bluuebunny/crossref_metadata_2025 huggingface dataset:
Oronasal partitioning of ventilation during exercise in humans
Authors: Wheatley J. R. , Amis T. C. , Engel L. A.
Published: December 2017

The partitioning of oronasal breathing was studied in five normal subjects during progressive exercise. Subjects performed three to five identical runs, each consisting of four 1-min work periods at increments of 50 W. Nasal and oral airflow were measured simultaneously using a partitioned face mask both during and for 4 min after exercise. Total mean flows were the sum of nasal and oral flows. At a total mean inspiratory flow of 2 l/s, the nasal fraction of total flow was 0.36 +/- 0.04 (SE) and decreased by 6 +/- 3% between total flows of 1.5 and 2.5 l/s. Throughout exercise, the nasal fraction of total mean inspiratory flow did not differ from that of total expiratory flow and was similar to that of total mean inspiratory flow during the postexercise period at a corresponding total mean flow (both P greater than 0.02). The results show that oronasal flow partitioning is not directly due to the exercise itself but is related to the level of ventilation and is uninfluenced by the direction of upper airway flow (i.e., inspiratory vs. expiratory). These findings suggest tightly controlled modulation of the relative resistances of the oral and/or nasal pathways.
A cross-sectional study of muscle strength and mass in 45- to 78-yr-old men and women
Authors: Frontera W. R. , Hughes V. A. , Lutz K. J. , Evans W. J.
Published: December 2017

The isokinetic strength of the elbow and knee extensors and flexors was measured in 200 healthy 45- to 78-yr-old men and women to examine the relationship between muscle strength, age, and body composition. Peak torque was measured at 60 and 240 degrees/s in the knee and at 60 and 180 degrees/s in the elbow by use of a Cybex II isokinetic dynamometer. Fat-free mass (FFM) was estimated by hydrostatic weighing in all subjects, and muscle mass (MM) was determined in 141 subjects from urinary creatinine excretion. FFM and MM were significantly lower (P less than 0.001) in the oldest group. Strength of all muscle groups at both testing speeds was significantly (P less than 0.006) lower (range 15.5–26.7%) in the 65- to 78- than in the 45- to 54-yr-old men and women. When strength was adjusted for FFM or MM, the age-related differences were not significant in all muscle groups except the knee extensors tested at 240 degrees/s. Absolute strength of the women ranged from 42.2 to 62.8% that of men. When strength was expressed per kilogram of MM, these gender differences were smaller and/or not present. These data suggest that MM is a major determinant of the age- and gender-related differences in skeletal muscle strength. Furthermore, this finding is, to a large extent, independent of muscle location (upper vs. lower extremities) and function (extension vs. flexion).
Effects of BAY K 8644, nifedipine, and low Ca2+ on halothane and caffeine potentiation
Authors: Williams J. H. , Holland M. , Lee J. C. , Ward C. W. , Davy K. P.
Published: December 2017

The purpose of this investigation was to examine the effects of the Ca2+ agonist BAY K 8644 and the Ca2+ antagonist nifedipine on halothane- and caffeine-induced twitch potentiation of mammalian skeletal muscle. Muscle fiber bundles were taken from normal Landrace pigs and exposed to BAY K 8644 (10 microM), nifedipine (1 microM), and low Ca2+ media administered alone and in combination with halothane (3%) or with increasing concentrations of caffeine (0.5–8.0 mM). Both BAY K 8644 and halothane potentiated twitches by approximately 80%; when they were administered in combination, twitch potentiation was nearly double that caused by either drug alone. In the presence of nifedipine, halothane increased twitches by less than 30%. Low Ca2+ significantly depressed twitches by approximately 25% but also inhibited halothane's inotropic effect. BAY K 8644 augmented caffeine potentiation but only at low caffeine concentrations (0.5–2.0 mM). Nifedipine and low Ca2+ failed to inhibit caffeine's inotropic effects. These results suggest that halothane potentiates twitches via a mechanism that involves or is influenced by extracellular Ca2+.
Effects of maternal exercise on liver and skeletal muscle glycogen storage in pregnant rats
Authors: Mottola M. F. , Christopher P. D.
Published: December 2017

To examine the effects of maternal exercise on liver and skeletal muscle glycogen storage, female Sprague-Dawley rats were randomly divided into control, nonpregnant runner, pregnant nonrunning control, pregnant runner, and prepregnant exercised control groups. The exercise consisted of treadmill running at 30 m/min on a 10 degree incline for 60 min, 5 days/wk. Pregnancy alone, on day 20 of gestation, decreased maternal liver glycogen content and increased red and white gastrocnemius muscle glycogen storage above control values (P less than 0.05). In contrast, exercise in nonpregnant animals augmented liver glycogen storage and also increased red and white gastrocnemius glycogen content (P less than 0.05). By combining exercise and pregnancy, the decrease in liver glycogen storage in the pregnant nonexercised condition was prevented in the pregnant runner group and more glycogen was stored in both the red and white portions of the gastrocnemius than all other groups (P less than 0.05). Fetal body weight was greatest (P less than 0.05) in the pregnant runner group and lowest (P less than 0.05) in the prepregnant exercise control group. These results demonstrate that chronic maternal exercise may change maternal glycogen storage patterns in the liver and skeletal muscle with some alteration in fetal outcome.
Multiple-breath washout experiments in rat lungs
Authors: Verbanck S. , Gonzalez Mangado N. , Peces-Barba G. , Paiva M.
Published: December 2017

Multiple-breath washouts were performed on 30 Wistar rats postmortem in a study in which breaths of 90% O2–5% He-5% SF6 were given. Preliminary comparison of alveolar plateau slopes obtained from anesthetized rats in vivo and postmortem showed that ventilation distribution remains the same within 1 h after the animals were killed. For maneuvers with different preinspiratory lung volumes and end-inspiratory breathholding, we computed the normalized N2 slope (Sn) and Fowler and Bohr dead spaces [VDF(n) and VDB(n), respectively] as a function of breath number (n). For all maneuvers analyzed, Sn of all gases increased in the first two or three breaths and reached a horizontal asymptote thereafter. The value of Sn decreased, both with increasing preinspiratory lung volume and breath hold of 4 s. The fact that the horizontal Sn asymptote is reached after only two or three breaths suggests the absence of convection-dependent inhomogeneities (CDI) in rat lungs. This contrasts with multiple-breath washout experiments in humans, where interregional (gravity-dependent CDI) and intraregional CDI generate a marked increase in Sn throughout the entire washout. Also, in contrast with results in humans, VDF and VDB were independent of n. The present work suggests that rats may be used to study diffusion- and convection-dependent inhomogeneities without the influence of CDI or gas exchange.
Pulmonary function in men after oxygen breathing at 3.0 ATA for 3.5 h
Authors: Clark J. M. , Jackson R. M. , Lambertsen C. J. , Gelfand R. , Hiller W. D. , Unger M.
Published: December 2017

As a pulmonary component of Predictive Studies V, designed to determine O2 tolerance of multiple organs and systems in humans at 3.0–1.5 ATA, pulmonary function was evaluated at 1.0 ATA in 13 healthy men before and after O2 exposure at 3.0 ATA for 3.5 h. Measurements included flow-volume loops, spirometry, and airway resistance (Raw) (n = 12); CO diffusing capacity (n = 11); closing volumes (n = 6); and air vs. HeO2 forced vital capacity maneuvers (n = 5). Chest discomfort, cough, and dyspnea were experienced during exposure in mild degree by most subjects. Mean forced expiratory volume in 1 s (FEV1) and forced expiratory flow at 25–75% of vital capacity (FEF25–75) were significantly reduced postexposure by 5.9 and 11.8%, respectively, whereas forced vital capacity was not significantly changed. The average difference in maximum midexpiratory flow rates at 50% vital capacity on air and HeO2 was significantly reduced postexposure by 18%. Raw and CO diffusing capacity were not changed postexposure. The relatively large change in FEF25–75 compared with FEV1, the reduction in density dependence of flow, and the normal Raw postexposure are all consistent with flow limitation in peripheral airways as a major cause of the observed reduction in expiratory flow. Postexposure pulmonary function changes in one subject who convulsed at 3.0 h of exposure are compared with corresponding average changes in 12 subjects who did not convulse.
Site of action of calcium channel blockers in inhibiting endogenous pyrogen fever in rats
Authors: Stitt J. T. , Shimada S. G.
Published: December 2017

We have demonstrated that the Ca2+ channel blocker verapamil, administered intravenously, exerts an antipyretic effect on the febrile responses of rats to intravenously injected endogenous pyrogen (EP). We have also shown that the same intravenous dose of verapamil is ineffective in blocking fevers induced by the microinjection of exogenous prostaglandin E (PGE) into the organum vasculosum laminae terminalis (OVLT) of rats. Experiments were conducted to determine whether the site of this verapamil antipyresis was in the OVLT itself. The febrile responses of six male Sprague-Dawley rats to EP were determined at thermoneutrality. Verapamil (10 micrograms/rat) was microinjected directly into the OVLT, and the febrile responses to the EP dose were redetermined 15–30 min later. In every case the EP fevers were attenuated after verapamil pretreatment. Intra-OVLT injections of verapamil alone were without effect on body temperature. When the same dose of verapamil was injected into the OVLT 15 min before the injection of PGE into the same site, it had no effect on the ensuing PGE-induced fever. In view of the fact that less than 1/250th of the effective systemic dose of verapamil, when injected into the OVLT, was equally effective in blocking the EP fevers, we conclude that verapamil acts within the OVLT to block fever rather than peripherally. Furthermore, because verapamil administered into the OVLT does not block PGE fevers, it is unlikely that PGE produces fever by acting as a Ca2+ ionophore on hypothalamic neurons.
Oxygen radical mechanisms of brain injury following ischemia and reperfusion
Authors: Traystman R. J. , Kirsch J. R. , Koehler R. C.
Published: December 2017

This review addresses current understanding of oxygen radical mechanisms as they relate to the brain during ischemia and reperfusion. The mechanism for radical production remains speculative in large part because of the difficulty of measuring radical species in vivo. Breakdown of lipid membranes during ischemia leads to accumulation of free fatty acids. Decreased energy stores during ischemia result in the accumulation of adenine nucleotides. During reperfusion, metabolism of free fatty acids via the cyclooxygenase pathway and metabolism of adenine nucleotides via the xanthine oxidase pathway are the most likely sources of oxygen radicals. Although leukocytes have been found to accumulate in some models of ischemia and reperfusion, their mechanistic role remains in question. Therapeutic strategies aimed at decreasing brain injury have included administration of radical scavengers at the time of reperfusion. Efficacy of traditional oxygen radical scavengers such as superoxide dismutase and catalase may be limited by their inability to cross the blood-brain barrier. Lipid-soluble antioxidants appear more efficacious because of their ability to cross the blood-brain barrier and because of their presence in membrane structures where peroxidative reactions can be halted.
Effect of oxygenation on breath-by-breath response of the genioglossus muscle during occlusion
Authors: Gauda E. B. , Carroll J. L. , McColley S. , Smith P. L.
Published: December 2017

We investigated the effect of different levels of O2 tension (hypoxia, normoxia, and hyperoxia) on the breath-by-breath onset and peak electromyographic (EMG) activity of the genioglossus (GG) muscle during a five-breath end-expiratory tracheal occlusion of 20- to 30-s duration. GG and diaphragmatic (DIA) EMG activity were measured with needle electrodes in eight anesthetized tracheotomized adult cats. In response to occlusion, the increase in the number of animals with GG EMG activity was different during hypoxia, normoxia, and hyperoxia (P = 0.003, Friedman). During hypoxia, eight of eight of the animals had GG EMG activity by the third occluded effort. In contrast, during normoxia, only four of eight and, during hyperoxia, only three of eight animals had GG EMG activity throughout the entire five-breath occlusion. Similarly, at release of the occlusion, more animals had persistent GG EMG activity on the postocclusion breaths during hypoxia than during normoxia or hyperoxia. Breath-by-breath augmentation of peak amplitude of the GG and DIA EMGs on each occluded effort was accentuated during hypoxia (P less than 0.01) and abolished during hyperoxia (P = 0.10). These results suggest that hypoxemia is a major determinant of the rapidity of onset, magnitude, and sustained activity of upper airway muscles during airway occlusion.
Plasma catecholamine and lactate response during graded exercise with varied glycogen conditions
Authors: Podolin D. A. , Munger P. A. , Mazzeo R. S.
Published: December 2017

The relationships between the lactate threshold (TLa), plasma catecholamines, and ventilatory threshold (TVE) were examined under normal and glycogen-depleted conditions. Nine male subjects performed a graded exercise test on a bicycle ergometer in a normal glycogen (NG) state and in a glycogen-depleted (GD) state to determine if manipulation of muscle glycogen content would affect their ventilatory, lactate, and catecholamine responses. High correlations were found between plasma lactate and the two catecholamines, epinephrine (r = 0.964) and norepinephrine (r = 0.965) under both conditions. The GD protocol resulted in a shift in the TLa to a later work rate; inflections in epinephrine and norepinephrine shifted in a coordinated manner. TVE and TLa occurred at similar work loads under NG conditions [67.2 +/- 1.5 and 65.6 +/- 2.3% maximal oxygen consumption (VO2max), respectively], but TLa occurred at a later work load (75.3 +/- 1.9% VO2max) compared with TVE (68.3 +/- 1.6% VO2max) under GD conditions. These results suggest a causal relationship between plasma lactate and epinephrine during a graded exercise test under the glycogen conditions studied. Although an association existed between ventilation and lactate, this relationship was not as strong.
Interfacial transfer kinetics of NO2 into pulmonary epithelial lining fluid
Authors: Postlethwait E. M. , Langford S. D. , Bidani A.
Published: December 2017

Previous studies, both in intact lungs and epithelial lining fluid (ELF) (J. Appl. Physiol. 68: 594–603, 1990 and J. Appl: Physiol. 69: 523–531, 1990), have suggested that the steady-state absorption of inhaled NO2 is mediated by chemical reaction(s) between NO2 and ELF solute reactants. To characterize the kinetics of NO2 absorption into aqueous biological substrates across a gas-liquid interface, we utilized a closed system of known geometry and initial gas phase [NO2] [([NO2]g)0] to expose ELF (as bronchoalveolar lavage; BAL) and a biochemical model system (glutathione, GSH). Assessments of NO2 reactive uptake, into both GSH and ELF, indicated first-order NO2 kinetics [([NO2]g)0 less than or equal to 10.5 ppm] with effective rate constants of (kNO2)GSH = 4.8 and (kNO2)BAL = 2.9 ml.min-1.cm-2 (stirred). Above 10.5 ppm (1 mM GSH), zero-order kinetics were observed. Both (kNO2)GSH and (kNO2)BAL showed aqueous reactant dependence. The reaction order with respect to GSH and BAL was 0.47 and 0.64, respectively. We found no effect of interfacial surface area or bulk phase volume on kNO2. In unstirred systems, significant interfacial resistance was observed and was related to reactant concentration. These results indicate that NO2 reactive uptake follows first-order kinetics with respect to NO2 ([NO2]g less than or equal to 10.5 ppm) and displays aqueous substrate dependence. Furthermore the site of reactive absorption appears to be limited to near the aqueous surface interface. Unstirred conditions confine interfacial mass transfer kinetics in a dose-dependent manner. These phenomenological coefficients may provide the basis for direct extrapolation to environmentally relevant exposure concentrations.
Circadian rhythm in airway responsiveness and airway tone in patients with mild asthma
Authors: Bonnet R. , Jorres R. , Heitmann U. , Magnussen H.
Published: December 2017

To determine the characteristics and reproducibility of circadian rhythms of airway responsiveness to histamine and methacholine and their relationship to airway tone in patients with mild asthma, we studied nine subjects with complaints of nighttime awakening due to dyspnea and/or cough at least once a week. Their mean age was 31.4 yr (range 17–65) and their mean daytime FEV1 was 99 +/- 14 (SD) % predicted. Forced expiratory volume in 1 s (FEV1) and the provocative concentrations of histamine and methacholine necessary to decrease FEV1 by 20% (PC20FEV1) were determined every 4 h for 13 consecutive measurements. Three subjects were measured with histamine, three with methacholine, and three with both histamine and methacholine. Data were evaluated on an individual basis. PC20FEV1 to histamine and methacholine showed significant and reproducible circadian variations in all cases (P less than 0.01 each) with a mean amplitude of 1.00 +/- 0.17 (SD) doubling concentrations for histamine and 1.35 +/- 0.29 doubling concentrations for methacholine. The amplitude of PC20FEV1 was significantly larger (P less than 0.05) and the time of maximum responsiveness was significantly earlier (P less than 0.05) with methacholine compared with histamine. FEV1 showed significant (P less than 0.05) circadian variations in three of nine subjects, and peak expiratory flow rate showed variations in two subjects. Correlation between the variations of FEV1 and PC20FEV1 was significant (P less than 0.05) in 5 of 12 cases.(ABSTRACT TRUNCATED AT 250 WORDS)
Organ blood flow in Fischer-344 rats bearing MCA-induced sarcoma
Authors: Van Leeuwen P. A. , Bading J. R. , Vydelingum N. A. , Younes R. N. , de Rooij P. , Brennan M. F.
Published: December 2017

Although blood flow is central to systemic metabolism, little is known about the effect of tumor on the perfusion of host tissues. This study evaluated the effects of a methylcholanthrene-induced sarcoma on blood flow to intra-abdominal organs and skeletal muscle of Fischer-344 rats anesthetized with pentobarbital sodium. Animals were studied by aortic injection of radiolabeled microspheres when the tumors reached 20% of body weight. Total-organ arterial flows in spleen, liver, small intestine, and pancreas were each increased to 50–150% in tumor bearers relative to controls (P less than 0.05). Portal venous flow and flow per gram to hindlimb muscle were 60 +/- 20 and 300 +/- 100% greater, respectively, in tumor-bearing animals (P less than 0.005). This study shows that tumor growth can be associated with large changes in organ flow and distribution of cardiac output. The increase in skeletal muscle flow in the tumor bearers, which lost normal tissue weight relative to pair-fed controls (P less than 0.05), is in marked contrast to decreased muscle flow previously observed in simple starvation.
Erythrocyte insufflation-induced protection against oxygen toxicity: role of cytokines
Authors: Tsan M. F. , Lawrence D. , White J. E.
Published: December 2017

We studied the pulmonary response of adult rats to erythrocyte (RBC) and RBC lysate insufflation to define the mechanism of RBC insufflation-induced protection against oxygen toxicity. Tracheal insufflation of 1 ml RBC (75%) or RBC lysate induced an intense pulmonary inflammatory response. Within 24 h of oxygen exposure, greater than 95% of insufflated RBCs was hemolyzed. The cell-free fraction of alveolar lavage fluids from RBC- or RBC lysate-insufflated rats had similar capacity in protecting endothelial cells against H2O2 cytotoxicity. However, RBC insufflation but not RBC lysate insufflation, protected rats against oxygen toxicity. There was marked erythrophagocytosis by alveolar macrophages of RBC-insufflated rats. Insufflation of RBCs, but not RBC lysate, resulted in production of tumor necrosis factor and interleukin 1, which could be recovered by bronchoalveolar lavages. When rats were insufflated with a combination of RBC lysate and cytokines at dosages within the range of cytokine levels achievable in alveolar lavage fluids by RBC insufflation, they became tolerant to oxygen. These results suggest that endogenously produced tumor necrosis factor and interleukin-1 as a result of RBC insufflation may play an important role in RBC insufflation-induced oxygen tolerance.
Exercise training depletes sarcoplasmic reticulum calcium in coronary smooth muscle
Authors: Stehno-Bittel L. , Laughlin M. H. , Sturek M.
Published: December 2017

We examined the effects of chronic exercise training on sarcoplasmic reticulum (SR) Ca uptake, spontaneous SR Ca release, and whole-cell currents in coronary smooth muscle cells. Single coronary artery smooth muscle cells demonstrated increases in intracellular free Ca (Cai) during depolarization (measured with fura-2) that were abolished by diltiazem (10(-4) M). Diltiazem significantly inhibited (80%) refilling of the SR Ca store. The SR Ca store of exercise-trained pigs was 64% less after 11 min vs. 2 min of recovery, whereas cells from sedentary pigs showed no depletion. Exercise-training-induced depletion of the SR Ca store was abolished when ryanodine (10(-5) M) was applied during the recovery, but depletion was enhanced by low concentrations of ryanodine (10(-8) M). In smooth muscle from sedentary pigs, 10(-8) M ryanodine mimicked the effects of exercise training by depleting the SR Ca store during 11 min of recovery (54% depletion). When allowed a longer recovery without ryanodine (14 min or without prior depolarization), the SR Ca store in cells from exercise-trained pigs returned toward peak levels. The outward K current vs. voltage relationship did not differ in cells from exercise-trained or sedentary pigs. Exercise training reduced the number of spontaneous transient outward currents normally found in cells from sedentary pigs. We introduce a model that provides a rational basis to explain the results obtained in this study.
Occlusion pressure response to inspiratory flow-resistive loading in anesthetized swine
Authors: Segal B. S. , Inman J. G. , Moss I. R.
Published: December 2017

We examined the effects of chronic exercise training on sarcoplasmic reticulum (SR) Ca uptake, spontaneous SR Ca release, and whole-cell currents in coronary smooth muscle cells. Single coronary artery smooth muscle cells demonstrated increases in intracellular free Ca (Cai) during depolarization (measured with fura-2) that were abolished by diltiazem (10(-4) M). Diltiazem significantly inhibited (80%) refilling of the SR Ca store. The SR Ca store of exercise-trained pigs was 64% less after 11 min vs. 2 min of recovery, whereas cells from sedentary pigs showed no depletion. Exercise-training-induced depletion of the SR Ca store was abolished when ryanodine (10(-5) M) was applied during the recovery, but depletion was enhanced by low concentrations of ryanodine (10(-8) M). In smooth muscle from sedentary pigs, 10(-8) M ryanodine mimicked the effects of exercise training by depleting the SR Ca store during 11 min of recovery (54% depletion). When allowed a longer recovery without ryanodine (14 min or without prior depolarization), the SR Ca store in cells from exercise-trained pigs returned toward peak levels. The outward K current vs. voltage relationship did not differ in cells from exercise-trained or sedentary pigs. Exercise training reduced the number of spontaneous transient outward currents normally found in cells from sedentary pigs. We introduce a model that provides a rational basis to explain the results obtained in this study.
Effects of environmental temperature on the venodilatory response to nitroglycerin
Authors: Gascho J. A. , Gehman D. , Brandt R.
Published: December 2017

The venodilatory response to nitroglycerin (0.8 mg sublingually) was measured in 10 healthy young male volunteers in a cool [24.3 +/- 0.6 degrees C skin temperature (Tsk)] and a warm environment (34.7 +/- 0.2 degrees C Tsk). Nitroglycerin caused mean arterial pressure to fall and heart rate to rise in both the cool (105 +/- 2 to 96 +/- 3 mmHg; 55 +/- 3 to 62 +/- 3 beats/min) and the warm environment (87 +/- 3 to 81 +/- 3 mmHg; 66 +/- 4 to 75 +/- 3 beats/min), but the fall in pressure was greater in the cool than in the warm environment. Forearm blood flow was reduced and forearm vascular resistance elevated in the cool (117 +/- 19 units; 1.15 +/- 0.08 ml.100 cc arm-1.min-1) compared with the warm environment (15 +/- 3 units; 8.60 +/- 1.89 ml.100 cc arm-1.min-1). Nitroglycerin caused forearm vascular resistance to fall in the cool but had no effect in the warm environment. Venous distensibility (increase in venous volume per 30-mmHg increase in venous pressure) was twice as great in the warm as in the cool environment (3.90 +/- 0.27 vs. 1.88 +/- 0.23 ml/100 cc arm). However, the venodilatory effect of nitroglycerin was similar in the cool and warm environments (0.79 +/- 0.10 vs. 0.67 +/- 0.13 ml/100 cc arm, respectively). Arterioles are not dilated by nitroglycerin in the warmer environment, but the venodilatory effect of nitroglycerin is quantitatively similar in the two environments.
Functional antagonism of airway constriction in the canine lung periphery
Authors: Lindeman K. S. , Hirshman C. A. , Freed A. N.
Published: December 2017

We studied the ability of a beta-adrenergic agonist (albuterol) to attenuate calcium chelator- and acetylcholine-induced airway constriction in the lung periphery of anesthetized mongrel and Basenji-Greyhound (BG) dogs. A wedged bronchoscope technique was used to measure collateral system resistance before and after challenges with aerosolized Na2EDTA and acetylcholine. Time course of the response to Na2EDTA differed significantly between mongrel and BG dogs. Peak response to challenge with 4% Na2EDTA occurred within 2 min for mongrel dogs and at 5 min for BG dogs. Albuterol (1 microgram/kg iv) significantly attenuated Na2EDTA-induced bronchoconstriction in both groups of animals (P less than 0.01, each group). Albuterol (1 microgram/kg iv) significantly attenuated acetylcholine-induced bronchoconstriction in mongrel (P less than 0.01) but not in BG dogs. We conclude that a qualitative difference exists in the mechanism of Na2EDTA-induced constriction in the lung periphery of BG compared with mongrel dogs. In addition, the lung periphery of BG dogs demonstrates reduced beta-adrenergic sensitivity with respect to a cholinergic challenge compared with mongrels, suggesting enhanced cholinergic inhibition of the beta-adrenergic system.
Segmental barrier properties of the pulmonary microvascular bed
Authors: Qiao R. L. , Bhattacharya J.
Published: December 2017

We determined liquid flux across single pulmonary microvessels of dog, ferret, and rat by our split-drop technique (J. Appl. Physiol. 64: 2562–2567, 1988). Data are reported from 58 lungs excised under halothane or pentobarbital sodium anesthesia and then blood perfused. We stopped blood flow at known vascular pressures and then micropunctured microvessels to inject oil, which we split with albumin solution. From measurements of vessel diameter and split oil drop length, we calculated Jv, the liquid transport rate per unit surface area [x 10(-6) ml/(cm2.s)]. At constant vascular pressure, Jv was not significantly different after different periods of oil-endothelium contact and at different sites within a single vessel. From measurements of Jv at different vascular pressures, we determined Lp, the hydraulic conductivity [x 10(-7) ml/(cm2.s.cmH2O)], and Pzf, the zero filtration pressure. From determinations of Pzf at different albumin concentrations, we quantified sigma alb, the albumin reflection coefficient. Lp and Pzf did not differ among venules of the same lung. However, in venules, Lp was 40% higher and sigma alb 25% lower than in arterioles (P less than 0.01). We conclude that 1) micropuncture procedures incidental to our split-drop technique do not progressively deteriorate the experimental microvessel and 2) in lung, permeability is higher in venules than in arterioles.
Effects of blood flow on lung ACE kinetics: evidence for microvascular recruitment
Authors: Toivonen H. J. , Catravas J. D.
Published: December 2017

The parameter Amax/Km (product of reactant enzyme mass in perfused microvessels and the constant kcat/Km), calculated from in vivo assays of pulmonary endothelial ectoenzymes (e.g., angiotensin-converting enzyme, ACE), can provide estimates of the perfused pulmonary microvascular surface area (PMSA) in the absence of enzyme dysfunction. We examined the relationship between PMSA and pulmonary blood flow (Qb) in anesthetized rabbits placed on total heart bypass, using [3H]benzoyl-Phe-Ala-Pro (BPAP) as the ACE substrate. When Qb was increased from 250 to 1,100 ml/min, at zone 3 conditions, pulmonary arterial pressure increased, pulmonary vascular resistance (PVR) decreased, and Amax/Km increased linearly, reflecting increasing PMSA. When only the left lung was perfused, increasing Qb from 250 to 636 +/- 17 ml/min (the last value representing fully recruited and/or distended vascular bed), PVR decreased, while Amax/Km increased. When Qb was further increased to 791 +/- 44 ml/min, both PVR and Amax/Km remained unchanged, confirming the lack of additional changes in PMSA. We conclude that Amax/Km provides a sensitive indication of PMSA, because it 1) increases with increasing Qb and decreasing PVR, 2) reaches a maximum at Qb values that correspond to the minimal values in PVR, and 3) like PVR, did not change with further increases in Qb. Compared with predicted changes in PMSA produced by either microvascular recruitment alone or distension alone, our data indicate that recruitment is a larger contributor to the observed increase in PMSA.
Role of phospholipid lining on respiratory mucus clearance by cough
Authors: Girod S. , Galabert C. , Pierrot D. , Boissonnade M. M. , Zahm J. M. , Baszkin A. , Puchelle E.
Published: December 2017

Phospholipid lining, present at the respiratory mucus-mucosa interface, may have an important role in the protective function of the airways by its abhesive properties and may also facilitate mucus transport. To mimic respiratory mucus-mucosa interface, monolayers of three different forms of phosphatidylglycerol (PG) have been deposited on glass slides by the Langmuir-Blodgett technique. Mucus adhesion and clearance by cough of mucus on these PG-coated or noncoated surfaces have been analyzed and compared, using frog respiratory mucus as “normal” mucus. Among the three PG types studied, the phosphatidylglycerol distearoyl, which is the phospholipid with the longest saturated fatty acid chain, was found to significantly improve the mucus cough clearance by decreasing the mucus work of adhesion compared with the noncoated surfaces. On the other hand, phosphatidylglycerol dipalmitoyl did not improve mucus cough clearance although it decreased mucus adhesion, and phosphatidylglycerol dioleyl did not improve either mucus cough clearance or mucus adhesion.
Role of caudal ventrolateral medulla in reflex and central control of airway caliber
Authors: Padrid P. A. , Haselton J. R. , Kaufman M. P.
Published: December 2017

We investigated the role played by the caudal ventrolateral (CVL) medulla in the reflex and central neural control of airway caliber in chloralose-anesthetized dogs. Changes in total lung resistance were evoked by four different stimuli. These changes were compared before and after bilateral injection of either ibotenic acid (75 nl; 100 mM) or cobalt chloride (75 nl; 50 mM) into the CVL medulla. The four stimuli used to change lung resistance were static muscular contraction, electrical stimulation of thin fiber afferents in the sciatic nerve, electrical stimulation of the posterior diencephalon, and hypoxia. The first three stimuli have been shown to decrease total lung resistance, whereas the latter stimulus has been shown to increase resistance. We found that injection of both ibotenic acid, which destroys cell bodies but not fibers of passage, and cobalt, which prevents synaptic transmission, either abolished or greatly attenuated the decrease in total lung resistance evoked by static contraction, by sciatic nerve stimulation, and by posterior diencephalic stimulation. We also found that injection of ibotenic acid and cobalt attenuated the reflex increase in lung resistance evoked by hypoxia. In control experiments, we found that bilateral injection of ibotenic acid into the dorsal medulla had no effect on the changes in total lung resistance evoked by these four stimuli. We conclude that the CVL medulla plays an important role in the reflex and central control of airway caliber.
Exercise training and responsiveness of isolated coronary arteries
Authors: Rogers P. J. , Miller T. D. , Bauer B. A. , Brum J. M. , Bove A. A. , Vanhoutte P. M.
Published: December 2017

Exercise is associated with release of catecholamines and vasoactive intestinal polypeptides. Recurrent exposure to catecholamines modifies the sensitivity of adrenoceptors. To test the hypothesis that exercise training may affect the sensitivity of the epicardial coronary arteries, we performed studies on isolated coronary arteries from male dogs capable of running on a treadmill. The animals were separated randomly into two groups: sedentary and exercise training. After 11 wk, rings of left circumflex and left anterior descending coronary arteries were studied in vitro. Contractions to alpha 1-adrenergic agonists (norepinephrine and phenylephrine) were not affected by exercise training. During contractions with prostaglandin F2 alpha, endothelium-dependent relaxations to alpha 2-adrenergic agonists (norepinephrine and UK 14304) were not reduced significantly by exercise training. The concentration-relaxation curves to beta-adrenergic agonists (norepinephrine, isoproterenol, and epinephrine) were shifted to the right after training. The concentration-response curves to vasoactive intestinal polypeptide, but not that to substance P, were shifted to the right in rings with endothelium from exercise-trained animals. These findings demonstrate a decrease in responsiveness of canine vascular smooth muscle to beta-adrenergic agonists and to vasoactive intestinal polypeptide after exercise training.
Effects of upper airway pressure on abdominal muscle activity in conscious dogs
Authors: Plowman L. , Lauff D. C. , McNamara F. , Berthon-Jones M. , Sullivan C. E.
Published: December 2017

We have examined arousal and abdominal muscle electromyogram (EMGabd) responses to upper airway pressure stimuli during physiological sleep in four dogs with permanent side-hole tracheal stomata. The dogs were trained to sleep with a tightly fitting snout mask, hermetically sealed in place, while breathing through a cuffed endotracheal tube inserted through the tracheostomy. Sleep stage was determined by behavioral and electroencephalographic criteria. EMGabd activity was measured using bipolar fine-wire electrodes inserted into the abdominal muscle layers. Static increases or decreases in upper airway pressure (+/- 6 cmH2O), when applied at the snout mask or larynx (upper trachea), caused an immediate decrease in EMGabd on the first two to three breaths; EMGabd usually returned to control levels within the 1-min test interval. In contrast, oscillatory pressure waves at 30 Hz and +/- 3 cmH2O amplitude (or -2 to -8 cmH2O amplitude) produced an immediate and sustained reduction in IMGabd in all sleep states. Inhibition of EMGabd could be maintained over many minutes when the oscillatory pressure stimulus was pulsed by using a cycle of 0.5 s on and 0.5 s off. Oscillatory upper airway pressures were also found to be powerful arousal-promoting stimuli, producing arousal in 94% of tests in drowsiness and 66% of tests in slowwave sleep. The results demonstrate the presence of breath-by-breath upper airway control of abdominal muscle activity.
Factors affecting the accuracy of esophageal balloon measurement of pleural pressure in dogs
Authors: Dechman G. , Sato J. , Bates J. H.
Published: December 2017

Simultaneous measurement of esophageal and tracheal pressures during an occluded inspiratory effort was used to assess the accuracy of the esophageal balloon for measuring pleural pressure in dogs. Esophageal balloons were inserted in five mongrel dogs, and an occlusion test was performed with the balloon tip 5, 10, 15, 20, and 25 cm above the esophageal sphincter; at lung volumes of functional residual capacity (FRC) and FRC + 600 ml; and in supine and right- and left-side lying postures. The protocol was repeated in paralyzed animals. This time the occlusion test was performed by injecting air into a plethysmograph to change the body surface pressure, simulating pressure changes produced by respiratory efforts in spontaneously breathing animals. In 47% of the tests in spontaneously breathing dogs, the slope of esophageal vs. tracheal pressure varied greater than 10% from unity. After paralysis the slope did not vary greater than 5% from unity under any circumstance. These data indicate that the poorer performance of the occlusion test in nonparalyzed dogs is due to active tension in the walls of the esophagus and stress induced in the intrathoracic soft tissues by the descent of the diaphragm during a breathing effort.
Hyperbaric oxygen toxicity: role of thromboxane
Authors: Jacobson J. M. , Michael J. R. , Meyers R. A. , Bradley M. B. , Sciuto A. M. , Gurtner G. H.
Published: December 2017

Exposing rabbits for 1 h to 100% O2 at 4 atm barometric pressure markedly increases the concentration of thromboxane B2 in alveolar lavage fluid [1,809 +/- 92 vs. 99 +/- 24 (SE) pg/ml, P less than 0.001], pulmonary arterial pressure (110 +/- 17 vs. 10 +/- 1 mmHg, P less than 0.001), lung weight gain (14.6 +/- 3.7 vs. 0.6 +/- 0.4 g/20 min, P less than 0.01), and transfer rates for aerosolized 99mTc-labeled diethylenetriamine pentaacetate (500 mol wt; 40 +/- 14 vs. 3 +/- 1 x 10(-3)/min, P less than 0.01) and fluorescein isothiocyanate-labeled dextran (7,000 mol wt; 10 +/- 3 vs. 1 +/- 1 x 10(-4)/min, P less than 0.01). Pretreatment with the antioxidant butylated hydroxyanisole (BHA) entirely prevents the pulmonary hypertension and lung injury. In addition, BHA blocks the increase in alveolar thromboxane B2 caused by hyperbaric O2 (10 and 45 pg/ml lavage fluid, n = 2). Combined therapy with polyethylene glycol- (PEG) conjugated superoxide dismutase (SOD) and PEG-catalase also completely eliminates the pulmonary hypertension, pulmonary edema, and increase in transfer rate for the aerosolized compounds. In contrast, combined treatment with unconjugated SOD and catalase does not reduce the pulmonary damage. Because of the striking increase in pulmonary arterial pressure to greater than 100 mmHg, we tested the hypothesis that thromboxane causes the hypertension and thus contributes to the lung injury. Indomethacin and UK 37,248–01 (4-[2-(1H-imidazol-1-yl)-ethoxy]benzoic acid hydrochloride, an inhibitor of thromboxane synthase, completely eliminate the pulmonary hypertension and edema.(ABSTRACT TRUNCATED AT 250 WORDS)
Volume infusion produces abdominal distension, lung compression, and chest wall stiffening in pigs
Authors: Mutoh T. , Lamm W. J. , Embree L. J. , Hildebrandt J. , Albert R. K.
Published: December 2017

The effect of severe generalized edema on respiratory system mechanics is not well described. We measured airway pressure, gastric pressure, and four vertical pleural pressures in 13 anesthetized paralyzed pigs ventilated in the upright position. Pressure-volume relationships of the respiratory system, chest wall, and lung were measured on deflation from total lung capacity to residual volume and during tidal breathing both before (control) and 50 min after one of two interventions. In one series of experiments, a volume equal to 15–20% of the pig's body weight was infused intravenously. In a second series, a balloon was placed in the peritoneal space to distend the abdomen to the same gastric pressures as achieved in the first series. Measurements were compared before and after either abdominal balloon inflation or volume infusion. Volume infusion increased the pleural pressure in dependent lung regions, decreased both total lung capacity (34%) and functional residual capacity (62%) (both P less than 0.05), and markedly shifted the respiratory system and chest wall pressure-volume curves to the right, but it only moderately affected the lung deflation curve. Tidal compliances of the respiratory system, chest wall, and lung decreased 36, 31, and 49%, respectively (all P less than 0.05). The effect of abdominal balloon inflation on respiratory system mechanics was similar to that of volume infusion. We conclude that infusing large volumes of fluid markedly alters chest wall mechanics, mainly by causing abdominal distension that prohibits descent of the diaphragm.
Inflammation and oxygen free radical formation during pulmonary ischemia-reperfusion injury
Authors: Hamvas A. , Palazzo R. , Kaiser L. , Cooper J. , Shuman T. , Velazquez M. , Freeman B. , Schuster D. P.
Published: December 2017

In a companion study, we showed that 2 h of warm unilateral lung ischemia followed by reperfusion resulted in bilateral tissue injury, indicated by increases in extravascular density (EVD) and permeability, measured as the pulmonary transcapillary escape rate (PTCER) for radiolabeled transferrin. EVD and PTCER measurements were obtained with the quantitative imaging technique of positron emission tomography (PET). In the current study, we evaluated this increase in EVD histologically and correlated EVD and PTCER with measurements of oxidant-reactive sulfhydryls (RSH) in plasma as a marker of oxygen free radical (OFR) formation. Histologically edema, leukocyte infiltration, and hemorrhage were all present on the ischemic side, but only after reperfusion, whereas only neutrophil infiltration was observed on the nonischemic side. Histology scores correlated with EVD (r = 0.81) and PTCER (r = 0.75), but permeability was abnormal at times even in the absence of neutrophil infiltration. Plasma RSH concentration from the ischemic lung decreased significantly (P less than 0.05) during pulmonary ischemia (i.e., before reperfusion) and returned to baseline on reperfusion. The degree of RSH oxidation did not correlate with the severity of injury as measured by PET or histology. Thus pulmonary ischemia-reperfusion injury is characterized by inflammation, hemorrhage, edema, and OFR formation. Injury occurred after reperfusion, not after ischemia alone. In addition, injury to the contralateral nonischemic lung suggests a neutrophil-independent circulating mediator of injury.
Antagonistic interaction of laryngeal and central chemoreceptor respiratory reflexes
Authors: Van Vliet B. N. , Uenishi M.
Published: December 2017

Stimulation of laryngeal afferent fibers evokes a profound reflex inhibition of central respiratory drive. The interaction of this airway reflex with chemoreceptive ventilatory control mechanisms is poorly understood. The present study was undertaken to determine whether there is significant interaction between the effects of central chemoreceptor and laryngeal afferent stimulation on central inspiratory activity and, if so, to also determine the nature of the interaction. The effect of electrical stimulation of the superior laryngeal nerve (SLN) on the timing and intensity of central inspiratory activity was determined from the rectified and filtered phrenic neurogram in 10 dogs. Each dogs was decerebrated, artificially ventilated, vagotomized, and had the carotid bodies denervated. In each case, stimulation of the right SLN at 3 and 10 Hz caused a frequency-dependent slowing or arrest of central inspiratory activity. Increases in arterial PCO2 (PaCO2) attenuated the absolute level of inhibition of central inspiratory activity recorded during both SLN stimulation and control periods. Tp clarify the nature of the interaction between chemoreceptor and laryngeal afferent stimulation, the relationship between PaCO2 and central inspiratory activity was investigated during stimulation of the SLN at 0, 3, and 10 Hz. Control central inspiratory activity increased as a sigmoidal function of PaCO2. This sigmoidal relationship was greatly depressed during SLN stimulation but did not appear to be shifted along the PaCO2 axis. The results of this study therefore suggest that the interaction between central chemoreceptor and laryngeal afferent stimulation is multiplicative: the inhibition of the central inspiratory activity is mediated by an attenuation and not a resetting of central chemoreflexes.
Quantitative evaluation of pulmonary stretch receptor activity during high-frequency ventilation
Authors: Thompson-Gorman S. L. , Fitzgerald R. S. , Mitzner W.
Published: December 2017

The purpose of this study was to determine the neural output of pulmonary stretch receptors (PSRs) in response to conditions that, in previous studies (J. Appl. Physiol. 65: 179–186, 1988 and Respir. Physiol. 80: 307–322, 1990), produced apnea in anesthetized cats. These conditions included changes in airway pressure (Paw; 2 or 6 cmH2O), stroke or tidal volume (1–4 ml/kg), frequency [conventional mechanical ventilation (CMV) vs. high-frequency ventilation (HFV) at 10, 15, and 20 Hz], and levels of inspired CO2 (0, 2, and 5%). These data were needed to assess properly the specific contribution of the PSRs to the apnea found with certain combinations of the above variables. Each PSR was subjected to HFV over a range of mechanical and chemical settings, and its activity was recorded. PSRs exhibited continuous activity associated with pump stroke in 11 of 12 fibers tested. PSRs fired more rapidly when mean Paw was 6 cmH2O [45.3 +/- 0.8 (SE) impulses/s] than when it was 2 cmH2O (31.7 +/- 0.9 impulses/s, P = 0.0001). At both pressures, PSR activity increased as the volume of inflation, or tidal volume, was increased from 1 to 4 ml/kg. At Paw of 2 cmH2O, the number of impulses per second for HFV was not different from that for CMV (averaged over the respiratory cycle), under conditions previously demonstrated as apneogenic for both modes of ventilation. Therefore the absolute amount of information being sent to the brain stem processing centers via PSRs during HFV did not differ from that during CMV. Thus any PSR contribution to HFV-induced apnea must have been the result of changes in the pattern of the signal or the central nervous system's processing of it rather than an increase in the amount of inhibitory afferent signal.