bluuebunny/crossref_metadata_2025 huggingface dataset:
In-line measurement of pulmonary metabolic function in the anesthetized rabbit
Authors: Pitt B. R. , Ryan J. W. , Chung A. Y. , Woodford M. , Yeates D. B. , Gillis C. N.
Published: December 2017

Quantitative assessment of lung metabolic function is thought to provide biochemical information reflecting integrity of the pulmonary microcirculation. Although multiple indicator-dilution techniques are useful in such pharmacokinetic studies, the need for fractionation and subsequent processing of blood samples greatly prolongs data generation. Accordingly, we designed and tested an in-line system which rapidly can quantify single-pass disposition of photon-emitting substances in the pulmonary circulation of intact animals. The nuclear detection system consisted of a phoswich scintillation probe optically coupled to a photomultiplier tube. Pulses were discriminated for height and shape and counts recorded in a counter-timer, the output of which was interfaced with a personal computer. A mixture of an intravascular reference substance (99mTc-sulfur colloid) and an inhibitor of angiotensin-converting enzyme, N-[1(S)-carboxy-(4-OH-3-[125I]-phenyl) ethyl]-L-alanyl-L-proline (125I-CPAP), was injected as a bolus in the right heart of anesthetized ventilated rabbits and arterial blood was diverted through a flow-cell cuvette directly apposed to the phoswich detector. Single-pass extraction of 125I-CPAP was 39 +/- 3% (mean +/- SE; n = 20) and was depressed in a dose-dependent fashion by the addition of unlabeled CPAP (1–10 micrograms/kg) to the injection. These data indicate that we can now quantify, in the intact animal, saturable binding of an inhibitor to angiotensin-converting enzyme expressed on the surface of the pulmonary microvascular endothelium. Furthermore, such data can be obtained rapidly.
Plasticity of skeletal muscle: regenerating fibers adapt more rapidly than surviving fibers
Authors: Donovan C. M. , Faulkner J. A.
Published: December 2017

The properties of mammalian skeletal muscle demonstrate a high degree of structural and functional plasticity as evidenced by their adaptability to an atypical site after cross-transplantation and to atypical innervation after cross-innervation. We tested the hypothesis that, regardless of fiber type, skeletal muscles composed of regenerating fibers adapt more readily than muscles composed of surviving fibers when placed in an atypical site with atypical innervation. Fast muscles of rats were autografted into the site of slow muscles or vice versa with the donor muscle innervated by the motor nerve to the recipient site. Surviving fibers in donor muscles were obtained by grafting with vasculature intact (vascularized muscle graft), and regenerating fibers were obtained by grafting with vasculature severed (free muscle graft). Our hypothesis was supported because 60 days after grafting, transposed muscles with surviving fibers demonstrated only a slight change from the contractile properties and fiber typing of donor muscles, whereas transplanted muscles with regenerating fibers demonstrated almost complete change to those of the muscle formerly in the atypical site.
ATP utilization and force during intermittent and continuous muscle contractions
Authors: Chasiotis D. , Bergstrom M. , Hultman E.
Published: December 2017

Energy utilization and force generation under anaerobic conditions were studied in electrically stimulated quadriceps femoris muscle of four volunteers. To investigate the effects of intermittent vs. continuous stimulation one leg was stimulated intermittently and the other continuously during 50 s. The same initial force was produced, and biopsy samples were obtained before the stimulation and after 10, 20, and 50 s and analyzed for energy-rich phosphagens, glycolytic intermediates, and phosphorylase. The ATP utilization and glycolysis were greater during intermittent contraction, but glycogenolysis was equal. ATP content decreased to lower values after intermittent contraction (16.4 compared with 19.6 mmol/kg dry muscle after continuous contraction). Force generation was well preserved during continuous contraction but successively decreased after 20 s of intermittent stimulation down to 50% of initial at end of work. The energy cost per unit work was greater during intermittent stimulation and increased with contraction time, whereas it decreased with time during continuous stimulation. The decrease in force generation in intermittent exercise is suggested to be due to the higher energy cost for contraction resulting in greater changes in the intracellular environment with lower ATP and increased H+ and Pi. These changes would decrease both activation of the contractile system and the cross-bridge turnover rate resulting from activation.
Cardiac output by rebreathing in patients with cardiopulmonary diseases
Authors: Kallay M. C. , Hyde R. W. , Smith R. J. , Rothbard R. L. , Schreiner B. F.
Published: December 2017

Noninvasive estimates of cardiac output by rebreathing soluble gases (Qc) can be unreliable in patients with cardiopulmonary diseases because of uneven distribution of ventilation to lung gas volume and pulmonary blood flow. To evaluate this source of error, we compared rebreathing Qc with invasive measurements of cardiac output performed by indicator-dilution methods (COID) in 39 patients with cardiac or pulmonary diseases. In 16 patients with normal lung volumes and 1-s forced expiratory volumes (FEV1), Qc measured with acetylene [Qc(C2H2)] overestimated COID insignificantly by 2 +/- 9% (SD). In subjects with mild to moderate obstructive lung disease, Qc(C2H2) slightly overestimated COID by 6 +/- 15% (P = 0.11). In patients with restrictive disease or combined obstructive and restrictive disease, Qc(C2H2) underestimated COID significantly by 9 +/- 14% (P less than 0.04). The magnitude of the discrepancy between Qc and COID correlated with size of the volume rebreathed and an index of uneven ventilation calculated from helium mixing during rebreathing that determined a dead space to inspired volume ratio (VRD/VI). Rebreathing volumes less than 40% of the predicted FEV or VRD/VI of 0.4 or greater identified all subjects with a discrepancy between Qc(C2H2) and COID of 20% or greater.
Breathing pattern during maximal exercise and during submaximal exercise with hypercapnia
Authors: Gallagher C. G. , Brown E. , Younes M.
Published: December 2017

During progressive exercise ventilation (VI) initially increases through increases in both tidal volume (VT) and respiratory frequency (f) but at high levels of exercise further increases in VI are almost completely due to increases in f and a VT plateau is seen. We wished to determine whether the presence of the VT plateau is due to a tachypneic influence related to very high levels of exercise or whether it represents a stereotypic response of the respiratory system at high levels of VI. We therefore compared breathing pattern in six subjects during maximal incremental exercise (ME) with that in the same subjects when similar levels of VI were obtained by a combination of submaximal exercise and hypercapnia (E/CO2). A VT plateau was seen in all ME and E/CO2 tests. There was no significant difference in the level of the VT plateau between the ME (2.93 +/- 0.17 liters) and E/CO2 (2.97 +/- 0.12 liters) tests. We conclude that the presence and level of the VT plateau during ME is not due to a tachypneic stimulus related to very high levels of exercise but is a function of the level of VI.
Muscle respiratory capacity and VO2 max in identically trained young and old rats
Authors: Cartee G. D. , Farrar R. P.
Published: December 2017

Old rats have a decreased hindlimb muscle respiratory capacity and whole-body maximal O2 consumption (VO2 max). The decline in spontaneous physical activity in old rats might contribute to these age-related changes. The magnitude of the age-related decline is not uniform in all skeletal muscle respiratory enzymes, and the decrease in palmitate oxidation is particularly great. This study was designed to determine if young and old rats subjected to the same exercise-training protocol would attain similar values for VO2 max and several markers of muscle respiratory capacity. Four- and 18-mo-old Fischer 344 rats underwent an identical 6-mo program of treadmill running. After training, both age groups had increased VO2 max above sedentary age-matched controls. However, the old trained rats had a lower VO2 max than identically trained young rats. In contrast to VO2 max, the two trained groups attained similar values for gastrocnemius citrate synthase, cytochrome oxidase, 3-hydroxyacyl-CoA dehydrogenase, palmitate oxidation, and total carnitine concentration. Thus, when the young and old rats performed an identical exercise protocol within the capacity of the old animals, differences in skeletal muscle respiratory capacity were eliminated. The dissimilarity in VO2 max between the identically trained groups was apparently caused by age-related differences in factors other than muscle respiratory capacity.
Alexander M. Kellas and the physiological challenge of Mt. Everest
Authors: West J. B.
Published: December 2017

Alexander M. Kellas (1868–1921) was a British physiologist who made pioneering contributions to the exploration of Everest and to the early physiology of extreme altitudes, but his physiological contributions have been almost completely overlooked. Although he had a full-time faculty position at the Middlesex Hospital Medical School in London, he was able to make eight expeditions to the Himalayas in the first two decades of the century, and by 1919 when the first official expedition to Everest was being planned, he probably knew more about the approaches than anybody else. But his most interesting contributions were made in an unpublished manuscript written in 1920 and entitled “A consideration of the possibility of ascending Mount Everest.” In this he discussed the physiology of acclimatization and most of the important variables including the summit altitude and barometric pressure, and the alveolar PO2, arterial oxygen saturation, maximal oxygen consumption, and maximal ascent rate near the summit. On the basis of this extensive analysis, he concluded that “Mount Everest could be ascended by a man of excellent physical and mental constitution in first-rate training, without adventitious aids [supplementary oxygen] if the physical difficulties of the mountain are not too great.” Kellas was one of the first physiologists to study extreme altitude, and he deserves to be better known.
Endothelial injury and pulmonary congestion characterize neurogenic pulmonary edema in rabbits
Authors: Minnear F. L. , Kite C. , Hill L. A. , van der Zee H.
Published: December 2017

The objectives of the present study were to determine whether an intracisternal injection of fibrinogen-sodium citrate, a model of neurogenic pulmonary edema (NPE), produces protein-rich or protein-poor pulmonary edema, and to determine whether the edema is associated with pulmonary vascular hypertension and pulmonary congestion. Fibrinogen (6–10 mg/ml) dissolved in 0.055 M sodium citrate was injected into the cisterna magna of six New Zealand White rabbits. Six additional rabbits were injected with saline to control for the effects of intracranial hypertension and pulmonary vascular hypertension. The fibrinogen-sodium citrate solution or sodium citrate alone, as opposed to saline, produced systemic and pulmonary vascular hypertension, pulmonary edema, hypoxemia, hypercapnia, and acidosis. The lungs from fibrinogen-injected rabbits were edematous, congested, and liverlike in appearance. Tracheal froth that was blood tinged and protein rich was present in five of the six rabbits. Microscopic examination of lung biopsies revealed erythrocytes and plasma in the alveoli and focal injury to the pulmonary microvascular endothelium. Fibrinogen-sodium citrate increased (P less than 0.05) the extravascular lung water (EVLW) (10.3 +/- 2.0 vs. 5.5 +/- 0.6 g, means +/- SE), lung blood weight (9.7 +/- 1.3 vs. 3.8 +/- 0.6 g), total dry lung weight (3.2 +/- 0.4 vs. 2.0 +/- 0.1 g), and the EVLW-to-blood-free dry lung weight ratio (7.0 +/- 0.8 vs. 4.0 +/- 0.3 g) from saline-control values. There was no difference in the blood-fre dry lung weight (1.4 +/- 0.1 vs. 1.3 +/- 0.1 g) between the two groups. These findings demonstrate that pulmonary congestion, pulmonary vascular hypertension, and focal endothelial injury contribute to the development of NPE.
Influence of upper airway sensory receptors on respiratory muscle activation in humans
Authors: Redline S. , Strohl K. P.
Published: December 2017

We reasoned that neural information from upper airway (UA) sensory receptors could influence the relationship between UA and diaphragmatic neuromuscular responses to hypercapnia. In this study, the electromyographic (EMG) activities of the alae nasi (AN), genioglossus (GG), and chest wall (CW) or diaphragm (Di) to ventilatory loading were assessed in six laryngectomized, tracheostomized human subjects and in six subjects breathing with an intact UA before and after topical UA anesthesia. The EMG activities of the UA and thoracic muscles increased at similar rates with increasing hypercapnia in normal subjects, in subjects whose upper airways were anesthetized, and in laryngectomized subjects breathing with a cervical tracheostomy. Furthermore, in the laryngectomized subjects, respiratory muscle EMG activation increased with resistive inspiratory loading (15 cmH2O X l–1 X s) applied at the level of a cervical tracheostomy. At an average expired CO2 fraction of 7.0%, resistive loading resulted in a 93 +/- 26.3% (SE) increase in peak AN EMG activity, a 39 +/- 2.0% increase in peak GG EMG activity, and a 43.2 +/- 16.5% increase in peak CW (Di) EMG activity compared with control values. We conclude that the ventilatory responses of the UA and thoracic muscles to ventilatory loading are not substantially influenced by laryngectomy or UA anesthesia.
Altitude acclimatization: influence on periodic breathing and chemoresponsiveness during sleep
Authors: White D. P. , Gleeson K. , Pickett C. K. , Rannels A. M. , Cymerman A. , Weil J. V.
Published: December 2017

Although the influence of altitude acclimatization on respiration has been carefully studied, the associated changes in hypoxic and hypercapnic ventilatory responses are the subject of controversy with neither response being previously evaluated during sleep at altitude. Therefore, six healthy males were studied at sea level and on nights 1, 4, and 7 after arrival at altitude (14,110 ft). During wakefulness, ventilation and the ventilatory responses to hypoxia and hypercapnia were determined on each occasion. During both non-rapid-eye-movement and rapid-eye-movement sleep, ventilation, ventilatory pattern, and the hypercapnic ventilatory response (measured at ambient arterial O2 saturation) were determined. There were four primary observations from this study: 1) the hypoxic ventilatory response, although similar to sea level values on arrival at altitude, increased steadily with acclimatization up to 7 days; 2) the slope of the hypercapnic ventilatory response increased on initial exposure to a hypoxic environment (altitude) but did not increase further with acclimatization, although the position of this response shifted steadily to the left (lower PCO2 values); 3) the sleep-induced decrements in both ventilation and hypercapnic responsiveness at altitude were equivalent to those observed at sea level with similar acclimatization occurring during wakefulness and sleep; and 4) the quantity of periodic breathing during sleep at altitude was highly variable and tended to occur more frequently in individuals with higher ventilatory responses to both hypoxia and hypercapnia.
In vivo contractile properties of fatigued diaphragm
Authors: Road J. , Vahi R. , del Rio P. , Grassino A.
Published: December 2017

The effects of fatigue on diaphragmatic contractility in vivo are unknown. In this study we used sonomicrometry to examine the velocity of shortening and lengthening and the amount of shortening in the fresh and fatigued canine hemidiaphragm (8 dogs) including the force generated. Fatigue was produced by epiphrenic stimulation of the left phrenic nerve; the right hemidiaphragm acted as the control. We found that 1) hemidiaphragmatic fatigue caused an increase in frequency with reduced tidal volume; 2) fatigue resulted in a near complete cessation of tidal shortening during spontaneous breathing; 3) there was an initial decrease in central activation (electromyogram) to the fatigued hemidiaphragm, an indication of central fatigue; 4) force-frequency curves showed a considerable and prolonged loss of the amount of shortening, velocity, and force generated by the fatigued hemidiaphragm during supramaximal stimulation, an indication of peripheral fatigue; and 5) during spontaneous breathing in the fatigued hemidiaphragm, tidal shortening remained reduced for up to 3 h, whereas in the right right hemidiaphragm tidal shortening and electromyographic activity did not change. We conclude that fatigue of a hemidiaphragm alters the spontaneous breathing pattern and produces profound modifications in its contractile properties without altering contralateral hemidiaphragmatic performance.
Upstream pressure for systemic to pulmonary flow from bronchial circulation in dogs
Authors: Agostoni P. G. , Deffebach M. E. , Kirk W. , Lakshminarayan S. , Butler J.
Published: December 2017

Systemic to pulmonary flow from bronchial circulation, important in perfusing potentially ischemic regions distal to pulmonary vascular obstructions, depends on driving pressure between an upstream site in intrathoracic systemic arterial network and pulmonary vascular bed. The reported increase of pulmonary infarctions in heart failure may be due to a reduction of this driving pressure. We measured upstream element for driving pressure for systemic to pulmonary flow from bronchial circulation by raising pulmonary venous pressure (Ppv) until the systemic to pulmonary flow from bronchial circulation ceased. We assumed that this was the same as upstream pressure when there was flow. Systemic to pulmonary flow from bronchial circulation was measured in left lower lobes (LLL) of 21 anesthetized open-chest dogs from volume of blood that overflowed from pump-perfused (90–110 ml/min) pulmonary vascular circuit of LLL and was corrected by any changes of LLL fluid volume (wt). Systemic to pulmonary flow from bronchial circulation upstream pressure was linearly related to systemic arterial pressure (slope = 0.24, R = 0.845). Increasing Ppv caused a progressive reduction of systemic to pulmonary flow from bronchial circulation, which stopped when Ppv was 44 +/- 6 cmH2O and pulmonary arterial pressure was 46 +/- 7 cmH2O. A further increase in Ppv reversed systemic to pulmonary flow from bronchial circulation with blood flowing back into the dog. When net systemic to pulmonary flow from bronchial circulation by the overflow and weight change technique was zero a small bidirectional flow (3.7 +/- 2.9 ml.min-1 X 100 g dry lobe wt-1) was detected by dispersion of tagged red blood cells that had been injected.(ABSTRACT TRUNCATED AT 250 WORDS)
Operation Everest II: preservation of cardiac function at extreme altitude
Authors: Reeves J. T. , Groves B. M. , Sutton J. R. , Wagner P. D. , Cymerman A. , Malconian M. K. , Rock P. B. , Young P. M. , Houston C. S.
Published: December 2017

Hypoxia at high altitude could depress cardiac function and decrease exercise capacity. If so, impaired cardiac function should occur with the extreme, chronic hypoxemia of the 40-day simulated climb of Mt. Everest (8,840 m, barometric pressure of 240 Torr, inspiratory O2 pressure of 43 Torr). In the five of eight subjects having resting and exercise measurements at the barometric pressures of 760 Torr (sea level), 347 Torr (6,100 m), 282 Torr (7,620 m), and 240 Torr, heart rate for a given O2 uptake was higher with more severe hypoxia. Slight (6 beats/min) slowing of the heart rate occurred only during exercise at the lowest barometric pressure when arterial blood O2 saturations were less than 50%. O2 breathing reversed hypoxemia but never increased heart rate, suggesting that hypoxic depression of rate, if present, was slight. For a given O2 uptake, cardiac output was maintained. The decrease in stroke volume appeared to reflect decreased ventricular filling (i.e., decreased right atrial and wedge pressures). O2 breathing did not increase stroke volume for a given filling pressure. We concluded that extreme, chronic hypoxemia caused little or no impairment of cardiac rate and pump functions.
Effects of autonomic blockade on cardiac function at rest and during upright exercise in humans
Authors: Kelbaek H. , Hartling O. J. , Gjorup T. , Marving J. , Christensen N. J. , Godtfredsen J.
Published: December 2017

The cardiac function was studied by radionuclide cardiography in eight healthy subjects at rest and during submaximal upright exercise before and after autonomic blockade with metoprolol and atropine. At rest the median stroke volume was reduced by 21% during autonomic blockade (P less than 0.01), but cardiac output was maintained by a concomitant increase in heart rate. The systolic blood pressure was reduced from 120 to 105 mmHg (P less than 0.01), and left ventricular ejection fraction was reduced from 61 to 56% (P less than 0.05). After autonomic blockade the heart rate reached during exercise was the same. Stroke volume and cardiac output were maintained through cardiac dilation. The increase in left ventricular end-diastolic volume was 31 vs. 10% during control conditions (P less than 0.01). The systolic blood pressure was reduced from 174 to 135 mmHg (P less than 0.01). Left ventricular ejection fraction was reduced from 75 to 67% (P less than 0.05), but the increase from rest to exercise was preserved. Total peripheral resistance was reduced by 17% (P less than 0.05). These findings suggest that the heart possesses intrinsic mechanisms to maintain cardiac output during submaximal upright exercise. End-diastolic dilation results in a preserved stroke volume despite a reduced contractility.
Naloxone reduces ventilatory depression of brain hypoxia
Authors: Neubauer J. A. , Posner M. A. , Santiago T. V. , Edelman N. H.
Published: December 2017

To assess whether endogenous opioids participate in respiratory depression due to brain hypoxia, we determined the ventilatory response to progressive carboxyhemoglobinemia (1% CO, 40% O2) before and after administration of naloxone (NLX, 0.1 mg/kg iv). Minute ventilation (VI) and ventral medullary surface pH (Vm pH) were measured in six anesthetized, peripherally chemodenervated cats. NLX consistently increased base-line hyperoxic VI from 618 +/- 99 to 729 +/- 126 ml/min (P less than 0.05). Although NLX did not alter the Vm pH response to CO [initial alkalosis, Vm pH +0.011 +/- 0.003 pH units, followed by acidosis, Vm pH -0.082 +/- 0.036 at carboxyhemoglobin (HbCO) 55%], NLX attenuated the amount of ventilatory depression; increasing HbCO to 55% decreased VI to 66 +/- 6% of base line before NLX and to 81 +/- 9% of base line after NLX (P less than 0.05). The difference in response after NLX was primarily the result of a linear increase in tidal volume (VT) with decreasing Vm pH (delta VT = 60.3 ml/-pH unit) which was absent before NLX. To assess whether the site of action of the endogenous opioid effect was the central chemosensors, the ventilatory and Vm pH response to progressive HbCO was determined in three additional cats before and after topical application of NLX (3 X 10(-4) M) to the ventral medullary surface. The effect of topical NLX was similar to systemic NLX; significant attenuation of the reduction in VI with increasing HbCO. We conclude that 1) endogenous opioids mediate a portion of the depression of ventilation due to acute brain hypoxia, and 2) this effect is probably at the central chemosensitive regions.
Patterns of EMG activity of rat plantaris muscle during swimming and other locomotor activities
Authors: Jasmin B. J. , Gardiner P. F.
Published: December 2017

The purpose of the study was to examine the patterns of electromyographic (EMG) activity of the rat plantaris during loaded swimming in comparison with other locomotor activities. Five female Sprague-Dawley rats were implanted with chronic bipolar electrodes in the plantaris muscle of the left hindlimb under pentobarbital anesthesia. Characteristics of EMG bursts recorded while the conscious rat was performing treadmill walking (0.24 m/s) were stable and reproducible 10–14 days postsurgery. Following this stabilization period, records of EMG activity were obtained during walking, loaded swimming (6.5 g attached to tail), and several other locomotor tasks. Compared to walking, EMG bursts during loaded swimming were significantly higher (67%) in maximum amplitude, one-third as long in duration, and occurred at a greater rate (4.4 vs. 1.7 bursts/s, P less than 0.05). Swimming bursts were of higher amplitudes than those of all other activities examined and reached 65% of the EMG amplitude recorded following stimulation of the sciatic nerve with supramaximal voltage. The addition of a mass to the animal's tail during swimming did not increase the EMG burst amplitudes but resulted in a higher frequency of bursts. Compared with treadmill walking, loaded swimming elicited burst of high variability in amplitude. Swimming in the rat involves rapid, extensive activation of plantaris, thus providing an exercise model to study the adaptability of the neuromuscular system to prolonged activity of this type.
Inhibitory effect of almitrine on dopaminergic activity of rat carotid body
Authors: Pequignot J. M. , Tavitian E. , Boudet C. , Evrard Y. , Claustre J. , Peyrin L.
Published: December 2017

Almitrine increases ventilation by stimulating the peripheral arterial chemoreceptors. This study assessed the effects of acute and chronic almitrine treatments on the dopamine (DA) and norepinephrine (NE) contents and utilization rates in the rat carotid body. Almitrine (5 mg/kg ip) caused a 34% reduction in DA content after 30 min. Extending the almitrine treatment for 15 days (one daily ip injection) produced a further progressive diminution in DA stores (-55%; P less than 0.01). The utilization rate of DA measured after inhibiting catecholamine biosynthesis by alpha-methyl-p-tyrosine was strongly reduced by almitrine (-98% after 15 days; P less than 0.01). The effects of almitrine were dose dependent. The noradrenergic activity was much less altered by the drug. The data showed that almitrine can modify the dynamics of DA in rat carotid body producing a decrease in both content and utilization rate.
Three-dimensional reconstruction of the rat acinus
Authors: Mercer R. R. , Crapo J. D.
Published: December 2017

This study provides a quantitative description of the small airways and alveolar duct-alveolar architecture of the rat lung. To accomplish this, quantitative three-dimensional reconstructions were made of small airways, the alveolar duct system, and alveoli. The branching pattern of the small airways immediately proximal to the alveolar ducts varied significantly. For example, the number of bronchiole-alveolar duct junctions per parent bronchus (terminal bronchiole) ranged from two to six. The number of bronchiole-alveolar duct junctions per lung was 7,280 +/- 250 (mean +/- SE). The general shape of the ventilatory unit arising from each bronchiole-alveolar junction was that of a space-filling sphere with an outer diameter of 1,490 +/- 130 microns. The average distance from the bronchiole-alveolar duct junction to alveoli at the end of the alveolar sac termination was 1,290 +/- 100 microns. Numerous trifurcations were found in the branching pattern of the alveolar ducts. The branching of the alveolar ducts did not fit a regular dichotomous pattern. The volume of the terminal branches (alveolar sacs) accounted for 64 +/- 5% of the volume of the ventilatory unit. Both of these factors, the pattern of branching and the substantial volume distributed in the most peripheral branches, contribute to the uniform distribution of gas within the ventilatory unit and thus minimize potential diffusion limitations to gas exchange.
Operation Everest II: man at extreme altitude
Authors: Houston C. S. , Sutton J. R. , Cymerman A. , Reeves J. T.
Published: December 2017

Rapid ascent to high altitude may cause serious problems for climbers, skiers, and aviators. In contrast, gradual ascent enables humans to function where the unacclimatized cannot. To examine changes in the O2 transport system that produce acclimatization, eight men were taken in a decompression chamber (without other stresses experienced on high mountains) to a simulated altitude of 8,840 m (29,028 ft, ambient PO2 = 43 Torr) in 40 days. Maximal O2 uptake fell to 1.2 l/min, and arterial PO2 and PCO2 were 30 and 11 Torr, respectively, with arterial pH of 7.56. Many sophisticated studies were done: Swan-Ganz catheterization and inert gas diffusion studies at three altitudes showed that normal cardiac function persisted, pulmonary vascular resistance increased and at extreme altitude was not lowered by O2, and pulmonary ventilation-perfusion mismatch increased, though variably. This appears to be an important factor limiting performance at extreme altitude. This paper presents the background, general approach, and a summary of major observations reported in detail in other papers.
Control of ventilation in elite synchronized swimmers
Authors: Bjurstrom R. L. , Schoene R. B.
Published: December 2017

Synchronized swimmers perform strenuous underwater exercise during prolonged breath holds. To investigate the role of the control of ventilation and lung volumes in these athletes, we studied the 10 members of the National Synchronized Swim Team including an olympic gold medalist and 10 age-matched controls. We evaluated static pulmonary function, hypoxic and hypercapnic ventilatory drives, and normoxic and hyperoxic breath holding. Synchronized swimmers had an increased total lung capacity and vital capacity compared with controls (P less than 0.005). The hypoxic ventilatory response (expressed as the hyperbolic shape parameter A) was lower in the synchronized swimmers than controls with a mean value of 29.2 +/- 2.6 (SE) and 65.6 +/- 7.1, respectively (P less than 0.001). The hypercapnic ventilatory response [expressed as S, minute ventilation (1/min)/alveolar CO2 partial pressure (Torr)] was no different between synchronized swimmers and controls. Breath-hold duration during normoxia was greater in the synchronized swimmers, with a mean value of 108.6 +/- 4.8 (SE) vs. 68.03 +/- 8.1 s in the controls (P less than 0.001). No difference was seen in hyperoxic breath-hold times between groups. During breath holding synchronized swimmers demonstrated marked apneic bradycardia expressed as either absolute or heart rate change from basal heart rate as opposed to the controls, in whom heart rate increased during breath holds. Therefore the results show that elite synchronized swimmers have increased lung volumes, blunted hypoxic ventilatory responses, and a marked apneic bradycardia that may provide physiological characteristics that offer a competitive advantage for championship performance.(ABSTRACT TRUNCATED AT 250 WORDS)
Physiologically derived critical evaporative coefficients for protective clothing ensembles
Authors: Kenney W. L. , Lewis D. A. , Hyde D. E. , Dyksterhouse T. S. , Armstrong C. G. , Fowler S. R. , Williams D. A.
Published: December 2017

When work is performed in heavy clothing, evaporation of sweat from the skin to the environment is limited by layers of wet clothing and air. The magnitude of decrement in evaporative cooling is a function of the clothing's resistance to permeation of water vapor. A physiological approach has been used to derive effective evaporative coefficients (he) which define this ability to evaporate sweat. We refined this approach by correcting the critical effective evaporative coefficient (K for sweating efficiency (Ke,eta') since only a portion of the sweat produced under such conditions is evaporated through the clothing. Six acclimated men and women walked at 30% maximal O2 consumption (150–200 W.m-2) at a constant dry bulb temperature as ambient water vapor pressure was systematically increased 1 Torr every 10 min. Critical pressure was defined as the partial pressure of water vapor (Pw) at which thermal balance could no longer be maintained and rectal temperature rose sharply. Each test was performed in various clothing ensembles ranging from cotton shirt and pants to “impermeable” suits. This approach was used to derive he by solving the general heat balance equation, M - W +/- (R + C) = w.he.(Psk - Pw), where M is metabolic heat production, W is external work, R is radiant heat exchange, C is convective heat transfer, w is skin wettedness, and Psk is water vapor pressure of fully wet skin.(ABSTRACT TRUNCATED AT 250 WORDS)
Gravity-independent inequality in pulmonary blood flow in humans
Authors: Hakim T. S. , Lisbona R. , Dean G. W.
Published: December 2017

Single-photon emission computerized tomography of the lung with 99mTc-labeled human albumin macroaggregates (99mTc-MAA) was used in six healthy subjects to study the three-dimensional distribution of pulmonary blood flow. 99mTc-MAA was injected while the subjects were resting in the supine position and holding their lung volume at normal end expiration. Tomography was performed on each subject from 120 projections of radioactivity in the lungs acquired with a rotating gamma camera. To minimize lung motion artifacts, the subjects were asked to hold their breath at end expiration during the 10-s duration of data acquisition in each projectional angle. Perfusion images of lung slices (11 mm thick) were reconstructed, and the radioactivity within each slice was expressed per unit lung volume of 3.7 X 3.7 X 11 mm. Perfusion images of a midcoronal slice from each subject manifested a concentric pattern of radioactivity that decreased significantly from the center to the periphery, suggesting that blood flow rate per unit lung volume was up to 10 times larger near the central region. This gradient in activity between the center and the periphery of the coronary slices was gravity independent as the subjects were supine. Images of sagittal slices from the middle of the right lung also manifested a similar pattern of concentric gradient in activity, with the vertical distribution (gravity related) almost comparable with the horizontal distribution (gravity independent). These results indicate that pulmonary blood flow in resting supine humans is spatially stratified with a marked central-to-peripheral gradient in all directions. It appears that zone 4 (reduced blood flow) is not a phenomenon limited to the dependent region of the lung as commonly thought but rather is a manifestation of this spatial distribution whereby blood flow is lowest in all peripheral regions of the lung.
Isometric contractile properties of diaphragm strips from alcoholic rats
Authors: Reid M. B. , Feldman H. A. , Miller M. J.
Published: December 2017

Chronic ethanol consumption alters the structure and function of human respiratory muscle. We have examined its effect on the active and passive mechanical properties of rat diaphragm strips in vitro. We conditioned eight rats using a liquid diet containing ethanol as 36% of calories. Eight control rats were pair-fed an isocaloric, ethanol-free liquid diet. Rats were killed after 23 wk. Two strips from the left hemidiaphragm were suspended in Krebs-Ringers solution at 25 degrees C, equilibrated with 5% CO2–95% O2. Isometric stresses were calculated from force transducer measurements. Strips were stimulated directly at supramaximal voltage. Twitch stress (Pt), measured at optimal length (Lo), was greater in ethanol-conditioned strips: 5.1 vs. 3.8 N/cm2. Times to peak Pt and twitch half-relaxation times were equal. Tetanic stress at Lo (Po) was also greater after ethanol conditioning: 17.2 vs. 12.8 N/cm2. Pt/Po ratios were equal. Expressed as %Po, tetanic stress-stimulation frequency curves and tetanic stress-length curves were identical. Ethanol-conditioned strips were marginally less compliant when passively stretched to lengths between Lo and 130% Lo. We postulate that ethanol may have increased active stress development by reducing intracellular free water.
Collagen and elastin fibers in human pulmonary alveolar mouths and ducts
Authors: Matsuda M. , Fung Y. C. , Sobin S. S.
Published: December 2017

To provide a quantitative basis for the understanding of the mechanical properties of the lung tissue, the morphology of the pulmonary alveolar ducts was studied and the dimensions of the collagen and elastin fiber bundles in the alveolar mouths were measured. Statistical data are presented in this report. It was found that the probability frequency functions of the widths of both the collagen and elastin fibers are skewed to the right, but the fourth roots of the widths are normally distributed. Hence, knowing the mean and standard deviation of (width)1/4, the probability of finding fiber bundles of width D is known. On the other hand, we already know the analytic expressions of the strain energy per unit length of fibers of given width. With the probability distribution of width and an estimation of the length of alveolar mouths, the strain energy of the alveolar mouths can be computed. Then the contribution of the alveolar mouths to the stress in the lung parenchyma due to any strain can be obtained by a differentiation of the strain energy function with respect to that strain.
Turbine flowmeter vs. Fleisch pneumotachometer: a comparative study for exercise testing
Authors: Yeh M. P. , Adams T. D. , Gardner R. M. , Yanowitz F. G.
Published: December 2017

The purpose of this study was to investigate the characteristics of a newly developed turbine flowmeter (Alpha Technologies, model VMM-2) for use in an exercise testing system by comparing its measurement of expiratory flow (VE), O2 uptake (VO2), and CO2 output (VCO2) with the Fleisch pneumotachometer. An IBM PC/AT-based breath-by-breath system was developed, with turbine flowmeter and dual-Fleisch pneumotachometers connected in series. A normal subject was tested twice at rest, 100-W, and 175-W of exercise. Expired gas of 24–32 breaths was collected in a Douglas bag. VE was within 4% accuracy for both flowmeter systems. The Fleisch pneumotachometer system had 5% accuracy for VO2 and VCO2 at rest and exercise. The turbine flowmeter system had up to 20% error for VO2 and VCO2 at rest. Errors decreased as work load increased. Visual observations of the flow curves revealed the turbine signal always lagged the Fleisch signal at the beginning of inspiration or expiration. At the end of inspiration or expiration, the turbine signal continued after the Fleisch signal had returned to zero. The “lag-before-start” and “spin-after-stop” effects of the turbine flowmeter resulted in larger than acceptable error for the VO2 and VCO2 measurements at low flow rates.
Cholinergic neuromodulation by prostaglandin D2 in canine airway smooth muscle
Authors: Tamaoki J. , Sekizawa K. , Graf P. D. , Nadel J. A.
Published: December 2017

To determine whether prostaglandin D2 (PGD2) modulates cholinergic neurotransmission in airway smooth muscle and, if so, what the mechanism of action is, we studied bronchial segments from dogs under isometric conditions in vitro. PGD2 (10(-8)-10(-5) M) elicited dose-dependent muscle contraction, which was reduced after blockade of muscarinic receptors, so that 50% effective dose (ED50) increased from 1.3 +/- 0.3 X 10(-6) to 3.9 +/- 1.0 X 10(-6) M by atropine (10(-6) M) (mean +/- SE, P less than 0.05). Physostigmine, at a concentration insufficient to alter base-line tension (10(-8) M), enhanced the PGD2-induced contraction and decreased ED50 to 6.4 +/- 0.5 X 10(-7) M (P less than 0.05). When added at the highest doses that did not cause spontaneous contraction (1.9 +/- 0.5 X 10(-7) M), PGD2 increased the contractile response to electrical field stimulation (1–50 Hz) by 21.9 +/- 6.6% (P less than 0.001). In contrast to this effect, the response to administered acetylcholine was not affected by PGD2. On the other hand, PGD2-induced augmentation of the response to electrical field stimulation (5 Hz) was further increased from 23.6 +/- 3.0 to 70.4 +/- 8.8% in the presence of physostigmine (10(-8) M) and was abolished by atropine but not affected by the alpha-adrenergic antagonist phentolamine or the histamine H1-blocker pyrilamine. These results suggest that the contraction of airway smooth muscle induced by PGD2 is in in part mediated by a cholinergic action and that PGD2 prejunctionally augments the parasympathetic contractile response, likely involving the accelerated release of acetylcholine at the neuromuscular junction.
Muscle blood flow and fiber activity in partially curarized rats during exercise
Authors: Glenn G. M. , Laughlin M. H. , Armstrong R. B.
Published: December 2017

We previously reported that low doses of d-tubocurarine attenuated glycogen loss in red muscles of rats during treadmill walking but that the initial hyperemia in the muscles was normal. The present studies were performed to 1) determine with electromyography (EMG) whether red muscle fiber activity is reduced in walking, curarized rats and 2) study muscle blood flow and glycogen loss during running with different doses of curare (dose response). At 0.5 min of treadmill walking (15 m/min), integrated EMG in vastus intermedius (VI) muscle was reduced by an average of 18% in curarized (60 micrograms/kg) rats, although blood flow (measured with microspheres) was the same as in saline control rats. Comparison of blood flows and glycogen loss in quadriceps muscles at 1 min of treadmill running (30 m/min) with different curare doses (20–60 micrograms/kg) demonstrated that red muscle glycogen loss was inversely related to curare dose but that blood flows in the same muscles were unaffected by curare. These findings provide support for our previous conclusion that at the initiation of low to moderate treadmill exercise, red muscle blood flow is not proportional to the activity or metabolism of the muscle fibers.
Initiating regular exercise protects against muscle atrophy from glucocorticoids
Authors: Czerwinski S. M. , Kurowski T. G. , O'Neill T. M. , Hickson R. C.
Published: December 2017

This study was undertaken to examine whether exercise can prevent glucocorticoid-induced muscle atrophy in previously untrained individuals and to evaluate whether the time of hormone administration is a determinant in the muscle's response to glucocorticoids. Female rats were divided into five groups: 1) a sedentary group that received cortisol acetate (CA, 100 mg/kg body wt); 2) a sedentary group that received the dosing vehicle (1% aqueous carboxymethyl cellulose); 3) an exercise group that received CA immediately after each exercise session; 4) an exercise group that received CA 90 min after each exercise session; and 5) an exercise group that received the vehicle. Steroid treatment and exercise (28.7 m/min for 90 min/day) were performed for 11 consecutive days. Initiation of training prevented muscle mass loss by 60% in plantaris (P) muscles and by 25% in gastrocnemius (G) muscles. Time of steroid injection was not related to the muscle sparing response. In the glucocorticoid-treated exercised rats, the activities of citrate synthase, a training marker, increased 60% in P and 37% in G. Thus the exercise appeared to cause a greater recruitment of P muscles. These data support the hypothesis that entering into an exercise program can be effective in retarding glucocorticoid-induced muscle atrophy. The degree of atrophy prevention, however, may be related to the extent that specific muscles are recruited during exercise.
Effects of acid-base imbalance on pulmonary angiotensin-converting enzyme in vivo
Authors: Toivonen H. J. , Catravas J. D.
Published: December 2017

The effects of acid-base balance disturbances on pulmonary endothelial angiotensin-converting enzyme (ACE) were studied in anesthetized mechanically ventilated rabbits. Enzyme function was estimated from [3H]benzoyl-Phe-Ala-Pro ([3H]BPAP) utilization under first-order reaction conditions during a single transpulmonary passage and expressed as 1) substrate metabolism (M), 2) Amax/Km (Amax being equal to the product of enzyme mass and the constant of product formation), and 3) (Amax/Km)/100 ml blood flow. When respiratory acidosis/alkalosis was produced by altering respiratory rate at constant airway pressure, substrate (BPAP) utilization varied proportionally to arterial pH and inversely proportionally to arterial PCO2 (PaCO2) (P less than 0.05). Percent BPAP metabolism (%M) ranged from 92 +/- 3 (respiratory alkalosis) to 85 +/- 3 (normal), 82 +/- 3 (respiratory acidosis), and 78 +/- 2% (severe respiratory acidosis). Amax/Km similarly decreased from 899 +/- 129 to 825 +/- 143, 601 +/- 74, and 450 +/- 34 ml/min, respectively, and (Amax/Km)/100 ml blood flow was reduced from 176 +/- 26 to 131 +/- 22, 111 +/- 12, and 97 +/- 5, respectively. However, when respiratory acidosis/alkalosis was produced by altering both respiratory rate and airway pressure, no changes were observed in either %M, Amax/Km or (Amax/Km)/100 ml blood flow. Similarly metabolic alkalosis or acidosis did not alter M, Amax/Km or (Amax/Km)/100 ml blood flow. These results indicate that pulmonary endothelial ACE function can be affected by acid-base disturbances, probably indirectly through changes in perfused microvascular surface area.
Heat and water flux in the intrathoracic airways and exercise-induced asthma
Authors: Gilbert I. A. , Fouke J. M. , McFadden E. R.
Published: December 2017

To explore the relationship between the flux of heat and water within the respiratory tract during exercise and recovery to the development of exercise-induced asthma (EIA), we recorded airstream temperature at multiple points throughout the tracheobronchial tree in 10 normal and 10 asthmatic subjects before, during, and after cycle ergometry. In both groups, the intra-airway temperature fell progressively as ventilation increased, and there were no significant differences between the thermal profiles of the two populations at rest or during exercise. Calculation of water losses and the osmolality of the airway surface fluid failed to demonstrate significant airway drying in either group. With cessation of the work load, the airstream temperature increased abruptly, rising two times more rapidly in the asthmatics than the normals. Since the major source of heat in these experiments is the bronchial circulation, our findings suggest a reaction sequence consisting of vasoconstriction and airway cooling during exercise followed by a rapid resupply of heat when exercise ceases. The latter may cause the hyperplastic capillary bed in the airways of asthmatics to develop an exaggerated rebound hyperemia which may lead to airway edema and EIA.