooth muscle from rings of aortic tissue of cold-acclimated (CA, 6 degrees C, 5-15 wk) rats to both alpha- and beta-adrenergic agonists and KCl was tested and compared with that of warm-adapted (25 degrees C) controls. alpha-Adrenergic stimulation, induced by low doses (10(-8)-10(-7) M) of phenylephrine and norepinephrine in the presence and absence of the beta-adrenergic antagonist, propranolol, resulted in the development of less active tension by aortic smooth muscle from CA rats than from controls. Similar results were observed with the weakly alpha 1-adrenergic agonistic activities of tyramine, clonidine, and high concentrations of isoproterenol (10(-6)-10(-4) M). There was also a significant reduction in the tension developed by smooth muscles of the aortas from CA rats when depolarized with KCl in concentrations ranging from 8 to 20 mM. In contrast, aortic smooth muscle, contracted to 75% of maximum with KCl, showed an enhanced relaxation to the beta-adrenergic agonist, isoproterenol, in CA rats. These studies suggest that acclimation of rats to cold results in both a decrease in alpha-adrenergic responsiveness and an increase in beta-adrenergic responsiveness in vascular smooth muscle as well as a change in the biochemical events that couple activation of adrenergic receptors to changes in vasomotor tone.
Exercise responses in pregnant sheep: blood gases, temperatures, and fetal cardiovascular system
Authors: Lotgering F. K. , Gilbert R. D. , Longo L. D.
Published: December 2017

In an effort to examine the effects of maternal exercise on the fetus we measured maternal and fetal temperatures and blood gases and calculated uterine O2 consumption in response to three different treadmill exercise regimens in 12 chronically catheterized near-term sheep. We also measured fetal catecholamine concentrations, heart rate, blood pressure, cardiac output, blood flow distribution, blood volume, and placental diffusing capacity. Maternal and fetal temperatures increased a mean maximum of 1.5 +/- 0.5 (SE) and 1.3 +/- 0.1 degrees C, respectively. We corrected maternal and fetal blood gas values for the temperatures in vivo. Maternal arterial partial pressure of O2 (PO2), near exhaustion during prolonged (40 min) exercise at 70% maximal O2 consumption, increased 13% to a maximum of 116.7 +/- 4.0 Torr, whereas partial pressure of CO2 (PCO2) decreased by 28% to 27.6 +/- 2.2 Torr. Fetal arterial PO2 decreased 11% to a minimum of 23.2 +/- 1.6 Torr, O2 content by 26% to 4.3 +/- 0.6 ml X dl -1, PCO2 by 8% to 49.6 +/- 3.2 Torr, but pH did not change significantly. Recovery was virtually complete within 20 min. During exercise total uterine O2 consumption was maintained despite the reduction in uterine blood flow because of hemoconcentration and increased O2 extraction. The decrease of 3 Torr in fetal arterial PO2 and 1.5 ml X dl -1 in O2 content did not result in major cardiovascular changes or catecholamine release. These findings suggest that maternal exercise does not represent a major stressful or hypoxic event to the fetus.
Natural and artificial lung surfactant replacement therapy in premature lambs
Authors: Egan E. A. , Notter R. H. , Kwong M. S. , Shapiro D. L.
Published: December 2017

The effect of tracheal instillation of surface-active mixtures in premature lambs was studied as an animal model of exogenous surfactant replacement therapy for the respiratory distress syndrome (RDS). Specific mixtures studied were 7:3 (molar ratio) dipalmitoyl phosphatidylcholine (DPPC):egg phosphatidylglycerol (PG) and extracted mixed lipids (with 1% protein) from cow lung lavage (CLL). Preventilatory tracheal instillation of greater than 15 mg/kg of CLL in 10 ml 0.15 M NaCl to premature lambs gave improved alveolar-arterial O2 gradient and blood gases and increased lung compliance, compared with control lambs over a 15-h period. Lambs receiving 7:3 DPPC:PG dispersions were not improved over controls with regard to pressure-volume characteristics and were worse than controls in arterial oxygenation. In terms of in vitro surface properties, both extracted natural CLL and 7:3 DPPC:egg PG were able to lower aqueous surface tension to 1 dyn/cm under dynamic compression. However, the dynamic respreading of CLL films on successive surface cycles was superior to that of 7:3 DPPC:PG. Moreover, after dispersal in 0.15 M NaCl by vortexing (5 mg/80 ml), CLL adsorbed to surface pressure (tau values of 45 dyn/cm within 10 min. 7:3 DPPC:PG adsorbed to significantly lower tau values after subphase dispersal by a variety of methods.
Effect of blood volume on forearm venous and cardiac stroke volume during exercise
Authors: Fortney S. M. , Wenger C. B. , Bove J. R. , Nadel E. R.
Published: December 2017

Five healthy men exercised at 65-70% of maximum O2 uptake (VO2 max) for 30 min in an ambient temperature of 30 degrees C. Duplicate experiments were conducted at three levels of plasma volume:control, hypovolemia, in which blood volume (BV) was reduced an average of 490 ml (9.7%) with diuretics, and hypervolemia, in which BV was increased an average of 440 ml (7.8%) by infusing an isotonic solution containing 5% human serum albumin. Marked venoconstriction occurred during exercise in all conditions and persisted despite large increases in deep body temperature. The degree of venoconstriction was similar during control and hypervolemic conditions, but was potentiated during hypovolemia. The observed venoconstriction appeared to consist of two components: an early one related to autonomic adjustments at the onset of exercise, and a later one possibly related to progressive decreases in cardiac filling. Heart rate, cardiac stroke volume (SV), and cardiac output during exercise were significantly affected by changes in BV. During hypovolemia the average differences from control values were 10 beats X min-1, -14 ml, and -2.2 l X min-1, respectively; during hypervolemia the differences from control were -7 X min-1, 10 ml, and 1.0 l X min-1, respectively. The pattern of SV over the course of exercise indicates that pooling of blood in veins may be quantitatively more important than plasma water loss in reducing cardiac filling pressure in the heat.
Estimation of regional pleural surface expansile forces in intact dogs
Authors: Hoffman E. A. , Behrenbeck T. , Chevalier P. A. , Wood E. H.
Published: December 2017

Distances between percutaneously inserted apical and basal lung markers determined by biplane X-ray, computer-based videometry (J. Appl. Physiol. 34: 544, 1973) were calibrated against dependent percutaneously recorded pleural liquid pressures (J. Appl. Physiol. 31: 277, 1971) in five 10-12 kg mongrel dogs under morphine-pentobarbital anesthesia studied without thoracotomy. At the same apical pleural-liquid pressure values, the apical intermarker distances were uniformly greater when in the head-up rather than head-down position. This finding suggests that the expansile forces acting on the apical regions of the lung, in the head-up position, are greater (-30 +/- 2 cmH2O) than would be predicted from “pleural liquid” pressures (-15 +/- 1 cmH2O) measured at this nondependent site in the thorax, and much greater than the “pleural surface” pressures measured by the generally accepted balloon and counter-pressure techniques. In contrast, in the head-down body position, expansile forces acting on the nondependent basal regions of the lung estimated by the intermarker distance technique were variable to either side of the pressures measured by open-ended liquid-filled catheters, and thus were not significantly different. Mean values measured by the catheters and predicted by the markers were -14 +/- 1 and -10 +/- 3 cmH2O, respectively.
Response of pulmonary rapidly adapting receptors during lung inflation
Authors: Pack A. I. , DeLaney R. G.
Published: December 2017

Studies were conducted to establish the factors that determine the response of canine pulmonary rapidly adapting receptors (RAR) during lung inflation. Inflations of the lung were performed at several constant rates during which the activity of individual RAR was counted. At each rate of inflation tested multiple identical tests were performed. The volume of each test inflation was controlled. Data obtained in all tests at each flow rate were averaged to give the mean response of the receptor at that rate of inflation. These studies indicate the major response characteristics of RAR during lung inflation in conditions of relatively constant lung mechanics. First, at a constant rate of inflation, the activity of RAR augments increasingly as the lung is expanded. Second, their activity is influenced markedly by the rate of inflation. However, this sensitivity is nonlinear. Specifically, at low rates of inflation increases in flow rate produce more marked augmentation of RAR firing than do identical increases in flow at higher rates of inflation. The major difference between receptors is in their threshold; however, this too is a function of flow rate. With increasing flow rate the threshold, whether measured as the inflation volume or transpulmonary pressure at which receptors begin to fire, declines. The response of receptors, however, with thresholds over the entire range show the major features discussed above. The present results provide quantitative information which are necessary to begin to eludicate the transduction properties of this receptor type.