bluuebunny/crossref_metadata_2025 huggingface dataset:
Maximal aerobic capacity at several ambient concentrations of CO at several altitudes
Authors: Horvath S. M. , Bedi J. F. , Wagner J. A. , Agnew J.
Published: December 2017

To assess the nature of the combined effect of the hypoxias of altitude (ALT) and CO exposure, 11 men and 12 women nonsmokers served as subjects in a double-blind experiment. The exposure conditions were four ambient CO levels (0, 50, 100, and 150 ppm) at each of four ALT (55, 1,524, 2,134, and 3,048 m). Each subject, after attaining the required ALT and ambient CO level, performed a maximal aerobic capacity test (VO2max). Blood samples were obtained before, at 50-W, 100-W, 150-W, and maximum work loads and at the 5th min of recovery. Blood were analyzed for hemoglobin, hematocrit, plasma proteins, lactates, and carboxyhemoglobin (HbCO). VO2max was similar at 55 and 1,524 m and decreased by 4 and 8% from the 55-m value at 2,134 and 3,048 m, respectively. On the basis of all statistical analyses, we concluded that VO2max values measured in men were only slightly diminished due to increased ambient CO. HbCO attained at maximum was highest at 55 m and lowest at 3,048 m. Women's HbCO concentrations were lower than men's. At maximal work loads CO shifted into extravascular spaces and returned to the vascular space within 5 min after exercise stopped. The independence of altitude and CO hypoxias on parameters of the maximum aerobic capacity test and a decrease in the CO to HbCO uptake with increasing altitude were demonstrated and attributed in part to the decrease in driving pressure of CO at altitude.
Lung aeration and lung water dynamics in artificially ventilated newborn lambs
Authors: Maloney J. E. , Kondo C. , Takahashi Y. , Dickson V. , Grant D. , Schoel W. M.
Published: December 2017

To the present lung liquid dynamics in the immediate neonatal period have been measured mainly by gravimetric techniques. This paper explores lung aeration and lung water dynamics in seven fetal lambs between 139 and 142 days of gestation delivered by caesarean section and ventilated on a constant-volume respirator. After caesarean section and instrumentation, fetal lambs were quickly transferred to a warm X-ray table and connected to a volume-cycled respirator. X-ray fluoroscopic images of the chest commenced before the first breath and were recorded on video tape. After 1 h of ventilation, measurements were made of pulmonary blood volume, and lung samples were taken for wet weight and dry weight analysis. Fluoroscopic image brightness was calibrated by comparison with images obtained from a water wedge, which extended across the X-ray field. Thus image brightness was related to "equivalent water path length" through the thorax. Within a defined lung field, image brightness increases as the amount of lung water in the path of the X-ray beam is reduced. This occurs rapidly at first and then more slowly over the remaining hour. There was considerable variation between the reduction of liquid in the lung fields examined within the one animal, as well as the absolute amount of fluid that had been cleared during the 1st h.
Oxygen radicals and antioxidant enzymes alter pulmonary vascular reactivity in the rat lung
Authors: Archer S. L. , Peterson D. , Nelson D. P. , DeMaster E. G. , Kelly B. , Eaton J. W. , Weir E. K.
Published: December 2017

It has been postulated that changes in the availability of partially reduced O2 species, such as O2 radicals, could serve as a link between PO2 in the alveolus and pulmonary vascular tone (Herz 11: 127–141, 1986). To assess this hypothesis, the hemodynamic effects of acute changes in the balance between the production of O2 radicals and availability of antioxidant enzymes were studied in the isolated perfused rat lung. Intravascular generation of O2 radicals, by administration of xanthine-xanthine oxidase, decreased the pulmonary vascular pressor response to alveolar hypoxia (-55 +/- 5%) and angiotensin II (-58 +/- 10%, P less than 0.01 for each) in isolated perfused rat lungs without increasing the lung wet-to-dry weight ratio. Decreases in pulmonary vascular reactivity were inhibited by pretreatment of the lung with desferrioxamine or a mixture of catalase and superoxide dismutase. Catalase and superoxide dismutase preserved the hypoxic pressor response whether given in liposomes or in dissolved form. Superoxide dismutase administered free in solution, or combined with catalase in liposomes, increased the normoxic pulmonary arterial pressure and enhanced vascular reactivity to angiotensin II and hypoxia. Lungs treated with antioxidant enzymes in liposomes had 50% higher lung catalase levels than control lungs (P less than 0.05). These findings demonstrate that exogenous partially reduced O2 species can decrease pulmonary vascular reactivity and suggest that endogenous radicals, superoxide radical in particular, might be important in modulating pulmonary vascular tone.
Cardiorespiratory and cellular changes with interleukin 2 infusion in sheep
Authors: Glauser F. L. , Bechard D. E. , DeBlois G. G. , Fowler A. A. , Merchant R. E. , Jesmok G. , Fairman R. P.
Published: December 2017

Recombinant interleukin 2 (rIL-2) administration, a new form of therapy for patients with far-advanced cancer, is associated with a "third space" syndrome, i.e., pulmonary edema, respiratory distress, and hypoxemia, which limits the dose and duration of treatment. To extend our knowledge regarding this toxicity, we established a sheep chronic lung lymph fistula model and measured hemodynamics, arterial blood gases, caudal mediastinal (lung) lymph flow (QL), and blood and lung lymph cellular changes before, during, and after (recovery) a 3-day continuous rIL-2 infusion (9 x 10(5) U/kg). Moderate systemic hypotension, mild pulmonary hypertension, and an increase in alveolar-arterial PO2 gradient was present on day 3 of rIL-2 infusion. QL increased from a base line of 1.9 +/- 0.2 to a maximum of 4.3 +/- 1.1 ml/15 min on day 3 of rIL-2 infusion. At no time was there a change in lymph-to-plasma protein ratio. The leukocyte count increased significantly to 16.1 +/- 4.5 x 10(3) cells/mm3 at recovery day 1. The percentage of blood lymphocytes decreased significantly by day 1 of rIL-2 infusion, returned to base-line levels on day 3, and significantly increased on day 2 of recovery. Lung lymph lymphocytes decreased significantly on days 1 and 2 of rIL-2 infusion. There was a shift in their size; i.e., their area increased from 32 +/- 7 to 57 +/- 19 micron 2 (P less than 0.05) by day 2 of rIL-2 infusion. By day 1 of recovery, lung lymph lymphocyte counts increased significantly.(ABSTRACT TRUNCATED AT 250 WORDS)
Bronchial responsiveness and inflammation in guinea pigs exposed to acrolein
Authors: Leikauf G. D. , Leming L. M. , O'Donnell J. R. , Doupnik C. A.
Published: December 2017

Bronchial hyperresponsiveness can be produced experimentally after inhalation of numerous nonimmunospecific stimuli; our objective was to determine whether acrolein, a component of cigarette smoke, could increase bronchial reactivity to intravenously administered acetylcholine in guinea pigs. Bronchial responsiveness was assessed twice before and 1, 2, 6, and 24 h after exposures to less than or equal to 0.01 (sham), 0.31, 0.67, 0.94, or 1.26 parts per million for 2 h (5–7 guinea pigs/group). To examine the possible relationships of responsiveness to inflammatory mediator release and cellular infiltration, bronchoalveolar lavage was performed in another 30 guinea pigs before (control) and 0, 1, 2, 6, or 24 h after exposures. Pulmonary resistance was increased immediately after exposure (5 min) and returned to control values within 30–60 min. Increased bronchial responsiveness was evident within 1 h and became maximal 2–4 h after exposure. The acetylcholine dose necessary to double resistance decreased from 104.2 +/- 7.3 to 79.6 +/- 15.9 at 1 h and was 32.5 +/- 7.9 at 2 h and 32.8 +/- 7.6 micrograms.kg-1 at 6 h. Increases in two eicosanoids, thromboxane B2 (from 167 +/- 21 to 314 +/- 77 pg/ml) and prostaglandin F2 alpha (from 98 +/- 20 to 285 +/- 62 pg/ml) occurred immediately after exposure, whereas an influx of neutrophils occurred 24 h later (from 2.2 +/- 1.2 to 11.3 +/- 3.6%). These temporal relationships suggest that neutrophil infiltration may be a sufficient but not a necessary condition for the onset of bronchial hyperresponsiveness and that injury to cells normally present in the lung are responsible for the mediators thought to influence bronchial responsiveness.
Oxidation of a glucose polymer during exercise: comparison with glucose and fructose
Authors: Massicotte D. , Peronnet F. , Brisson G. , Bakkouch K. , Hillaire-Marcel C.
Published: December 2017

The purpose of this study was to compare the oxidation of 13C-labeled glucose, fructose, and glucose polymer ingested (1.33 g.kg-1 in 19 ml.kg-1 water) during cycle exercise (120 min, 53 +/- 2% maximal O2 uptake) in six healthy male subjects. Oxidation of exogenous glucose and glucose polymer (72 +/- 15 and 65 +/- 18%, respectively, of the 98.9 +/- 4.7 g ingested) was similar and significantly greater than exogenous fructose oxidation (54 +/- 13%). A transient rise in plasma glucose concentration was observed with glucose ingestion only. However, plasma insulin levels were similar with glucose and glucose polymer ingestions and significantly higher than with water or fructose ingestion. Plasma free fatty acid and glycerol responses to exercise were blunted with carbohydrate ingestion. However, fat utilization was not significantly different with water (82 +/- 14 g), glucose (60 +/- 3 g), fructose (59 +/- 11 g), or glucose polymer ingestion (60 +/- 8 g). Endogenous carbohydrate utilization was significantly lower with glucose (184 +/- 22 g), glucose polymer (187 +/- 31 g), and fructose (211 +/- 18 g) than with water (239 +/- 30 g) ingestion. Plasma volume slightly increased with water ingestion (7.4 +/- 4.5%), but the decrease was similar with glucose (-7.6 +/- 5.1%) and glucose polymer (-8.2 +/- 4.6%), suggesting that the rate of water delivery to plasma was similar with the two carbohydrates.(ABSTRACT TRUNCATED AT 250 WORDS)
Distribution of bronchoconstrictor responses in isolated-perfused rat lung
Authors: Munoz N. M. , Chang S. W. , Murphy T. M. , Stimler-Gerard N. P. , Blake J. , Mack M. , Irvin C. , Voelkel N. F. , Leff A. R.
Published: December 2017

We studied the effects of bronchoconstrictor stimuli administered selectively through isolated-perfused preparations of the bronchial and pulmonary circulations of 80 Sprague-Dawley rats. Dose-related contraction was elicited with infusion of acetylcholine (ACh), histamine, and serotonin (5-HT). Bolus infusion of 10(-5) mol ACh caused a 3.5-fold increase in pulmonary resistance (RL) after infusion into the pulmonary circulation (PC) and a 2.5-fold increase in the bronchial circulation (BC) (P less than 0.05 vs. control) that was blocked selectively in each circulation with atropine. Administration of 10(-5) mol 5-HT into the BC caused only a 45% increase in RL; the same dose of 5-HT caused a 5.1-fold increase in RL in the PC. A biphasic (increase at lower doses/decrease at higher doses) change in RL was elicited by histamine that was converted to dose-related constriction after H2-receptor blockade with cimetidine in both BC and PC. Response to exogenous ACh remained viable for greater than 5 h. Infusion of the mast cell degranulating agent, compound 48/80 (48/80), caused increase in RL that corresponded to quantitative recovery of histamine in the perfusates of both BC and PC. Histamine concentration in the perfusate increased from 47.2 +/- 31.8 (base line) to 624 +/- 60.1 ng/ml (2-fold increase in RL) in the BC and from 38.3 +/- 17.7 (base line) to 294.4 +/- 38.1 ng/ml (50% increase in RL) in the PC (P less than 0.001 vs. baseline concentration) after a 0.1-mg/ml dose of 48/80.(ABSTRACT TRUNCATED AT 250 WORDS)
Oxygen delivery rate and sufficiency of oxygenation during ECMO in newborn baboons
Authors: Cornish J. D. , Gerstmann D. R. , Null D. M. , Smith M. D. , Kuehl T. J.
Published: December 2017

Minimum acceptable O2 delivery (DO2) during extracorporeal membrane oxygenation (ECMO) remains to be defined in a newborn primate model. The right atrium, carotid artery, and femoral artery were cannulated, and the ductus arteriosus, aorta, and pulmonary artery ligated in neonatal baboons (Papio cynocephalus) under a combination of ketamine, diazepam, and pancuronium. The internal jugular vein was also cannulated retrograde to the level of the occipital ridge. We measured hemoglobin, pH, arterial and venous PO2 (both from the pump circuit and from the cerebral venous site), serum lactate and bicarbonate concentrations, and pump flow, and we calculated hemoglobin saturations, (DO2), O2 consumption (VO2), systemic O2 extraction, and cerebral O2 extraction. Six baboons were studied during each of two phases of the experiment. In the first, flow rates were varied sequentially from 200 to 50 ml.kg-1.min-1 with saturation maximized. In the second, flow was maintained at 200 ml.kg-1.min-1 and saturation was reduced sequentially from 100 to 38%. VO2 fell significantly below baseline at a flow rate of 50 ml.kg-1.min-1 and a DO2 of 8 +/- 2 (SE) ml.kg-1.min-1 in phase 1 and at DO2 of 12 +/- 5 in phase 2. Both systemic and cerebral O2 extraction rose significantly at a flow of 100 ml.kg-1.min-1 and DO2 of 17 +/- 4 ml.kg-1.min-1 in phase 1, whereas neither rose with decreasing DO2 in phase 2. In fact, cerebral extraction fell significantly DO2 of 16 +/- 6 ml.kg-1.min-1.(ABSTRACT TRUNCATED AT 250 WORDS)
Neurogenic plasma extravasation: inhibition by morphine in guinea pig airways in vivo
Authors: Belvisi M. G. , Rogers D. F. , Barnes P. J.
Published: December 2017

Opioid drugs have been shown to inhibit neurogenic plasma exudation in skin by a presynaptic mechanism. We determined whether a similar inhibitory effect operates in the airways of anesthetized guinea pigs in vivo with the use of Evans blue dye as a marker of plasma leakage. Stimulation of the vagus nerve significantly increased leakage of dye in trachea and main bronchi (by approximately 300 and 600%, respectively). Similar increases in leakage were seen in the presence of atropine and propranolol. Morphine (1–30 mg/kg iv) inhibited leakage in a dose-related manner with complete inhibition in the trachea at a dose of 30 mg/kg. The inhibition was blocked by the opioid receptor-antagonist naloxone (1 mg/kg iv). Intravenous substance P significantly increased leakage but was not inhibited by morphine. We conclude that morphine inhibits neurogenic plasma leakage by presynaptic inhibition of release of neuropeptides from sensory nerve endings. If similar mechanisms are operative in human airways, inhibition of neurogenic plasma leakage by opioid drugs devoid of central effects may be of value in the therapy of asthma.
Whole-body protein metabolism in lactating and nonlactating women
Authors: Motil K. J. , Montandon C. M. , Hachey D. L. , Boutton T. W. , Klein P. D. , Garza C.
Published: December 2017

The adaptive responses of body protein metabolism to lactation were characterized in women at 1, 5, and 12 mo postpartum and in nulliparous controls during a controlled diet of measured protein and energy intakes by nitrogen balance, a constant infusion of [13C]bicarbonate, and a primed constant infusion of [1–13C]leucine and [alpha-15N]-lysine. Dietary energy intakes in the lactating women were 27% greater than those in the nulliparous controls. Despite these differences, lactating women had significantly lower nitrogen balances compared with the nonlactating women (-4.0 +/- 37.8 vs. +44.7 +/- 30.8 mg.kg-1.day-1). No significant differences in amino acid flux, oxidation, or incorporation into protein were detected during fasting conditions in the two groups of women. However, significantly positive associations were noted between dietary intakes and the variables of protein metabolism in the lactating women. A more complete understanding of the mechanisms that regulate the disposition of dietary nutrients into maternal body stores or milk production will enhance the determination of nutrient requirements in lactating women.
Distribution of pulmonary vascular pressure as a function of perinatal age in lambs
Authors: Tod M. L. , Sylvester J. T.
Published: December 2017

The distribution of pulmonary vascular resistance (PVR) with respect to compliance was determined using vascular occlusion in isolated lungs from lambs at five ages, from 2 wk before birth to 1 mo of age. The major change in PVR occurred in the pressure gradient across the middle compliant region (delta Pm), which dropped sharply at birth, remained low for 2 wk, and increased at 1 mo. Pulmonary vasoreactivity also varied with ages. Lungs at 0–4 days did not respond to hypoxia and responded poorly to prostaglandin F2 alpha (PGF2 alpha). In contrast, lungs at 13–33 days had significant increases in delta Pm and the gradient across relatively indistensible arterial vessels during hypoxia and increases in all gradients with PGF2 alpha. Ventilation of fetal lungs reduced PVR, mainly because of a 50% reduction in delta Pm. Our results demonstrate that the magnitude and distribution of PVR relative to compliance varied as a function of perinatal age and that pulmonary vasoreactivity depended on postnatal age. The major effect of ventilating fetal lungs was on the middle region.
Cytokines increase rat lung antioxidant enzymes during exposure to hyperoxia
Authors: White C. W. , Ghezzi P. , McMahon S. , Dinarello C. A. , Repine J. E.
Published: December 2017

Pretreatment with the combination of tumor necrosis factor/cachectin (TNF/C) and interleukin 1 (IL-1) increased glucose-6-phosphate dehydrogenase (G6PDH), glutathione reductase (GR), glutathione peroxidase (GPX), catalase (CAT), and superoxide dismutase (SOD) activities in lungs of rats continuously exposed to hyperoxia for 72 h, a time when all untreated rats had already died. Pretreatment with TNF/C and IL-1 also increased, albeit slightly, lung G6PDH and GR activities of rats exposed to hyperoxia for 4 or 16 h. By comparison, no differences occurred in lung antioxidant enzyme activities of TNF/C and IL-1- or saline-pretreated rats exposed to hyperoxia for 36 or 52 h; the latter is a time just before untreated rats began to succumb during exposure to hyperoxia. The results raise the possibility that TNF/C and IL-1 treatment can increase lung antioxidant enzyme activities and that increased lung antioxidant enzymes may contribute to the increased survival of TNF/C and IL-1-pretreated rats in hyperoxia for greater than 72 h.
Effects of beta 1- vs. beta 1 + beta 2-blockade on exercise endurance and muscle metabolism in humans
Authors: Cleroux J. , Van Nguyen P. , Taylor A. W. , Leenen F. H.
Published: December 2017

The effects of beta-blockade on muscle utilization of glycogen and triglycerides, as well as potassium metabolism, were studied in eight healthy male subjects performing long-duration exercise to exhaustion. Subjects were studied after treatment with either placebo (PLAC), beta 1-selective (atenolol, 100 mg/day, AT), or nonselective beta-blockade (nadolol, 80 mg/day, NAD) each for 1 wk according to a randomized, double-blind, cross-over design. NAD and AT caused identical decreases in exercise heart rates, but endurance (71 +/- 8 min with PLAC) decreased significantly more with NAD (-33 +/- 4%) than with AT (-14 +/- 6%). Muscle glycogen breakdown, taking exercise time into account, was unaffected by treatment. In contrast, muscle triglyceride utilization was completely blocked by NAD whereas it was unchanged with AT as compared to PLAC. Adipose tissue lipolysis was inhibited to a similar extent by the two beta-blockers. Serum potassium increased to higher levels at exhaustion and muscle potassium decreased to lower levels with NAD than with AT or PLAC. These results suggest that decreased utilization of muscle triglycerides combined with lack of an enhanced glycogenolysis to compensate as well as alterations in potassium metabolism contribute to the decreased exercise capacity with nonselective beta-blockade compared with beta 1-selective blockade.
Recovery of diaphragm function after laparotomy and chronic sonomicrometer implantation
Authors: Easton P. A. , Fitting J. W. , Arnoux R. , Guerraty A. , Grassino A. E.
Published: December 2017

If sonomicrometry transducers could be implanted permanently into the diaphragm, direct measurements of costal and crural length and shortening could be made during recovery from the laparotomy and then indefinitely in an awake, non-anesthetized mammal. We report results from six canines in which we successfully implanted transducers onto the left hemidiaphragm through a midline laparotomy and measured segmental shortening and ventilation at intervals through 22 days of postoperative recovery. After laparotomy, breathing pattern, including tidal volume, respiratory rate and mean inspiratory flow, stabilized by the 4th postoperative day (POD). Tidal shortening of costal and crural segments increased from 1.82 and 1.45% of end-expiratory length (%LFRC) on the 2nd POD to 5.32 and 8.56% LFRC, respectively, after a mean of 22 POD. Segmental shortening did not stabilize until 10 POD, and the recovery process displayed a sequence of segmental motions: lengthening, biphasic inspiratory lengthening-shortening, and increasing simple shortening. Three weeks after implantation, costal and crural segments were stable and shortening 5.32 and 8.56% LFRC, respectively, and capable of shortening 49% LFRC with maximal phrenic stimulation. In a pair of recovered animals, the initial postoperative dysfunction did not recur after a subsequent, simple laparotomy. At postmortem examination, the chronically implanted sonomicrometer transducers were found to have evoked only a thin fibrotic capsule within the diaphragm.
Cardiac adaptations to endurance training in rats with a chronic myocardial infarction
Authors: Musch T. I. , Moore R. L. , Smaldone P. G. , Riedy M. , Zelis R.
Published: December 2017

The hemodynamic response to maximal exercise was determined in sedentary and trained rats with a chronic myocardial infarction (MI) produced by coronary artery ligation and in rats that underwent sham operations (SHAM). Infarct size in the MI groups of rats comprised 28–29% of the total left ventricle and resulted in both metabolic and hemodynamic changes that suggested that these animals had moderate compensated heart failure. The training regimen used in the present study produced significant increases in maximal O2 uptake (VO2max) when expressed in absolute terms (ml/min) or when normalized for body weight (ml.min-1.kg-1) and consisted of treadmill running at work loads that were equivalent to 70–80% of the animal's VO2max for a period of 60 min/day, 5 days/wk over an 8- to 10-wk interval. This training paradigm produced two major cardiocirculatory adaptations in the MI rat that had not been elicited previously when using a training paradigm of a lower intensity. First, the decrement in the maximal heart rate response to exercise (known as “chronotropic incompetence”) found in the sedentary MI rat was completely reversed by endurance training. Second, the downregulation of cardiac myosin isozyme composition from the fast ATPase V1 isoform toward the slower ATPase (V2 and V3) isoforms in the MI rat was partially reversed by endurance training. These cardiac adaptations occurred without a significant increase in left ventricular pump function as an increase in maximal cardiac output (Qmax) and maximal stroke volume (SVmax) did not occur in the trained MI rat.(ABSTRACT TRUNCATED AT 250 WORDS)
Attenuation of hypoxic ventilation by hyperbaric O2: effects of pressure and exposure time
Authors: Liberzon I. , Arieli R. , Kerem D.
Published: December 2017

Hyperoxia affects O2 chemoreception in the highly perfused carotid bodies and causes a reduction of the ventilatory hypoxic drive (HD) as was shown for anesthetized cats and awake rats. We looked for a quantitative description of such an effect on HD as a function of both O2 pressure and exposure duration. Ventilation of rats was measured using the barometric method before and after hyperbaric O2 (HBO) exposure, at either air, 80% O2, or 4% O2. We used three exposure durations: 180, 550 and 900 min. The O2 pressure ranged between 1.2 and 3.0 ATA. At each time duration we used four to five groups of rats at a range of O2 pressures that yielded the full scale of effect on HD but avoided obvious lasting difficulties in breathing. HBO caused a reduction of breathing frequency and elevation of tidal volume in both air and 80% O2 but almost no change in minute ventilation. Hypoxic minute ventilation (4% O2) decreased after HBO, mainly through reduced frequency. HD was described by a power function of O2 pressure for each HBO duration. HD did not decline below 20% of the full control response. Ventilatory HD diminution is pictured as a function of both O2 pressure and HBO duration. The dependency of HD on exposure time and on pressure is similar to other known toxic effects of HBO.
High-frequency oscillations within early and late phases of the phrenic neurogram
Authors: Webber C. L.
Published: December 2017

Spectral analyses were performed on phrenic neurogram recordings from 18 cats to identify high-frequency oscillations (HFOs) inherent in the signals at different phases of inspiratory activity. Gating the analysis for the entire inspiratory phase resulted in dual spectral HFOs (27 and 83 Hz), both of which persisted when the analysis was repeated on the later phase of phrenic inspiratory activity alone (29 and 82 Hz). A third pass at the same data, gating for just the early phase of phrenic discharge, however, resulted in single spectral HFOs at the higher frequency only (86 Hz). Because both early and late recruited phrenic motoneurons carry both higher and lower spectral frequencies, these results demonstrate that the lower frequency HFO is distinctly delayed in onset compared with the higher frequency HFO, the latter of which is believed to have a brain stem origin. This delayed onset may be important in identifying the source of the lower frequency HFO, which appears to be specific to various respiratory efferent systems.
Tachykinins mediate bronchoconstriction elicited by isocapnic hyperpnea in guinea pigs
Authors: Ray D. W. , Hernandez C. , Leff A. R. , Drazen J. M. , Solway J.
Published: December 2017

We tested the hypothesis that tachykinins mediate hyperpnea-induced bronchoconstriction (HIB) in 28 guinea pigs. Stimulus-response curves to increasing minute ventilation with dry gas were generated in animals depleted of tachykinins by capsaicin pretreatment and in animals pretreated with phosphoramidon, a neutral metalloendopeptidase inhibitor. Sixteen anesthetized guinea pigs received capsaicin (50 mg/kg sc) after aminophylline (10 mg/kg ip) and terbutaline (0.1 mg/kg sc). An additional 12 animals received saline (1 ml sc) instead of capsaicin. One week later, all animals were anesthetized, given propranolol (1 mg/kg iv), and mechanically ventilated (6 ml/kg, 60 breaths/min, 50% O2 in air fully water saturated). Phosphoramidon (0.5 mg iv) was administered to five of the noncapsaicin-treated guinea pigs. Eucapnic dry gas (95% O2–5% CO2) hyperpnea “challenges” were performed by increasing the tidal volume (2–6 ml) and frequency (150 breaths/min) for 5 min. Capsaicin-pretreated animals showed marked attenuation in HIB, with a rightward shift of the stimulus-response curve compared with controls; the estimated tidal volume required to elicit a twofold increase in respiratory system resistance (ES200) was 5.0 ml for capsaicin-pretreated animals vs. 3.7 ml for controls (P less than 0.03). Phosphoramidon-treated animals were more reactive to dry gas hyperpnea compared with control (ES200 = 2.6 ml; P less than 0.0001). Methacholine dose-response curves (10(-11) to 10(-7) mol iv) obtained at the conclusion of the experiments were similar among capsaicin, phosphoramidon, and control groups. These findings implicate tachykinin release as an important mechanism of HIB in guinea pigs.
Effects of sleep deprivation on respiratory events during sleep in healthy infants
Authors: Canet E. , Gaultier C. , D'Allest A. M. , Dehan M.
Published: December 2017

This study was designed to determine the effects of sleep deprivation on respiratory events during sleep in healthy infants. Ten unsedated full-term infants (1–6 mo) were monitored polygraphically during “afternoon naps” on a control day and on the day after sleep deprivation. Respiratory events, i.e., central apnea, obstructive apnea and hypopnea, and periodic breathing were tabulated. Results for respiratory events were expressed as 1) indexes of the total number of respiratory events and of specific respiratory events per hour of total sleep (TST), “quiet” sleep (QS) and “active” sleep (AS) times; 2) total duration of total and specific respiratory events, expressed as a percentage of TST, QS, and AS times. After sleep deprivation, significant increases were observed for 1) respiratory event (P less than 0.001), central apnea (P less than 0.05), and obstructive respiratory event (P less than 0.01) indexes; 2) respiratory event time as a percentage of TST (P less than 0.002) and as a percentage of AS time (P less than 0.001); 3) obstructive respiratory event time as a percentage of TST (P less than 0.01), QS (P less than 0.05), and AS times (P less than 0.002). The present study shows that short-term sleep deprivation in healthy infants increases the number and timing of respiratory events, especially obstructive events in AS.
Assessment of temporal changes in pulmonary edema with NMR imaging
Authors: Phillips D. M. , Allen P. S. , Man S. F.
Published: December 2017

Nuclear magnetic resonance imaging (NMRI) parameters [longitudinal relaxation time (T1), transverse relaxation time (T2), and signal intensity] acquired at a magnetic field of 2.35 T were validated with a study of nine different phantom gel solutions. This technique was then applied to study 13 anesthetized supine cats, among which 10 had lung edema induced by oleic acid (0.075 ml/kg); the result was compared with postmortem analyses of lung water. Three animals (series A) were imaged until the edema was first visualized in NMRI, usually 15–20 min after oleic acid infusion. Another seven animals (series B) were imaged over 4–5 h. As lung water increased, so did the signal intensity. When edema first appeared, T1, T2, and the volume of the edematous region within the slice in the upper lobes showed no gravity-dependent differences; this was confirmed by postmortem measurements (series A) of lung water. With time, gravity-dependent regions displayed greater volumes of edematous regions and greater T1 values (P less than 0.01), suggesting a continued accumulation of lung water. In comparison, nondependent regions displayed constant volumes of edematous region and lesser T1 values (P less than 0.01), suggesting an increased protein concentration but no change in lung water. This study suggests the potential applicability of NMRI parameters in the assessment of pulmonary edema.
Measurement of O2 consumption in isolated organs without venous cannulation
Authors: DeGrado T. R. , Holden J. E. , Ng C. K. , Raffel D. M. , Gatley S. J.
Published: December 2017

A new two-sensor technique for measurement of O2 consumption in isolated organs without venous cannulation was successfully applied to the isolated rat heart. Because this technique eliminates the net exchange of O2 between venous effluent and the environment, measurement of the O2 concentration is conveniently made by use of a polarographic sensor in a collected pool of effluent at the bottom of a closed organ chamber. The method was validated against conventional techniques using cannulation of the pulmonary artery. The two-sensor technique allows O2 consumption measurements to be made in isolated organ preparations in which representative venous cannulation is prohibitively difficult, for example in organs with multiple venous drains, or those in which cannulation would be expected to cause excessive perturbation of physiological status.
Gas exchange in healthy rabbits during high-frequency oscillatory ventilation
Authors: Boynton B. R. , Hammond M. D. , Fredberg J. J. , Buckley B. G. , Villanueva D. , Frantz I. D.
Published: December 2017

We examined the effects of oscillatory frequency (f), tidal volume (VT), and mean airway pressure (Paw) on respiratory gas exchange during high-frequency oscillatory ventilation of healthy anesthetized rabbits. Frequencies from 3 to 30 Hz, VT from 0.4 to 2.0 ml/kg body wt (approximately 20–100% of dead space volume), and Paw from 5 to 20 cmH2O were studied. As expected, both arterial partial pressure of O2 and CO2 (PaO2 and PaCO2, respectively) were found to be related to f and VT. Changing Paw had little effect on blood gas tensions. Similar values of PaO2 and PaCO2 were obtained at many different combinations of f and VT. These relationships collapsed onto a single curve when blood gas tensions were plotted as functions of f multiplied by the square of VT (f. VT2). Simultaneous tracheal and alveolar gas samples showed that the gradient for PO2 and PCO2 increased as f. VT2 decreased, indicating alveolar hypoventilation. However, venous admixture also increased as f. VT2 decreased, suggesting that ventilation-perfusion inequality must also have increased.
Effect of hypercapnia and PEEP on expiratory muscle EMG and shortening
Authors: Oliven A. , Kelsen S. G.
Published: December 2017

The present study examined the effects of hypercapnia and positive end-expiratory pressure (PEEP) on the electromyographic (EMG) activity and tidal length changes of the expiratory muscles in 12 anesthetized, spontaneously breathing dogs. The integrated EMG activity of both abdominal (external oblique, internal oblique, rectus abdominis, and transverse abdominis) and thoracic (triangularis sterni, internal intercostal) expiratory muscles increased linearly with increasing PCO2 and PEEP. However, with both hypercapnia and PEEP, the percent increase in abdominal muscle electrical activity exceeded that of thoracic expiratory muscle activity. Both hypercapnia and PEEP increased the tidal shortening of the external oblique and rectus abdominis muscles. Changes in tidal length correlated closely with simultaneous increases in muscle electrical activity. However, during both hypercapnia and PEEP, length changes of the external oblique were significantly greater than those of the rectus abdominis. We conclude that both progressive hypercapnia and PEEP increase the electrical activity of all expiratory muscles and augment their tidal shortening but produce quantitatively different responses in the several expiratory muscles.
Methylene blue selectively inhibits pulmonary vasodilator responses in cats
Authors: Hyman A. L. , Kadowitz P. J. , Lippton H. L.
Published: December 2017

The effects of methylene blue on vascular tone and the responses to pressor and depressor substances were investigated in the constricted feline pulmonary vascular bed under conditions of controlled blood flow and constant left atrial pressure. When tone was elevated with U46619, intralobar injections of acetylcholine, bradykinin, nitroglycerin, isoproterenol, epinephrine, and 8-bromoguanosine-3′,5′-cyclic monophosphate (8-bromo-cGMP) dilated the pulmonary vascular bed. Intralobar infusions of methylene blue elevated lobar arterial pressure without altering base-line left atrial or aortic pressure, heart rate, or cardiac output. When methylene blue was infused in concentrations that raised lobar arterial pressure to values similar to those attained during U46619 infusion, the pulmonary vasodilator responses to acetylcholine, bradykinin, and nitroglycerin were reduced significantly, whereas vasodilator responses to isoproterenol, epinephrine, and 8-bromo-cGMP were not altered. Moreover, the pressor responses to angiotensin II and BAY K 8644 during U46619 infusion and during methylene blue infusion were similar. The enhancing effects of methylene blue on vascular tone and inhibiting effects of this agent on responses to acetylcholine, bradykinin, and nitroglycerin were reversible. These responses returned to control value when tone was again increased with U46619, 30–45 min after the methylene blue infusion was terminated. The present data are consistent with the hypothesis that cGMP may play a role in the regulation of tone in the feline pulmonary vascular bed and in the mediation of vasodilator responses to the endothelium-dependent vasodilators, acetylcholine and bradykinin, and to nitrogen oxide-containing vasodilators such as nitroglycerin.
Lung edema increases transvascular filtration rate but not filtration coefficient
Authors: Parker J. C. , Townsley M. I. , Cartledge J. T.
Published: December 2017

To determine whether the accelerated rate of lobe weight gain during severe pulmonary edema is attributed to increased permeability of the microvascular barrier or a loss of tissue forces opposing filtration, the effect of edema on capillary filtration coefficient (Kf,C), interstitial compliance (Ci), and the volume of fluid filtered after a step increase in microvascular pressure (delta Vi) were determined in eight isolated left lower lobes of dog lungs perfused at 37 degrees C with autologous blood. After attaining a base-line isogravimetric state, the capillary pressure (Pc) was increased in successive steps of 2, 5, and 10 cmH2O. This sequence of vascular pressure increases was repeated three times. Edema accumulation was expressed as weight gained as a percent of initial lobe weight (% delta Wt), and Kf,C was measured by time 0 extrapolation of the weight gain curve. An exponential rate constant for the decrease in the rate of weight gain with time (K) was calculated for each curve. Ci was then calculated by assuming that the capillary wall and interstitium constitute a resistance-capacitance network. Kf,C was not increased by edema formation in any group. Between mild (% delta Wt less than 30%) and severe edema states (% delta Wt greater than 50%) respective mean Ci increased significantly from 3.54 to 9.12 ml.cmH2O-1.100 g-1, K decreased from 0.089 to 0.036 min-1, and delta Vi increased from 1.28 to 2.4 ml.cmH2O-1.100 g-1. The delta Vi during each Pc increase was highly correlated with Kf,C and Ci when used together as independent variables (r = 0.99) but less well correlated when used separately.(ABSTRACT TRUNCATED AT 250 WORDS)
A vagally mediated response to metabolic acidosis in anesthetized rabbits
Authors: Maskrey M. , Trenchard D.
Published: December 2017

Pentobarbital sodium-anesthetized rabbits received 10-min infusions of acetic, lactic, or propionic acid delivered via a catheter to the right atrium at a rate of 1 mmol/min (n = 14). Arterial [H+] increased by 35.8 +/- 7.6 (SD) nmol/l, a decrease in pH of 0.27 +/- 0.04. By the end of the infusion period respiratory frequency (f), tidal volume (VT), and minute ventilation (V) had increased by 15.5 +/- 6.2 breaths/min, 7.3 +/- 2.7 ml, and 0.86 +/- 0.34 l/min, respectively. Arterial PCO2 (PaCO2) increased initially, but isocapnia was established during the latter half of the infusion (delta PaCO2 = 0.4 +/- 2.0 Torr). Bilateral cervical vagotomy eliminated the f response to acid infusions (n = 9, delta f = 0.6 +/- 2.4 breaths/min). The increase in VT (12.6 +/- 3.1 ml) was greater, but that in V (0.39 +/- 0.11 l/min) was less than in intact animals (P less than 0.05). PaCO2 remained elevated throughout the infusion (delta PaCO2 = 5.5 +/- 2.6 Torr), resulting in a greater rise in arterial [H+] (delta[H+]a = 53.6 +/- 6.6 nmol/l, delta pHa = -0.37 +/- 0.04). It is concluded that vagal afferents play a role in the f response to acute metabolic acidosis in rabbits.
Prevention of myocardial disease in JCR:LA-corpulent rats by running
Authors: Russell J. C. , Amy R. M. , Manickavel V. , Dolphin P. J. , Epling W. F. , Pierce D. , Boer D. P.
Published: December 2017

The JCR:LA-corpulent rat is a congenic strain that, if homozygous for the cp gene, is obese with a very low-density lipoprotein hyperlipidemia and is insulin resistant. The male corpulent rats develop atherosclerotic lesions of the major arteries and myocardial lesions. Corpulent and lean male rats were induced through mild food restriction to run intensively (approximately 6,000 m/day) from 6 wk to 6 mo of age. Food restriction, especially when coupled with running, lowered all classes of lipids in the whole serum of corpulent rats. The principal changes in lipid concentrations were in the very low-density lipoprotein fraction. Food restriction caused a significant drop in fasting insulin levels of corpulent rats and decreased beta-cell hyperplasia. Both effects were more marked in the running animals. There was a significant decrease in myocardial lesion frequency in the food-restricted corpulent rats and an absence of lesions in the running rats. The results indicate that intensive physical activity can largely correct the lipid abnormalities and insulin resistance of this atherosclerosis-prone strain, and these changes are associated with inhibition of the disease process. However, moderate food restriction has similar effects, and the greater effects seen with intensive running may simply reflect an effectively more severe metabolic restriction in the presence of the exercise.
Lithium clearance in water immersion-induced natriuresis in humans
Authors: Rabelink T. J. , Koomans H. A. , Boer W. H. , van Rijn J. , Dorhout Mees E. J.
Published: December 2017

Lithium clearance (CLi) has been advanced as a measure of sodium delivery from the proximal tubules. Because information on the intrarenal effects of water immersion is only limited, and available data are conflicting with respect to the effects on the proximal tubule, we examined the effects of 3 h of water immersion on renal functional parameters, including CLi, in eight healthy subjects. Studies were carried out during maximal water diuresis. Water immersion resulted in a significant increase in sodium excretion, from preimmersion values of 74.0 +/- 9.6 to 155.4 +/- 12.0 mumol/min at the third immersion hour (P less than 0.01). This natriuresis was accompanied by an increase in CLi from 26.3 +/- 1.9 (preimmersion) to 37.0 +/- 3.1 ml/min (P less than 0.01). Fractional lithium reabsorption (FRLi) decreased from 76.4 +/- 1.0 to 69.6 +/- 1.3% (P less than 0.01). None of these changes was found in eight healthy subjects undergoing a time-control study without water immersion. The large fall in FRLi found during immersion is compatible with a major resetting of the proximal glomerulotubular balance. In this regard the renal response to water immersion resembles saline expansion rather than mere intravascular expansion. The lithium data suggested a large rise in distal delivery accompanied by an almost as large rise in distal reabsorption. The free water clearance data were in agreement with this interpretation. However, no changes were found in fractional excretion of phosphate and uric acid. Therefore such a major resetting of proximal glomerulotubular balance can be doubted.(ABSTRACT TRUNCATED AT 250 WORDS)
A comparison of preterm and adult airway smooth muscle mechanics
Authors: Panitch H. B. , Allen J. L. , Ryan J. P. , Wolfson M. R. , Shaffer T. H.
Published: December 2017

To determine whether airway smooth muscle undergoes a maturational change regarding force generation, length-tension relationships were determined in isolated trachealis strips from adult and preterm sheep. At the length of maximum force generation, passive active and total tensions of the adult muscle were 2.5 times greater than preterm values (P less than 0.001). KCl stimulation yielded a greater peak tension in the adult strips than in the preterm strips (P less than 0.01). Preterm strips required higher concentrations of KCl to initiate contractions and higher concentrations to reach peak tension. Acetylcholine- (ACh) induced contraction resulted in greater force development at each dose in the adult strips compared with preterm strips (P less than 0.001). The dose of ACh required to reach a half-maximal response was significantly less for the adult strips than for the preterm strips (P less than 0.005). These data demonstrate that both force generation and receptor sensitivity increase with age. This inability of immature smooth muscle to generate as much force as adult smooth muscle may help explain why very preterm neonates requiring intermittent positive-pressure ventilation are at risk for developing structural airway problems.
Thermoregulation during cold water immersion is unimpaired by low muscle glycogen levels
Authors: Young A. J. , Sawka M. N. , Neufer P. D. , Muza S. R. , Askew E. W. , Pandolf K. B.
Published: December 2017

This investigation studied the importance of muscle glycogen levels for body temperature regulation during cold stress. Physiological responses of eight euglycemic males were measured while they rested in cold (18 degrees C, stirred) water on two separate occasions. The trials followed a 3-day program of diet and exercise manipulation designed to produce either high (HMG) or low (LMG) preimmersion glycogen levels in the muscles of the legs, arms, and upper torso. Preimmersion vastus lateralis muscle glycogen concentrations were lower during the LMG trial (144 +/- 14 mmol glucose/kg dry tissue) than the HMG trial (543 +/- 53 mmol glucose/kg dry tissue). There were no significant differences between the two trials in shivering as reflected by aerobic metabolic rate or in the amount of body cooling as reflected by changes in rectal temperature during the immersions. Postimmersion muscle glycogen levels remained unchanged from preimmersion levels in both trials. Small but significant increases in plasma glucose and lactate concentration occurred during both immersions. Plasma glycerol increased during immersion in the LMG trial but not in the HMG trial. Plasma free fatty acid concentration increased during both immersion trials, but the change was apparent sooner in the LMG immersion. It was concluded that thermoregulatory responses of moderately lean and fatter individuals exposed to cold stress were not impaired by a substantial reduction in the muscle glycogen levels of several major skeletal muscle groups. Furthermore, the data suggest that, depending on the intensity of shivering, other metabolic substrates are available to enable muscle glycogen to be spared.
Effect of exogenous surfactant instillation on experimental acute lung injury
Authors: Harris J. D. , Jackson F. , Moxley M. A. , Longmore W. J.
Published: December 2017

Pulmonary surfactant replacement has previously been shown to be effective in the human neonatal respiratory distress syndrome. The value of surfactant replacement in models of acute lung injury other than quantitative surfactant deficiency states is, however, uncertain. In this study an acute lung injury model using rats with chronic indwelling arterial catheters, injured with N-nitroso-N-methylurethane (NNNMU), has been developed. The NNNMU injury was found to produce hypoxia, increased mortality, an alveolitis, and alterations in the pulmonary surfactant system. Alterations of surfactant obtained by bronchoalveolar lavage included a reduction in the phospholipid-to-protein ratio, reduced surface activity, and alterations in the relative percentages of the individual phospholipids compared with controls. Treatment of the NNNMU-injured rats with instilled exogenous surfactant (Survanta) improved oxygenation; reduced mortality to control values; and returned the surfactant phospholipid-to-protein ratio, surface activity, and, with the exception of phosphatidylglycerol, the relative percentages of individual surfactant phospholipids to control values.