bluuebunny/crossref_metadata_2025 huggingface dataset:
Synergistic hormonal effects on lung maturation in fetal sheep
Authors: Schellenberg J. C. , Liggins G. C. , Manzai M. , Kitterman J. A. , Lee C. C.
Published: December 2017

Cortisol has minimal effects on lung maturation in fetal sheep before 130 days gestation. To test whether there is enhancement of cortisol action by other hormones, cortisol (F), triiodothyronine (T3), epinephrine (E), prolactin (PRL), and epidermal growth factor (EGF), alone or in combination, were infused into fetal sheep for 84 h between 124 and 128 days gestation. A mixture of F + T3 + PRL, but not any combination of two hormones, increased both distensibility [1.71 +/- 0.12 (SE) ml of air/g wet wt at 40 cmH2O, V40] and stability (1.16 +/- 0.09 ml of air per g wet wt at 5 cmH2O, V5) to near full-term values, above values resulting from treatment with F alone (0.91 +/- 0.12 and 0.43 +/- 0.09 ml/g, P less than 0.01). Only F had an effect when given alone, V40 increasing (P less than 0.05). Treatment with F + T3 (0.81 +/- 0.18 ml/g) and F + E (0.77 +/- 0.07 ml/g) increased V5 above values obtained with F alone (P less than 0.05). Alveolar saturated phosphatidylcholine (SPC) was higher after treatment with F + T3 (161 +/- 52 micrograms/g), F + T3 + PRL (156 +/- 53 micrograms/g, P less than 0.05), and F + E (113 +/- 40 micrograms/g, P = 0.07) than after F (12 +/- 3 micrograms/g). We conclude that F, T3, and PRL have a synergistic effect on the development of distensibility and stability of the ovine fetal lung.
Characterization of muscarinic receptor subtypes on human peripheral lung
Authors: Casale T. B. , Ecklund P.
Published: December 2017

To better define the role of muscarinic receptors in lung responses and airway diseases, we characterized the binding of the M1-specific antagonist, [3H]pirenzepine (PZ), and the nonspecific (M1- and M2-) antagonist, [3H]quinuclidinyl benzilate (QNB), to human peripheral lung tissue. Data obtained from 15 different lung specimens showed that the radioligands bound to single high-affinity sites with dissociation constant (Kd) values ranging from 1 to 9 nM for [3H]PZ and 0.03 to 0.46 nM for [3H]QNB. Comparison of total binding capacity values by equilibrium experiments with [3H]PZ, unlabeled PZ, and [3H]QNB indicates that approximately one-half of the total muscarinic binding sites in human peripheral lung binds PZ with high affinity (putative M1-subtypes). Kd values for muscarinic agents determined by competition experiments with [3H]PZ were consistent with the expected rank order of potency for interactions with muscarinic receptors. Characterization of the role of these muscarinic receptor subtypes in human lung responses may lead to the development of more selective therapeutic agents for the treatment of chronic obstructive airway diseases.
Responses of pulmonary vagal mechanoreceptors to high-frequency oscillatory ventilation
Authors: Wozniak J. A. , Davenport P. W. , Kosch P. C.
Published: December 2017

The discharge of 57 slowly adapting pulmonary stretch receptors (PSR's) and 16 rapidly adapting receptors (RAR's) was recorded from thin vagal filaments in anesthetized dogs. The receptors were localized and separated into three groups: extrathoracic tracheal, intrathoracic tracheal, and intrapulmonary receptors. The influence of high-frequency oscillatory ventilation (HFO) at 29 Hz on receptor discharge was analyzed by separating the response to the associated shift in functional residual capacity (FRC) from the oscillatory component of the response. PSR activity during HFO was increased from spontaneous breathing (49%) and from the static FRC shift (25%). PSR activity during the static inflation was increased 19% over spontaneous breathing. RAR activity was also increased with HFO. These results demonstrate that 1) the increased activity of PSR and RAR during HFO is due primarily to the oscillating action of the ventilator and secondarily to the shift in FRC associated with HFO, 2) the increased PSR activity during HFO may account for the observed apneic response, and 3) PSR response generally decreases with increasing distance from the tracheal opening.
Noninvasive diffusing capacity and cardiac output in exercising dogs
Authors: Carlin J. I. , Cassidy S. S. , Rajagopal U. , Clifford P. S. , Johnson R. L.
Published: December 2017

We have developed a rebreathing procedure to determine diffusing capacity (DLCO) and pulmonary blood flow (Qc) in the awake, exercising dog. A low dead space, leak-free respiratory mask with an incorporated mouthpiece was utilized to achieve mixing between the rebreathing bag and the dog's lung. The rebreathing bag was initially filled with approximately 1.0 liter of gas containing 0.6% C2H2, 0.3% C18O, 9% He, and 35-40% O2. End-tidal gas concentrations were measured with a respiratory mass spectrometer. The disappearance of C2H2 and C18O was measured with respect to He to calculate Qc and DLCO. Values for DLCO in dogs, expressed per kilogram of body weight, were much larger than those reported in humans. However, at a given level of absolute O2 consumption, measurements of absolute DLCO in dogs were comparable to those reported in humans by both rebreathing and steady-state methods at rest and near-maximal exercise. These results suggest that DLCO is more closely matched to the metabolic capacity (i.e., maximal O2 consumption) than to body size between these two species.
Influence of inspiratory flow rate and frequency on O2 cost of resistive breathing in humans
Authors: Dodd D. S. , Collett P. W. , Engel L. A.
Published: December 2017

We examined the combined effect of an increase in inspiratory flow rate and frequency on the O2 cost of inspiratory resistive breathing (VO2 resp). In each of three to six pairs of runs we measured VO2 resp in six normal subjects breathing through an inspiratory resistance with a constant tidal volume (VT). One of each pair of runs was performed at an inspiratory muscle contraction frequency of approximately 10/min and the other at approximately 30/min. Inspiratory mouth pressure was 45 +/- 2% (SE) of maximum at the lower contraction frequency and 43 +/- 2% at the higher frequency. Duty cycle (the ratio of contraction time to total cycle time) was constant at 0.51 +/- 0.01. However, during the higher frequency runs, two of every three contractions were against an occluded airway. Because VT and duty cycle were kept constant, mean inspiratory flow rate increased with frequency. Careful selection of appropriate parameters allowed the pairs of runs to be matched both for work rate and pressure-time product. The VO2 resp did not increase, despite approximately threefold increases in both inspiratory flow rate and contraction frequency. On the contrary, there was a trend toward lower values for VO2 resp during the higher frequency runs. Because these were performed at a slightly lower mean lung volume, a second study was designed to measure the VO2 resp of generating the same inspiratory pressure (45% maximum static inspiratory mouth pressure at functional residual capacity) at the same frequency but at two different lung volumes. This was achieved with a negligibly small work rate.(ABSTRACT TRUNCATED AT 250 WORDS)
Blood-brain barrier to hydrogen ion during acute metabolic acidosis in piglets
Authors: Wagerle L. C. , Kumar S. P. , Belik J. , Delivoria-Papadopoulos M.
Published: December 2017

The present study investigates the integrity of the blood-brain barrier to H+ or HCO3- during acute plasma acidosis in 35 newborn piglets anesthetized with pentobarbital sodium. Cerebrospinal fluid acid-base balance, cerebral blood flow (CBF), and cerebral oxygenation were measured after infusion of HCl (0.6 N, 0.191-0.388 ml/min) for a period of 1 h at a constant arterial PCO2 of 35-40 Torr. HCl infusion resulted in decreased arterial pH from 7.38 +/- 0.01 to 7.00 +/- 0.02 (P less than 0.01). CBF measured by the tracer microsphere technique was decreased by 12% from 69 +/- 6 to 61 +/- 4 ml.min-1.100 g-1 (P less than 0.05). Infusion of 0.6 N NaCl as a hypertonic control had no effect on CBF. Cerebral metabolic rate for O2 and O2 extraction was not significantly changed from control (3.83 +/- 0.20 ml.min-1.100 g-1 and 5.7 +/- 0.6 ml/100 ml, respectively) during acid infusion. Cerebral venous PO2 was increased from 41.6 +/- 2.1 to 53.8 +/- 4.0 Torr by HCl infusion (P less than 0.02) associated with a shift in O2-hemoglobin affinity of blood in vivo from 38 +/- 2 to 50 +/- 1 Torr. Cisternal cerebrospinal fluid pH decreased from 7.336 +/- 0.014 to 7.226 +/- 0.027 (P less than 0.005), but cerebrospinal fluid HCO3- concentration was not changed from control (25.4 +/- 1.0 meq/l). These data suggest that there is a functional blood-brain barrier in newborn piglets, that is relatively impermeable to HCO3- or H+ and maintains cerebral perivascular pH constant in the face of acute severe arterial acidosis. (ABSTRACT TRUNCATED AT 250 WORDS)
Effect of tracheal smooth muscle tone on collapsibility of immature airways
Authors: Penn R. B. , Wolfson M. R. , Shaffer T. H.
Published: December 2017

To test the influence of smooth muscle tone on extremely immature airways, tracheal segments (n = 19) were excised from premature lambs at 114-121 days gestation and mounted in a chamber filled with Krebs solution. Inflation (Si) and collapsing (Sc) compliance were determined by altering transmural pressure from 30 to 0 Torr and -30 to 0 Torr, respectively, both during control (C) and after acetylcholine (ACh) administration (experimental, E). Flow (V = 2-15 l/min) was then introduced through the tracheal lumen while chamber pressure (Pc) was increased from 0 to 30 Torr and driving pressure (Pd) was recorded for both C and E conditions. Tracheae were found to be extremely compliant; both Si and Sc were significantly (P less than 0.005) lower after ACh administration. Resistance to airflow (R = Pd/V) was also significantly (P less than 0.05) lower after ACh administration at each compressive pressure and each flow value. These results suggest that the highly compliant preterm trachea exhibits pressure-flow characteristics similar to a Starling resistor, and the effects of compressive pressures may be attenuated by ACh-induced smooth muscle contraction. Comparison of these results with data from adult and newborn animals suggests a developmental difference in tracheal mechanics and pressure-flow relationships, as well as in the way airway function is altered by smooth muscle stimulation.
Direct effects of CO on cerebral energy metabolism in bloodless rats
Authors: Piantadosi C. A. , Lee P. A. , Sylvia A. L.
Published: December 2017

Cerebrocortical b-cytochromes have been found to be sensitive to reduction in the presence of CO and O2 in vivo. CO-mediated cytochrome b reduction responses in "bloodless" rats were correlated in this study with changes in concentrations of high energy and glycolytic intermediates measured in cortex after rapid brain freezing. Cytochrome redox state and metabolite concentrations also were compared with cerebral blood flow (CBF) and cerebral metabolic rate for O2 (CMRo2) measured before and after CO administration. No definite biochemical evidence of energy limitation was found in parietal cortex after the fluorocarbon-for-blood exchange; however, CO had direct effects on brain metabolite concentrations. Fifteen-minute CO exposures at inspired CO/O2 of 0.003-0.06 increased cerebrocortical phosphocreatine and ADP and decreased creatine concentration. CO exposure produced no significant changes in either ATP concentration or CMRo2, although CBF increased slightly. These findings may be interpreted to indicate that CO binding to cytochrome aa3 at low CO/O2 in vivo increases extramitochondrial pH relative to that within the mitochondrial matrix. In the process, cytochrome b reduction levels increase, possibly signaling an increased efficiency of oxidative phosphorylation relative to O2 uptake by unblocked respiratory chains.
Glucose transport into rat skeletal muscle: interaction between exercise and insulin
Authors: Wallberg-Henriksson H. , Constable S. H. , Young D. A. , Holloszy J. O.
Published: December 2017

This study was done to evaluate the effect of insulin on sugar transport into skeletal muscle after exercise. The permeability of rat epitrochlearis muscle to 3-O-methylglucose (3-MG) was measured after exposure to a range of insulin concentrations 30, 60, and 180 min after a bout of exercise. Thirty and 60 min after exercise, the effects of exercise and insulin on 3-MG transport were additive over a wide range of insulin concentrations, with no increase in sensitivity or responsiveness to insulin. After 180 min, when approximately 66% of the exercise-induced increase in sugar transport had worn off, both the responsiveness and sensitivity of the glucose transport process to insulin were increased. These findings appear compatible with the hypothesis that the actions of exercise and insulin result in activation and/or translocation into the plasma membrane of two separate pools of glucose transporters in mammalian skeletal muscle.
Effects of altered CSF [H+] on ventilatory responses to exercise in the awake goat
Authors: Smith C. A. , Jameson L. C. , Dempsey J. A.
Published: December 2017

We investigated the effects of selective large changes in the acid-base environment of medullary chemoreceptors on the control of exercise hyperpnea in unanesthetized goats. Four intact and two carotid body-denervated goats underwent cisternal perfusion with mock cerebrospinal fluid (CSF) of markedly varying [HCO-3] (CSF [H+] = 21-95 neq/l; pH 7.68-7.02) until a new steady state of alveolar hypo- or hyperventilation was reached [arterial PCO2 (PaCO2) = 31-54 Torr]. Perfusion continued as the goats completed two levels of steady-state treadmill walking [2 to 4-fold increase in CO2 production (VCO2)]. With normal acid-base status in CSF, goats usually hyperventilated slightly from rest through exercise (-3 Torr PaCO2, rest to VCO2 = 1.1 l/min). Changing CSF perfusate [H+] changed the level of resting PaCO2 (+6 and -4 Torr), but with few exceptions, the regulation of PaCO2 during exercise (delta PaCO2/delta VCO2) remained similar regardless of the new ventilatory steady state imposed by changing CSF [H+]. Thus the gain (slope) of the ventilatory response to exercise (ratio of change in alveolar ventilation to change in VCO2) must have increased approximately 15% with decreased resting PaCO2 (acidic CSF) and decreased approximately 9% with increased resting PaCO2 (alkaline CSF). A similar effect of CSF [H+] on resting PaCO2 and on delta PaCO2/VCO2 during exercise also occurred in two carotid body-denervated goats. Our results show that alteration of the gain of the ventilatory response to exercise occurs on acute alterations in resting PaCO2 set point (via changing CSF [H+]) and that the primary stimuli to exercise hyperpnea can operate independently of central or peripheral chemoreception.
Bronchoconstriction elicited by isocapnic hyperpnea in guinea pigs
Authors: Ray D. W. , Hernandez C. , Munoz N. , Leff A. R. , Solway J.
Published: December 2017

We demonstrated spontaneous self-limited bronchoconstriction after eucapnic dry gas hyperpnea in 22 anesthetized, mechanically ventilated guinea pigs pretreated with propranolol (1 mg/kg iv). Eucapnic hyperpnea "challenges" of room temperature dry or humidified gas (5% CO2-95% O2) were performed by mechanically ventilating animals (150 breaths/min, 3-6 ml tidal volume) for 5 min. During a "recovery" period after hyperpnea, animals were returned to standard ventilation conditions (6 ml/kg, 60 breaths/min, 50% O2 in air, fully saturated at room temperature). After dry gas hyperpnea (5 ml, 150 breaths/min), respiratory system resistance (Rrs) increased in the recovery period by 7.7-fold and dynamic compliance (Cdyn) decreased by 79.7%; changes were maximal at approximately 3 min posthyperpnea and spontaneously returned to base line in 10-40 min. This response was markedly attenuated by humidification of inspired air. Four consecutive identical dry air challenges resulted in similar posthyperpnea responses in four animals. Increasing the minute ventilation during hyperpnea (by varying tidal volume from 3 to 6 ml) caused increased bronchoconstriction in a dose-dependent fashion in six animals. Neither vagotomy nor atropine altered the airway response to dry gas hyperpnea. We conclude that dry gas hyperpnea in anesthetized guinea pigs results in a bronchoconstrictor response that shares five similar features with hyperpnea-induced bronchoconstriction in human asthma: 1) time course of onset and spontaneous resolution, 2) diminution with humidification of inspired gas, 3) reproducibility on consecutive identical challenges, 4) stimulus-response relationship with minute ventilation during hyperpnea, and 5) independence of parasympathetic neurotransmission.
Importance of vagal afferents in determining ventilation in newborn rats
Authors: Fedorko L. , Kelly E. N. , England S. J.
Published: December 2017

We studied the effect of acute bilateral vagotomy on ventilation and ventilatory pattern in rats. In 1- to 6-day-old unanesthetized rats, vagotomy resulted in a substantial decrease (38%) in ventilation during air breathing. After vagotomy there was a threefold increase in tidal volume (VT), inspiratory time (TI) doubled, and expiratory time (TE) was six times longer. When studied under isoflurane anesthesia, newborn rats showed decreases in ventilation similar to that observed without anesthesia, whereas anesthetized adult rats had no consistent changes in ventilation. Adult and newborn rats had nearly identical proportionate increases in VT and TI after vagotomy, but TE lengthened to a greater extent in the newborns. Additionally, we demonstrated a significant decrease in ventilation when 100% O2 rather than air was supplied to nonvagotomized unanesthetized newborn rats. Ventilation decreased by 19% after vagotomy under hyperoxic conditions. We conclude that vagal afferent input, probably of pulmonary mechanoreceptor origin, provides positive feedback to respiration in newborn rats and that newborn rats greater than 24 h old also have a degree of peripheral chemoreceptor drive during air breathing.
Effect of stimulation of pulmonary C-fiber receptors on canine respiratory muscles
Authors: Haxhiu M. A. , van Lunteren E. , Deal E. C. , Cherniack N. S.
Published: December 2017

The effects of stimulation of pulmonary C-fiber receptors on the distribution of motor activity to upper airway, rib cage, and abdominal muscles were studied in anesthetized, tracheotomized, spontaneously breathing dogs. Stimulation of pulmonary C-fiber receptors by injection of capsaicin (3-20 micrograms/kg) into the right atrium resulted in complete cessation of electrical activity of the upper airway dilating muscles (UADM) and the inspiratory chest wall pumping muscles. The activity of abdominal muscles was also inhibited. The duration of electrical silence was longer for the diaphragm than for the UADM. Upper airway constricting muscles and expiratory intercostal muscles, including the triangularis sterni, remained tonically active during the apneic period. The responses of these muscles were qualitatively the same when the animals breathed 100% O2, 7% CO2 in O2, or 12% O2 in N2, and without or in the presence of an expiratory threshold load. Bilateral vagotomy abolished the inhibitory effects of capsaicin on UADM, chest wall, and abdominal muscle activity, suggesting that the vagus is the major afferent pathway for the reflex. The qualitative difference in the response of intercostal expiratory muscles and abdominal muscles suggests that these two groups of synergistic muscles may be independently regulated.
Role of muscle loss in the age-associated reduction in VO2 max
Authors: Fleg J. L. , Lakatta E. G.
Published: December 2017

A progressive decline in maximal O2 consumption (VO2max) expressed traditionally as per kilogram body weight generally occurs with advancing age. To investigate the extent to which this decline could be attributable to the age-associated loss of metabolically active tissue, i.e., muscle, we measured 24-h urinary creatinine excretion, an index of muscle mass, in 184 healthy nonobese volunteers, ages 22-87 yr, from the Baltimore Longitudinal Study of Aging who had achieved a true VO2max during graded treadmill exercise. A positive correlation was found between VO2max and creatinine excretion in both men (r = 0.64, P less than 0.001) and women (r = 0.47, P less than 0.001). As anticipated, VO2max showed a strong negative linear relationship with age in both men and women. Creatinine excretion also declined with age in men and women. When VO2max was normalized for creatinine excretion, the variance in the VO2max decline attributable to age declined from 60 to 14% in men and from 50 to 8% in women. Thus comparing the standard age regression of VO2max per kilogram body weight with that in which VO2max is normalized per milligram creatinine excretion, the decline in VO2max between a hypothetical 30 yr old and a 70 yr old was reduced from 39 to 18% in men and from 30 to 14% in women. We conclude that in both sexes, a large portion of the age-associated decline in VO2max in non-endurance-trained individuals is explicable by the loss of muscle mass, which is observed with advancing age.
Catalase pretreatment attenuates oleic acid-induced edema in isolated rabbit lung
Authors: Katz S. A. , Venkatachalam M. , Crouch R. K. , Heffner J. E. , Halushka P. V. , Wise W. C. , Cook J. A.
Published: December 2017

Because reactive O2 metabolites have been demonstrated to be potent mediators of vascular dysfunction and are synthesized by lung tissue, their involvement as mediators of oleic acid (OA)-induced pulmonary edema in the isolated Krebs-perfused rabbit lung was assessed. Injection of OA (0.1 ml) into the pulmonary artery after vehicle pretreatment induced marked increases in lung weight [50.4 +/- 13.9 vs. 4.2 +/- 2.0 (SE) g 45 min after OA or vehicle, respectively, P less than 0.05], an index of pulmonary edema, and airway pressure. OA also caused a significant though minimal increase in pulmonary arterial pressure. Pretreatment with catalase (1,000 U/ml), a scavenger of H2O2, significantly (P less than 0.05, Friedman's) attenuated the increases in lung weight (50.4 +/- 13.9 vs. 15.1 +/- 4.9 g), airway pressure, and pulmonary arterial pressure. In contrast to catalase, pretreatment with Cu-tryptophan (40 microM), a lipid-soluble scavenger of superoxide, provided no protective effect by itself, nor was there any potentiation of protection when combined with catalase. Further evidence implicating O2 metabolites in OA-induced edema was obtained by electron paramagnetic resonance (EPR) spectroscopy of perfusate samples to which the spin trap, sodium 3,5-dibromo-4-nitrosobenzenesulfonate (10 mM), was added. Analysis of these samples revealed the presence of free radicals after OA. Pretreatment with catalase (1,000 U/ml) and superoxide dismutase (250 U/ml) attenuated the EPR signal, indicating that proximal formation of O2 free radicals was in part responsible for the signal. These results suggest that reactive O2 metabolites are mediators of OA-induced pulmonary edema in the isolated perfused rabbit lung.
Thyroarytenoid muscle activity during wakefulness and sleep in normal adults
Authors: Kuna S. T. , Insalaco G. , Woodson G. E.
Published: December 2017

To determine the respiratory-related activity of the thyroarytenoid (TA) muscle in normal adults, intramuscular electromyographic recordings were performed in eight normal adult males during wakefulness and sleep. Phasic expiratory TA activity was present during normal tidal breathing in all subjects during wakefulness. Tonic activity was frequently present during inspiration. After an initial rapid rise in activity near the onset of expiration, phasic TA activity generally exhibited one of three different discharge patterns: a plateau, a progressive increase, or, less commonly, a progressive decrease in activity. In four of five subjects examined, peak TA activity during quiet breathing in wakefulness appeared to be directly related to time of expiration. At a particular lung volume above end-expiratory volume during wakefulness, measurements of expiratory resistance were directly related to the level of TA activity. TA activity disappeared during stable periods of non-rapid-eye-movement sleep and exhibited paroxysmal bursts of activity during rapid-eye-movement sleep. The results during wakefulness indicate that the TA contributes to an active adduction of the vocal cords in expiration and suggest the presence of an active laryngeal braking mechanism during exhalation.
Serum potassium during exercise in Hereford calves: influence of physical conditioning
Authors: Fosha-Dolezal S. R. , Fedde M. R.
Published: December 2017

We determined how rapidly serum potassium concentration ([K+]) increased, its magnitude, and how quickly it decreased during and after a 3.5-min exercise bout at maximal speed capability in eight Hereford steers, before and after physical conditioning. Serum [K+] values rose rapidly after the start of exercise and declined rapidly to within 7% of preexercise values 5 min after exercise ceased. Before physical conditioning, serum [K+] increased from an average of 4.19 meq/l at rest to 6.71 meq/l at the highest treadmill speed the animals could sustain (1.8-2.4 m/s at a 3 degrees incline). After physical conditioning, the serum [K+] increase at comparable treadmill speeds was approximately 5% lower than before conditioning (average of 6.37 meq/l); however, the animals could now exercise from 0.6 to 0.8 m/s faster than before conditioning, and their maximal serum [K+] rose to an average of 7.47 meq/l, a 10% increase over preconditioned maximal values. We conclude that higher speeds and accompanying increases in serum [K+] attained by conditioned animals may place them at greater risk of cardiotoxicity than before conditioning.
Differential responses of tissue viscance and collateral resistance to histamine and leukotriene C4
Authors: Ludwig M. S. , Shore S. A. , Fredberg J. J. , Drazen J. M.
Published: December 2017

Alterations in tissue viscance (Vti) and collateral resistance (Rcoll) are both used as indexes of peripheral lung responses. However, it is not known whether the two responses reflect the effects of activation of the same contractile elements. We measured differential responses in Vti and Rcoll to histamine and leukotriene (LT) C4 to determine whether each evoked a similar pattern of response. Using the wedged bronchoscope constant-flow technique, we measured Rcoll in lobar segments of anesthetized, paralyzed, open-chest, mechanically ventilated mongrel dogs. In addition, we measured (with an alveolar capsule) alveolar pressure (PA) within the segment under study. This allowed us to calculate Vti, the component of the PA change in phase with segment flow. Rcoll and Vti measurements were obtained under base-line conditions and after local delivery of aerosols generated from histamine and LTC4. In five out of five lobes studied with both histamine and LTC4, the fractional Rcoll response to histamine was greater than the fractional Rcoll response to LTC4. In contrast, in four out of five lobes examined, the fractional increase in Vti accompanying the histamine response was less than the fractional increase in Vti accompanying LTC4 administration. These data suggest that anatomically distinct contractile elements influence Vti and Rcoll insofar as LTC4 and histamine evoke quantitatively different changes in these two indexes of peripheral lung responses.
Kainic acid on the rostral ventrolateral medulla inhibits phrenic output and CO2 sensitivity
Authors: Nattie E. E. , Mills J. W. , Ou L. C. , St John W. M.
Published: December 2017

We used the neurotoxin, kainic acid, which is known to stimulate neuronal cell bodies as opposed to axons of passage by binding to specific amino acid receptors to determine whether cells with such receptors have access to the ventrolateral medullary surface and are involved in central ventilatory chemosensitivity. Pledgets with 4.7 mM kainic acid were placed bilaterally on the rostral, intermediate, or caudal ventilatory chemosensitive areas for 1-2 min in chloralose-urethan-anesthetized, paralyzed, vagotomized, glomectomized, and servo-ventilated cats. Application of kainic acid on the caudal or intermediate areas produced no consistent significant effects on eucapnic phrenic output or on the slope or maximum value of the phrenic nerve response to increased end-tidal PCO2. Rostral area kainic acid produced immediate augmentation and then diminution of blood pressure and phrenic output. Apnea developed in six of nine cats by 40 min. In all five cats in which it could be tested, the slope of the CO2 response was clearly decreased. Of [3H]kainic acid applied to the rostral area, 88.4% was shown to be within 2 mm of the ventral surface. Comparison of surface application sites of this and other studies suggests that an area overlapping the border of the original rostral and intermediate areas allows access to neurons involved in the chemoreception process, which may also provide tonic facilitatory input to cardiorespiratory systems.
Morphometric measurement of local curvature of the alveolar ducts in lung mechanics
Authors: Silage D. A. , Gil J.
Published: December 2017

We have performed partial serial reconstructions of an acinus of the rabbit lung and determined the apparent existence of numerous heterogeneities in length, diameter, and local curvature in individual generation branches of the lung. We believe that structural changes during respiratory movements may include changes in the length and diameter of the whole duct. Alveoli are seen to be side differentiations secondary to the ducts in the gas-exchanging parenchyma of the rabbit lung. We have developed a technique for measuring local curvature in simple reconstructed ducts from the average of the integral curvation of the section contour. The contour curvature is measured from the chain code representation of the sampled contour from digital image analysis. The stereological requirements of an unbiased and random selection of contours is approached here by the random orientation of the individual alveoli of a single duct. Over 700 sections through the last four airway generations (alveolar ducts) at 3-micron intervals were analyzed. The average integral curvature ranges from 7.7 to 9.5 (mean 8.9) mm-1 for sixth- and seventh-generation branches from the start with volumes for the segments from 0.022 to 1.198 (mean 0.497) mm3.
Correction of inert gas washin or washout for gas solubility in blood
Authors: Harris E. A. , Whitlock R. M.
Published: December 2017

We show that when an inert gas is washed into the lungs its retention in the blood during any one breath is approximately proportional to its solubility. This relationship makes possible the correction of washin or washout data for blood uptake or release, provided that two gases of different solubility are used simultaneously. The method automatically allows for the characteristics of an individual washin or washout and for the occurrence of recirculation within a fairly short washin or washout period. It has been tested in models with nonuniform ventilation and perfusion and closely approximates the behavior of a truly insoluble gas. In the derived ventilation distribution, gas solubility appears as ventilation to units of low turnover. In the case of N2 this effect is small but causes appreciable overestimation of lung volume. The recovered dead space and main alveolar distribution are insignificantly affected.
Effect of carbohydrate feedings during high-intensity exercise
Authors: Coggan A. R. , Coyle E. F.
Published: December 2017

To determine the upper limits of steady-state exercise performance and carbohydrate oxidation late in exercise, seven trained men were studied on two occasions during prolonged cycling that alternated every 15 min between approximately 60% and approximately 85% of VO2max. When fed a sweet placebo throughout exercise, plasma glucose and respiratory exchange ratio (R) declined (P less than 0.05) from 5.0 +/- 0.1 mM and 0.91 +/- 0.01 after 30 min (i.e., at 85% VO2max) to 3.7 +/- 0.3 mM and 0.79 +/- 0.01 at fatigue (i.e., when the subjects were unable to continue exercise at 60% VO2max). Carbohydrate feeding throughout exercise (1 g/kg at 10 min, then 0.6 g/kg every 30 min) increased plasma glucose to approximately 6 mM and partially prevented this decline in carbohydrate oxidation, allowing the men to perform 19% more work (2.74 +/- 0.13 vs. 2.29 +/- 0.09 MJ, P less than 0.05) before fatiguing. Even when fed carbohydrate, however, by the 3rd h of exercise, R had fallen from 0.92 to 0.87, accompanied by a reduction in exercise intensity from approximately 85% to approximately 75% VO2max (both P less than 0.05). These data indicate that carbohydrate feedings enable trained cyclists to exercise at up to 75% VO2max and to oxidize carbohydrate at up to 2 g/min during the later stages of prolonged intense exercise.
Costal diaphragmatic O2 and lactate extraction in laryngeal hemiplegic ponies during exercise
Authors: Manohar M. , Goetz T. E. , Nganwa D.
Published: December 2017

Diaphragmatic O2 and lactate extraction were examined in seven healthy ponies during maximal exercise (ME) carried out without, as well as with, inspiratory resistive breathing. Arterial and diaphragmatic venous blood were sampled simultaneously at rest and at 30-s intervals during the 4 min of ME. Experiments were carried out before and after left laryngeal hemiplegia (LH) was produced. During ME, normal ponies exhibited hypocapnia, hemoconcentration, and a decrease in arterial PO2 (PaO2) with insignificant change in O2 saturation. In LH ponies, PaO2 and O2 saturation decreased well below that in normal ponies, but because of higher hemoglobin concentration, arterial O2 content exceeded that in normal ponies. Because of their high PaCO2 during ME, acidosis was more pronounced in LH animals despite similar lactate values. Diaphragmatic venous PO2 and O2 saturation decreased with ME to 15.5 +/- 0.9 Torr and 18 +/- 0.5%, respectively, at 120 s of exercise in normal ponies. In LH ponies, corresponding values were significantly less: 12.4 +/- 1.3 Torr and 15.5 +/- 0.7% at 120 s and 9.8 +/- 1.4 Torr and 14.3 +/- 0.6% at 240 s of ME. Mean phrenic O2 extraction plateaued at 81 and 83% in normal and LH animals, respectively. Significant differences in lactate concentration between arterial and phrenic-venous blood were not observed during ME. It is concluded that PO2 and O2 saturation in the phrenic-venous blood of normal ponies do not reach their lowest possible values even during ME. Also, the healthy equine diaphragm, even with the added stress of inspiratory resistive breathing, did not engage in net lactate production.
Atrial natriuretic peptide lowers pulmonary arterial pressure in hypoxia-adapted rats
Authors: Jin H. K. , Yang R. H. , Thornton R. M. , Chen Y. F. , Jackson R. , Oparil S.
Published: December 2017

To test the hypothesis that atrial natriuretic peptide (ANP) has a direct vasodilator effect on the pulmonary vasculature that is enhanced in hypoxia-induced pulmonary hypertension in the rat, we determined the effects of ANP on mean pulmonary (MPAP) and systemic arterial pressure (MSAP) in intact conscious Sprague-Dawley rats exposed to 10% O2 or room air for 4 wk. Catheters were placed in the pulmonary artery through the right jugular vein by means of a closed-chest technique. MPAP and MSAP were monitored before and after intravenous injections of graded doses of ANP. ANP produced dose-related decreases in MPAP that were greater in the hypoxic group than in air controls. There were no significant between-group differences in the systemic depressor responses to ANP or in the ANP-induced reduction in cardiac output. ANP lowered MPAP significantly in isolated perfused lungs from both hypoxia-adapted and air control rats, and this effect was significantly greater in the hypoxic than the air control lungs. These data indicate that ANP lowers pulmonary arterial pressure in rats with hypoxia-induced pulmonary hypertension, mainly by a direct vasodilator effect on the pulmonary vasculature.
Inhomogeneity during deflation of excised canine lungs. III. Single-breath O2 tests
Authors: Warner D. O. , Hyatt R. E. , Rehder K.
Published: December 2017

Both interregional and intraregional mechanisms may cause changes in N2 concentration of expired gas during the phases of the single-breath O2 test (SBO2) that follow dead-space washout. To evaluate the possible importance of each mechanism, we performed the SBO2 in excised canine lungs that were first suspended in air and then immersed in stable foams that simulated the vertical gradient of pleural pressure. The lungs were deflated at constant submaximal flows. The slope of phase III diminished with increasing expiratory flow and increased with foam immersion. The onset of phase IV depended on flow, and a terminal decrease in N2 concentration (phase V) was often observed. Simultaneously measured estimates of regional flows and volumes (J. Appl. Physiol. 65: 1764-1774, 1988) were used to further interpret these results. The onset of phase IV at flows greater than quasi-static signified the onset of flow limitation of dependent regions. The onset of phase V corresponded to flow limitation of nondependent regions.
Roles of CO2, O2, and acid in arteriovenous [H+] difference during muscle contractions
Authors: Stainsby W. N. , Eitzman P. D.
Published: December 2017

To determine the origins of the arteriovenous [H+] difference of muscle during contractions, arterial and muscle venous blood sample pairs were taken before and after 0.5, 5.0, and 30.0 min of 4/s isometric twitches of the gastrocnemius-plantaris muscle group of anesthetized dogs. These samples were analyzed for PO2, PCO2, and pH, the concentrations of O2, CO2, K+, Na+, La-, and Cl- in whole blood, and La-, K+, Na+, and Cl- in plasma. Whole blood was hemolyzed and analyzed for PO2, PCO2, and pH. Net O2 uptake, CO2 output, L, K+, Na+, and Cl- were calculated in addition to net output of non-CO2 acid (HA) and strong ion difference ([SID]) and common ion [SID] ([K+] + [Na+] - [Cl-] - [La-]). From these data we partitioned the origins of the arteriovenous [H+] difference via the common PCO2-pH diagram and via a [H+]-PCO2 diagram and determined whether true plasma arteriovenous [H+] differences reflect plasma and cell arteriovenous [H+] differences. The arteriovenous [H+] differences of plasma and hemolyzed blood were the same, showing that true plasma does reflect plasma and cells. K+ showed a small significant but transient output. Na+ was not significant, whereas Cl- showed a significant transient uptake. Lactate output and HA, calculated for dog blood acid-base, showed transient outputs and were the same. At 5.0 min when the arteriovenous difference was largest, CO2 alone would have increased [H+] 15.9 nmol/l whereas desaturation of Hb would have decreased [H+] 4.2 nmol/l and lactate could have raised [H+] 1.0 nmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)
Hindlimb suspension increases insulin binding and glucose metabolism
Authors: Bonen A. , Elder G. C. , Tan M. H.
Published: December 2017

After 28 days of hindlimb-suspension, insulin binding, 2-deoxy-D-glucose (2-DG) uptake, and glucose metabolism (glycolysis and glycogenesis) were determined at various insulin concentrations (0.2-30 nM) in soleus muscle of young (18-day-old) and adult (150-day-old) rats. Compared with age-matched controls the young (YS) and adult suspended (AS) rats had lower soleus and body weights and insulin levels (P less than 0.05). Per milligram of protein, insulin binding, 2-DG uptake, and the rate of glycolysis were increased by approximately 200%, and the rate of glycogenesis was increased approximately 100% in the YS group (P less than 0.05). Except for a reduction in glycogenesis (P less than 0.05) all other parameters also increased in the AS rats (P less than 0.05). On the basis of the whole muscle the rate of glucose metabolism (glycogenesis + glycolysis) was reduced in the YS rats (P less than 0.05), but in the AS rats glucose metabolism was similar to the controls. Thus the increased glucose metabolism (i.e., per milligram of protein) in the YS and AS groups may represent a compensatory response by atrophied muscle to attempt to sustain glucose removal from the circulation. Because greater insulin binding occurred in YS muscle [35% slow-twitch (ST)] than in the control group (70% ST), and greater insulin binding occurred in the AS (81% ST) than in the control group (90% ST), higher insulin binding capacities are not always related to a high proportion of ST muscle fibers. In conclusion, after hindlimb suspension, marked increments in insulin binding and glucose metabolism occur in the soleus muscle.
Human circadian rhythms in temperature, trace metals, and blood variables
Authors: Scales W. E. , Vander A. J. , Brown M. B. , Kluger M. J.
Published: December 2017

The literature supports the concept that circadian changes in body temperature reflect changes in the thermoregulatory set point. We were interested in studying the relationship between the circadian rhythm in body temperature and 24-h variations in plasma concentrations of iron, zinc, circulating leukocyte counts, and plasma interleukin 1 (IL-1) activity. Eight healthy men were studied for two separate 48-h sessions. Rectal temperature, plasma iron and zinc concentrations, plasma IL-1 activity, circulating leukocyte counts, and several other blood variables were monitored. Circadian rhythms in temperature, trace metals, and various leukocyte populations were demonstrated. The 24-h pattern of changes in plasma concentrations of iron and zinc approximate an inverse relationship with rectal temperature. Although we were unable to detect any IL-1 activity in human plasma collected at 4-h intervals, the daily changes in plasma trace metal concentrations and the variations in leukocyte populations may provide indirect evidence for a daily variation in local (e.g., in liver) or central nervous system release of IL-1.
Effect of perivascular electromagnetic flow probes on pulmonary hemodynamics
Authors: Grant B. J. , Paradowski L. J. , Fitzpatrick J. M.
Published: December 2017

We determined the effect of perivascular electromagnetic flow probes (EMF) on pulmonary hemodynamics in acute experiments. In seven dogs placement of the EMF on the main pulmonary artery (MPA) increased pulmonary arterial pulse pressure by 25% (17.8-21.9 cmH2O, P less than 0.005) and mean right ventricular pressure by 12% (23.2-25.9 cmH2O, P less than 0.001) but did not alter heart rate, systemic blood pressure, mean pulmonary arterial pressure, or right ventricular end-diastolic pressure. This response was not abolished by local application of lidocaine to the MPA. In three cats input impedance was calculated from measurements of pressure and flow in the MPA. Impedance was calculated with flow measured using an EMF and ultrasonic volume flow probe (USF), which avoids the constraining effect of the EMF. When flow was measured with an EMF rather than a USF, there was a significant difference in the impedance spectra (P less than 0.001), but it was only apparent in the moduli greater than six harmonics. We conclude that the EMF does affect right ventricular afterload in acute experiments and alters the measured input impedance.
A muscarinic receptor subtype modulates vagally stimulated bronchial contraction
Authors: Bloom J. W. , Baumgartener-Folkerts C. , Palmer J. D. , Yamamura H. I. , Halonen M.
Published: December 2017

An in vitro preparation was developed to study vagus nerve-stimulated (preganglionic) and field-stimulated (post-ganglionic) contraction of the rabbit main stem bronchus and to compare the inhibitory effects of muscarinic antagonists on that contraction. The maximal contractile responses (20 V, 0.5 ms, 64 Hz) for either field or vagal stimulation were completely abolished by atropine (60 nM). Hexamethonium (0.1 mM) abolished the response to vagal stimulation but did not affect the field-stimulated response. To compare the effectiveness of atropine and pirenzepine as antagonists at the nerve-smooth muscle junction, inhibition studies of field-stimulated contractions were performed. Pirenzepine was 102- to 178-fold less potent than atropine when compared at the inhibitory concentration of antagonist that produced 25, 50, and 75% inhibition (IC25, IC50, and IC75, respectively), indicating that the muscarinic receptor at the nerve-smooth muscle junction is a muscarinic receptor with low affinity for pirenzepine (M2 subtype). Atropine had similar inhibitory effects on vagal- and field-stimulated contractions. In contrast, pirenzepine was more potent in inhibiting vagally stimulated contraction than field-stimulated contraction, especially at the IC25 where pirenzepine was only 8- to 22-fold less potent than atropine in inhibiting vagally stimulated contraction. These data suggest that an M1 subtype of muscarinic receptor modulates excitatory neurotransmission through bronchial parasympathetic ganglia.
Clearance of surfactant phosphatidylcholine via the upper airways in rabbits
Authors: Pettenazzo A. , Jobe A. , Humme J. , Seidner S. , Ikegami M.
Published: December 2017

A possible route of clearance of surfactant phosphatidylcholine from the lungs is via the airways. To quantify surfactant loss via this pathway, latex bags were surgically placed into the abdomens of adult rabbits such that secretions cleared via the esophagus could be collected. The rabbits then were given treatment or trace doses of radiolabeled phosphatidylcholine-surfactant by tracheal injection and/or intravascular radiolabeled precursors of phosphatidylcholine. Labeled saturated phosphatidylcholine was measured in all fluids that were collected from the bags at 2-h intervals for 24 h and in alveolar washes and lung tissues at 24 h. No more than 7% of either treatment or trace doses of intratracheal surfactant-saturated phosphatidylcholine was lost via clearance up the airways over 24 h. Clearances of endogenously synthesized and secreted saturated phosphatidylcholine were estimated to be no more than 3% of the flux of labeled saturated phosphatidylcholine through the alveolar pool. These experiments demonstrate that surfactant phosphatidylcholine clearance via movement up the airways is not a major pathway leading to surfactant catabolism.
Stimulation of H fields of Forel decreases total lung resistance in dogs
Authors: McCallister L. W. , Connelly J. C. , Kaufman M. P.
Published: December 2017

Although there is considerable evidence that the H fields of Forel of the posterior diencephalon play an important role in the regulation of cardiovascular function, little is known about the role these areas play in the control of airway caliber. In chloralose-anesthetized paralyzed dogs, we used both electrical and chemical means to stimulate the H fields of Forel, while we monitored breath-by-breath changes in total lung resistance (TLR), a functional index of airway caliber. Electrical stimulation (200-250 microA, 80 Hz, 0.75 ms) of 82 histologically confirmed sites significantly decreased TLR from 9.2 +/- 0.4 to 7.9 +/- 0.4 cmH2O.l-1.s (P less than 0.01). The bronchodilation evoked by electrical stimulation was unaffected by beta-adrenergic blockade with propranolol but was abolished by cholinergic blockade with atropine. The increases in airway caliber evoked by stimulation were often accompanied by increases in phrenic nerve activity. Chemical stimulation of 21 of 82 sites with microinjections of DL-homocysteic acid (83 nl, 0.2 and 0.5 M), which stimulates cell bodies but not fibers of passage, also decreased TLR from 8.3 +/- 0.5 to 7.3 +/- 0.5 cmH2O.l-1.s (P less than 0.03). We conclude that stimulation of cell bodies in the H fields of Forel produces bronchodilation by withdrawal of cholinergic tone to airway smooth muscle.