bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of altitude acclimatization on fluid regulatory hormone response to submaximal exercise
Authors: Rock P. B. , Kraemer W. J. , Fulco C. S. , Trad L. A. , Malconian M. K. , Rose M. S. , Young P. M. , Cymerman A.
Published: December 2017

To determine the effect of altitude acclimatization on plasma levels of atrial natriuretic peptide (ANP) during submaximal exercise and its relationship with renin and aldosterone, seven male volunteers aged 17–23 yr exercised to exhaustion on a cycle ergometer at 80–85% of their maximum O2 uptake at sea level (SL; 50 m), during 1 h in a hypobaric chamber [acute altitude (AA); 4,300 m], and after 14 or 16 days of residence on the summit of Pikes Peak, CO [chronic altitude (CA); 4,300 m]. Plasma samples taken before exercise, 10 min after the start of exercise, and 5 min postexercise were analyzed for ANP, plasma renin activity (PRA), and aldosterone (ALDO). ANP showed a progressive increase from rest to postexercise [7.49 +/- 1.63 to 11.32 +/- 1.80 (SE) pmol/ml and 6.05 +/- 2.55 to 10.38 +/- 7.20 pmol/ml; P = 0.049, exercise] at SL and AA, respectively, but not at CA (P = 0.039, altitude). Similarly, PRA and ALDO rose from rest to postexercise (P < 0.001, exercise), but the rise in ALDO with exercise was less during AA than during SL and CA (P = 0.002, phase). The decreased ANP levels during exercise after altitude acclimatization, with no change in PRA and ALDO, suggest that ANP has little effect on PRA and ALDO under these conditions.
Effect of concentric exercise on serum muscle and collagen markers
Authors: Virtanen P. , Viitasalo J. T. , Vuori J. , Vaananen K. , Takala T. E.
Published: December 2017

The effect of an acute bout of high-intensity concentric exercise on serum muscle and collagen marker proteins was studied in nine male students. The muscle-derived serum carbonic anhydrase III, myoglobin, and creatine kinase all increased as a result of the exercise. Serum type I procollagen carboxyterminal propeptide decreased at first but started to increase 2 days after the exercise. Serum galactosylhydroxylysyl glucosyltransferase was elevated immediately after the exercise. No significant changes were seen in the concentrations of serum amino-terminal propeptide of type III procollagen or 4-hydroxyproline. It seems that a single bout of heavy concentric exercise causes protein leakage from muscles and probably from the collagen-synthesizing cells of the connective tissue, which may be accompanied by an initial decrease and a subsequent increase in type I collagen production. The activation of type I collagen production seems to depend on the strain and damage of the musculoskeletal system.
Exercise training alters endothelium-dependent vasoreactivity of rat abdominal aorta
Authors: Delp M. D. , McAllister R. M. , Laughlin M. H.
Published: December 2017

We tested the hypothesis that adaptations in peripheral arterial vasoreactivity are induced by exercise training. Male rats were trained to run on a treadmill at 30 m/min (15 degrees incline) for 1 h/day 5 days/wk for 10–12 wk. Efficacy was indicated by a 51% increase (P < 0.05) in citrate synthase activity in soleus muscle of exercise-trained (ET) rats compared with that of sedentary (SED) control rats. Responses to vasoactive compounds were examined in vitro using rings of abdominal aorta. Maximal isometric contractile tension evoked by KCl, norepinephrine (NE), and phenylephrine were not different between groups; sensitivity to phenylephrine was also not different between groups. However, sensitivity was lower for both KCl and NE in vessels from ET animals. Endothelium removal did not influence KCl sensitivity but did abolish the difference in NE sensitivity of vessel segments between ET and SED animals. Maximal vasodilator responses induced by acetylcholine (ACh; NE or prostaglandin F2 alpha preconstriction) were greater in vessel rings from ET rats. However, dilatory responses by sodium nitroprusside (NE or prostaglandin F2 alpha preconstriction) and forskolin (NE preconstriction) were not different between groups, indicating that the augmented ACh-induced dilatory response resulted from an adaptation of the endothelium. Blockade of nitric oxide synthase activity diminished ACh-induced vasodilation by 79 and 100% in SED and ET rats, respectively. These results indicate that training alters vasomotor function in rat abdominal aortas through adaptations of both endothelium and smooth muscle.
Effect of diaphragmatic fatigue on control of respiratory muscles and ventilation during CO2 rebreathing
Authors: Yan S. , Lichros I. , Zakynthinos S. , Macklem P. T.
Published: December 2017

We studied the influence of diaphragmatic fatigue on the control of ventilation and respiratory muscle contribution to pressure swings in six normal seated subjects. CO2 was rebreathed before and after diaphragmatic fatigue induced by breathing against an inspiratory resistance requiring 60% maximal transdiaphragmatic pressure with each breath until exhaustion. After diaphragmatic fatigue for a given level of end-tidal PCO2, we found that tidal volume, breathing frequency, minute ventilation, duty cycle, and mean inspiratory flow did not change; esophageal pressure swings were the same, but gastric and transdiaphragmatic pressure swings were decreased; and the slope of the transpulmonary pressure-gastric pressure relationship determined at zero flow points at end expiration and end inspiration was increased. End-expiratory transpulmonary pressure progressively decreased and end-expiratory gastric pressure progressively increased with increasing end-tidal PCO2 by the same magnitude before and after diaphragmatic fatigue. We conclude that diaphragmatic fatigue induces proportionately greater contributions of inspiratory rib cage muscles than of the diaphragm, which results in the preservation of ventilatory response to CO2 despite impaired diaphragmatic contractility.
Effect of global inspiratory muscle fatigue on ventilatory and respiratory muscle responses to CO2
Authors: Yan S. , Sliwinski P. , Gauthier A. P. , Lichros I. , Zakynthinos S. , Macklem P. T.
Published: December 2017

We evaluated the effect of global inspiratory muscle fatigue on ventilation and respiratory muscle control during CO2 rebreathing in normal subjects. Fatigue was induced by breathing against a high inspiratory resistance until exhaustion. CO2 response curves were measured before and after fatigue. During CO2 rebreathing, global fatigue caused a decreased tidal volume (VT) and an increased breathing frequency but did not change minute ventilation, duty cycle, or mean inspiratory flow. Both esophageal and transdiaphragmatic pressure swings were significantly reduced after global fatigue, suggesting decreased contribution of both rib cage muscles and diaphragm to breathing. End-expiratory transpulmonary pressure for a given CO2 was lower after fatigue, indicating an additional decrease in end-expiratory lung volume due to expiratory muscle recruitment, which leads to a greater initial portion of inspiration being passive. This, combined with the reduction in VT, decreased the fraction of VT attributable to inspiratory muscle contribution; therefore the inspiratory muscle elastic work and power per breath were significantly reduced. We conclude that respiratory control mechanisms are plastic and that the respiratory centers alter their output in a manner appropriate to the contractile state of the respiratory muscles to conserve the ventilatory response to CO2.
HEPES buffer perfusate alters rabbit lung endothelial permeability
Authors: Douglas G. C. , Swanson J. A. , Kern D. F.
Published: December 2017

N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) has been shown to cause changes in cultured endothelial cells and smooth muscle function at concentrations from 5 to 25 mM. To determine whether HEPES also affects vascular permeability, the effects of two buffers, HEPES and phosphate, were compared in isolated perfused rabbit lungs. Hemodynamic parameters and vascular protein permeability-surface area products (PS) were measured after perfusion with the buffers. Endothelial permeability was measured for an anionic and a cationic albumin to assess the charge effects of the zwitterion buffer. With HEPES, there were no changes in vascular pressure or resistance but permeability was affected. Cationic albumin permeability increased with 12 mM HEPES (8.7phosphate-->30(12) mM HEPES x ml.min-1.g dry lung-1 x 10(-2)) as did the anionic albumin PS (2.7phosphate-->3.52(12) mM HEPES). The cationic PS returned to baseline (8.1(60) mM HEPES) at 60 mM HEPES, but the anionic PS did not change from the 12 mM HEPES (4.01(60) mM HEPES). In summary, we find that HEPES is not innocuous. Although hemodynamic parameters did not change, endothelial permeability was increased when HEPES was used at normal concentrations. Therefore, HEPES should be used with caution as a physiological buffer in perfused organ systems.
Effect of training on eccentric exercise-induced muscle damage
Authors: Balnave C. D. , Thompson M. W.
Published: December 2017

Eccentric muscle contractions generate delayed onset muscle soreness (DOMS), possibly as a result of the high tensions involved causing muscle damage. Muscle function, serum indicators of muscle damage, and DOMS were investigated throughout a training regimen that involved a 40-min eccentric walk down a 25% gradient on a treadmill at 6.4 km/h once a week for 8 wk. Serum creatine kinase and myoglobin concentrations were used as indicators of muscle damage, and both demonstrated a delayed increase after the exercise protocol. The muscles that contracted eccentrically exhibited low-frequency fatigue, as well as decreases in muscle fatigability and maximal voluntary contraction force, which were greatest immediately postexercise. Although the results show that training reduces DOMS, the serum muscle protein response, and muscle function impairment, the time courses of these adaptations are different. It is suggested that the function of the muscle can be impaired without apparent muscle damage.
Blood volume expansion, preeclampsia, and infant birth weight at high altitude
Authors: Zamudio S. , Palmer S. K. , Dahms T. E. , Berman J. C. , McCullough R. G. , McCullough R. E. , Moore L. G.
Published: December 2017

Low blood volume (BV) during pregnancy is associated with intrauterine growth retardation and preeclampsia, which are more common at high altitude (HA) than at low altitude. We hypothesized that reduced BV expansion during pregnancy predisposed some women to develop preeclampsia and/or have lower-birth-weight infants at HA. BV was lower in 34 HA residents (3,100 m) than in 22 moderate-altitude residents (1,600 m) while nonpregnant (58.3 +/- 1.2 vs. 72.3 +/- 1.3 ml/kg; P < 0.001) and 36 wk pregnant (69.9 +/- 1.9 vs. 83.3 +/- 3.6 ml/kg; P < 0.01). BV fell between weeks 24 and 36 of pregnancy, and total BV increment with pregnancy was less in women who developed preeclampsia or transient hypertension at HA (n = 12). At HA, total blood and plasma volume expansion and arterial O2 saturation correlated negatively with the highest mean arterial pressure recorded during pregnancy (r = -0.73, P < 0.01 and r = -0.58, P < 0.01, respectively). Total BV and late pregnancy change in BV correlated positively with infant birth weight. We concluded that BV expansion in normotensive pregnancy at HA vs. moderate altitude was similar but that nonpregnant BV was less among HA women, accounting for the low BV in pregnancy. HA women who developed preeclampsia or transient hypertension had less BV expansion, particularly during the third trimester, which was associated with smaller infants.
Dynamics of carotid body responses in vitro in the presence of CO2-HCO3-: role of carbonic anhydrase
Authors: Iturriaga R. , Mokashi A. , Lahiri S.
Published: December 2017

The role of carbonic anhydrase (CNA) in the dynamics of carotid body (CB) function was tested by studying the effects of the membrane-permeable CNA inhibitor methazolamide on the chemosensory responses of the cat CB, perfused and superfused in vitro with cell-free and modified Tyrode solution at 36.5 +/- 0.5 degrees C in the presence of CO2-HCO3- (PO2 = 120 Torr, PCO2 = 32 Torr, pH = 7.40). The bulk of CO2 flow to the CB from the external milieu was overwhelmingly large relative to the metabolic production of CO2 in the CB. Accordingly, the relative contribution of the endogenous CO2 to the CB responses was small. The chemosensory nerve discharges were recorded from the whole desheathed carotid sinus nerve. The responses to acidic hypercapnia (PCO2 = 50–60 Torr, pH = 7.20–7.10), hypoxia (PO2 = 25 and 50 Torr), perfusate flow interruption, and bolus injections of sodium cyanide (20–40 nmol) were tested. To contrast, we also measured the effects of nicotine (2–4 nmol), which may act at sites other than those for O2 and CO2. Methazolamide (30 mg/l) in the perfusate at constant PCO2 and pH reduced the baseline activity and delayed the responses to step changes in PCO2 (and concomitantly pH) and PO2 and to cyanide but not to nicotine. The steady-state responses to these stimuli, measured as differences from control, were reduced, but not significantly. The initial overshoots seen with step changes in both high PCO2 and low PO2 were eliminated.(ABSTRACT TRUNCATED AT 250 WORDS)
Human red blood cell aging at 5,050-m altitude: a role during adaptation to hypoxia
Authors: Samaja M. , Brenna L. , Allibardi S. , Cerretelli P.
Published: December 2017

O2 uptake (VO2) kinetics at the onset of a constant work rate exercise are difficult to describe for work rates above the lactic acidosis threshold (LAT), because the steady-state level of VO2 response can usually not be identified. To describe the ability of the O2 transport system to deliver and the cells to utilize O2 above the LAT relative to that below the LAT, we applied a fluctuating (sinusoidal) variation of work rate. After 4 min of constant work at the midpoint of the sinusoidal work rate, a fluctuating work rate, at a period of 4 min, was applied below the LAT for the next 16 min. This was repeated in a range of work rates above the LAT with the same sine-wave amplitude. VO2 response appeared to follow a sinusoidal pattern similar to that of work rate for below- and above-LAT exercise. However, the amplitude of the VO2 response was significantly reduced (5.4 +/- 2.6 vs. 7.6 +/- 1.9 ml.min-1 x W-1, P < 0.01), and the phase lag increased above- compared with below-LAT work rate. VO2/heart rate fluctuations were dramatically reduced, whereas heart rate amplitude decreased and phase lag increased, for above-LAT sinusoidal work rate changes. These results suggest that VO2 kinetics are slowed in the work rate domain above the LAT relative to that below the LAT and that VO2 kinetics could be limited by the O2 transport mechanisms to the exercising muscle.
Gas exchange in a three-compartment lung model analyzed by forcing sinusoids of N2O
Authors: Hahn C. E. , Black A. M. , Barton S. A. , Scott I.
Published: December 2017

A mathematical gas exchange model, using sinusoidal forcing functions of inert inspired gas (A. Zwart, R. C. Seagrave, and A. Van Dieren. J. Appl. Physiol. 41: 419#x2013;424, 1976), has been extended by us to include dead space (VD), a single alveolar compartment (VA) perfused with blood flow (Qp), and a shunt (Qs). In this new work we use N2O as the indicator gas in the mathematical model and in the experimental studies, in low enough concentrations [<6% (vol/vol)] to avoid anesthetic effects. Mathematical relationships between the inspired and expired N2O gas partial pressures, the blood gas N2O partial pressures, and their variation with forcing frequency are derived for a continuous ventilation uptake and a conventional anesthetic gas distribution model. We show that these gas and blood gas N2O relationships give direct derivation of cardiorespiratory parameters such as VA, Qp, the dead space-to-total ventilation ratio (VD/VT), and the shunt-to-total blood flow ratio (Qs/QT) without altering the subject's oxygenation and that they are essentially free from recirculation effects at high forcing frequencies > or = 2 min-1. Theoretical results from the model are presented for a wide range of forcing frequencies between 2 x 10(-2) and 10 min-1 (sinusoid periods 30#x2013;0.1 min), and these show that VA, Qp, and VD/VT can all be measured by N2O forcing frequencies > or = 1 min-1. We also present results from five animal studies, with an experimental inspired gas forcing frequency range of 0.125 to 2 min-1, which show qualitative agreement with the predictions of the continuous ventilation model. During these animal studies both mass spectrometric N2O respiratory gas measurements and intravascular polarographic arterial and mixed venous blood N2O partial pressure measurements were made, and examples of these in vivo measurements are presented, together with examples of the calculations derived from them.
Thromboxane receptor stimulation/inhibition and perfusion redistribution after acute lung injury
Authors: Schuster D. P. , Sandiford P. , Stephenson A. H.
Published: December 2017

Perfusion redistribution (PR) after acute oleic acid (OA) lung injury may be the result of changes in the tissue concentration ratio of thromboxane (Tx) and prostacyclin (A. H. Stephenson et al. J. Appl. Physiol. 73: 2126–2134, 1992). We tested this hypothesis by determining whether the Tx mimetic U-46619 would mimic PR caused by cyclooxygenase inhibition with meclofenamate and whether the Tx receptor antagonist ONO-3708 would inhibit PR even in the presence of meclofenamate. Measurements of regional pulmonary blood flow (PBF) and lung water concentration were made with the nuclear medicine imaging technique of positron emission tomography. Measurements were made at baseline and 2 h after OA. At baseline, the spatial distribution of PBF was similar in all experimental groups. Two hours after OA, fractional PBF was reduced to the edematous lung in all groups given OA, but the magnitude of change was greater in those groups receiving meclofenamate or U-46619 compared with the change in the group given OA only. Thus, although the Tx mimetic produced the same amount of PR as meclofenamate, Tx inhibition did not prevent PR after meclofenamate. Therefore, the ratio of Tx to prostacyclin per se is not the critical determinant of PR.
Diethylmaleate produces diaphragmatic impairment after resistive breathing
Authors: Morales C. F. , Anzueto A. , Andrade F. , Levine S. M. , Maxwell L. C. , Lawrence R. A. , Jenkinson S. G.
Published: December 2017

Formation of oxygen-derived free radicals and activation of the glutathione (GSH) redox cycle has been associated with impaired rat diaphragm performance. Diethylmaleate (DEM) given intraperitoneally irreversibly conjugates with GSH, resulting in marked decreases in tissue concentrations of GSH. We have investigated the effects of acute GSH depletion by DEM on diaphragmatic function during resistive breathing (RB) in the rat. The experimental groups were 1) control, 2) DEM alone, 3) RB, and 4) DEM with RB (DEM + RB). RB was obtained by inspiratory RB until the rats were unable to sustain 70% of maximum airway opening pressure. A portion of the diaphragm was frozen for biochemical assays, and the rest of the diaphragm was prepared for measurement of in vitro contractile properties, including maximum tetanic tension, twitch tension, force-frequency curves, and contraction times. DEM treatment produced a profound depletion of GSH in the DEM and DEM + RB groups. Neither DEM nor RB alone significantly altered diaphragm contractile properties. In DEM + RB rats, however, there was a significant decrease in maximum tetanic tension, twitch tension, and tetanic tension. These data reveal that DEM produced an acute depletion of GSH in the diaphragm without impairment of the muscle in nonstressed rats. In the presence of DEM-induced GSH depletion, RB did result in marked diaphragm impairment. The depletion of GSH and the subsequent impairment in diaphragm contractility after RB suggest that GSH may play an important role in protecting the diaphragm against oxidative stress associated with RB.
Protective role for neuropeptides in acute pulmonary response to acrolein in guinea pigs
Authors: Turner C. R. , Stow R. B. , Talerico S. D. , Christian E. P. , Williams J. C.
Published: December 2017

To determine the potential role of neuropeptides in acrolein-induced airway responses, capsaicin-treated guinea pigs were exposed to acrolein aerosol in a regimen causing increased airway sensitivity to substance P. Acrolein exposure resulted in 100% mortality after capsaicin pretreatment compared with only 14% mortality in guinea pigs not pretreated with capsaicin. Acrolein exposure by itself caused marked pulmonary inflammation and large airway epithelial necrosis and denudation. Pretreatment with capsaicin exacerbated these responses throughout the lung. Intravenous acrolein caused an acute dose-related bronchoconstriction in naive guinea pigs that was diminished by capsaicin treatment and potentiated by thiorphan pretreatment, which suggests that arolein exposure causes an acute release of capsaicin-sensitive C-fiber neuropeptides. To determine whether acrolein-induced C-fiber release altered neuronal viability, either rhodamine or Fast Blue dye was instilled intratracheally into vehicle- or acrolein-exposed guinea pigs. Acrolein exposure did not reduce the neuronal uptake or retrograde transport of these dyes, as indicated by the number of fluorescent cell bodies in the nodose ganglia. To determine the functional state of airway neurons, the dose response to intravenous capsaicin was measured in vehicle-exposed and acrolein-exposed guinea pigs; no differences were observed. Thus, acrolein appears to activate airway C-fibers, which release neuropeptides that are protective against this insult, with no suggestion of an accompanying reduction in C-fiber function.
Resting metabolic rate is lower in women than in men
Authors: Arciero P. J. , Goran M. I. , Poehlman E. T.
Published: December 2017

This study examined gender differences in resting metabolic rate (RMR) across a broad age spectrum after controlling for differences in body composition and aerobic fitness. Three hundred twenty-eight healthy men (17–80 yr) and 194 women (18–81 yr) volunteers were characterized for RMR, body composition, physical activity, peak oxygen consumption (peak VO2), anthropometrics, and energy intake. Measured RMR was 23% higher (P < 0.01) in men (1,740 +/- 194 kcal/day) than in women (1,348 +/- 125 kcal/day). Multiple regression analysis showed that 84% of individual variation in RMR was explained by fat-free mass, fat mass, peak VO2, and gender. After controlling for differences in fat-free mass, fat mass, and peak VO2, a lower RMR (3%; P < 0.01) persisted in women (1,563 +/- 153 kcal/day) compared with men (1,613 +/- 127 kcal/day). Adjusted RMR in premenopausal (P < 0.01) and postmenopausal (P < 0.05) women was lower than in men of a similar age. Our results support a lower RMR in women than in men that is independent of differences in body composition and aerobic fitness.
Pulmonary transvascular fluid flux and cardiovascular function in sheep with chronic sepsis
Authors: Nakazawa H. , Noda H. , Noshima S. , Flynn J. T. , Traber L. D. , Herndon D. N. , Traber D. L.
Published: December 2017

We studied the mechanisms responsible for the changes in lung lymph flow (QL) in chronic sepsis induced by the continuous infusion of endotoxin [lipopolysaccharide (LPS), 10 ng.kg-1.min-1]. Sheep (n = 11) were studied in the unanesthetized state 7 days after preparation, and cardiopulmonary variables were measured. In the control group (n = 5) given lactated Ringer solution, no significant changes were observed in any measured variables. In the LPS group (n = 6), QL increased from 11.7 +/- 3.8 to 54.0 +/- 15.0 (SE) ml/h 24 h after LPS infusion had begun. This elevation in QL was associated with little or no change (P > 0.05) in reflection coefficient (0.80 +/- 0.03 to 0.87 +/- 0.05) or pulmonary microvascular pressure (14.3 +/- 0.4 to 16.7 +/- 1.2 mmHg). The filtration coefficient, however, was significantly elevated (0.018 +/- 0.006 to 0.083 +/- 0.024 ml.min-1.mmHg-1). In association with changes in QL that occur as a result of LPS administration, there was a significant increase in cardiac index (6.1 +/- 0.5 to 10.2 +/- 0.3 l.min-1.m-2) and a reduction in mean arterial pressure (90.2 +/- 4.4 to 73.7 +/- 7.3 mmHg) and systemic vascular resistance index (1,229 +/- 134 to 583 +/- 62 dyn.s.cm-5.m2), findings similar to those noted in septic humans.
Partial liquid breathing with perflubron improves arterial oxygenation in acute canine lung injury
Authors: Curtis S. E. , Peek J. T. , Kelly D. R.
Published: December 2017

Tidal liquid breathing with perfluorocarbon liquid improves lung mechanics and gas exchange in surfactant-deficient lambs. We asked whether an intratracheal dose of perflubron equal to liquid functional residual capacity (FRC) or less (partial liquid breathing) would alter gas exchange in gas-ventilated, anesthetized, and oleic acid (OA)-injured dogs. We gave eight dogs perflubron in six aliquots, each equal to one-sixth of liquid FRC [sequential dose (SEQ) group], starting 90 min after OA. Two other groups of eight dogs each received a liquid FRC dose of perflubron (60–70 ml/kg) either just before (P-Pre) or 90 min after (P-Post) OA, and eight control (CON) dogs received OA but no perflubron. In CON, SEQ, and P-Post dogs, OA caused a significant decrease in static respiratory system compliance (Crs) (1.50 +/- 0.05 to 1.15 +/- 0.06 ml.cmH2O–1.kg-1) and arterial PO2 (508 +/- 10 to 113 +/- 16 Torr) by minute 90. In P-Pre, P-Post, and after the third dose of perflubron (50% FRC) in SEQ dogs, arterial PO2 was significantly higher than that in the CON dogs but was similar to that in the CON dogs after perflubron removal. Perflubron doses less than two-thirds of liquid FRC were associated with increased Crs compared with CON dogs, but further lung filling caused a decrease in Crs. Lung histology showed widespread edema and hemorrhage and was similar in perflubron and CON dogs. O2 delivery and uptake were well maintained in all four groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Capsaicin pretreatment attenuates monocrotaline-induced ventilatory dysfunction and pulmonary hypertension
Authors: Zhou K. R. , Lai Y. L.
Published: December 2017

In view of bronchoconstrictor and proliferative effects of tachykinins (TKs; mainly substance P and neurokinin A), as well as increased TK release during tissue injury, we hypothesized that monocrotaline (MCT)-induced ventilatory dysfunction and pulmonary hypertension may be mediated via TKs. In phase 1 of the study (n = 19 rats), we tested and found that elevated lung substance P level and suppressed neutral endopeptidase activity occurred 1–2 wk post-MCT (60 mg/kg sc). Both phase 2 (n = 32) and phase 3 (n = 32) young Sprague-Dawley rats were divided into five groups: control, sham, capsaicin, MCT, and capsaicin + MCT. Rats in the control group received no treatment. Each sham rat received the vehicles. Chronic capsaicin treatment was used to deplete neuropeptides. Each MCT rat received a single injection of MCT 1 wk (phase 2) or 3 wk (phase 3) before the functional study. Each capsaicin + MCT rat received the MCT administration 3 days after the completion of capsaicin pretreatment. In the MCT group, there were significant decreases in dynamic compliance, quasi-static compliance, and the maximal expiratory flow rate at 50% total lung capacity in phase 2, which was accompanied by significant increases in pulmonary arterial pressure, the weight ratio of right ventricle/(left ventricle + septum), and the arterial medial wall thickness in phase 3. In the capsaicin + MCT group, however, all the above MCT-induced changes were significantly attenuated or abolished. All values from the sham and capsaicin groups were not significantly different from those of the control group. These data demonstrate that MCT induces pneumotoxicity, accompanied by elevated levels of substance P in the lung.(ABSTRACT TRUNCATED AT 250 WORDS)
Displacements and strains in the costal diaphragm of the dog
Authors: Boriek A. M. , Wilson T. A. , Rodarte J. R.
Published: December 2017

Radiopaque markers were attached at 1- to 2-cm intervals along three nearby muscle bundles to cover rectangular regions of the mid-costal diaphragms of seven dogs. The markers were tracked by biplane video fluoroscopy during spontaneous breathing (SB), mechanical ventilation with the same tidal volume (MV), and at inflation to total lung capacity (TLC) in the prone and supine positions. The three-dimensional positions of the markers at functional residual capacity (FRC), at end inspiration during SB and MV, and at TLC were determined, and the strains in the plane of the diaphragm relative to FRC were calculated. The principal strains were found to lie nearly along the muscle bundle direction and perpendicular to it. The principal strains along the muscle bundles, which describe muscle shortening, were uniform among the three bundles and uniform along the bundle for MV. For SB, in the prone and supine positions, shortening was approximately 30% greater in the middle of the bundle than near the central tendon and chest wall. Although the tidal volumes were the same for SB and MV, the shortening was larger for SB. The strains perpendicular to the bundle direction were not significantly different from zero. It appears that, for the loads that occur during tidal breathing, the diaphragm is inextensible in the direction perpendicular to the muscle direction. There is a very small displacement of the costal diaphragm at its insertion on the chest wall. The displacement at the central tendon is primarily a result of muscle shortening and rotation of the arc of the muscle around its insertion on the chest wall.
Fluid-regulating and sympathoadrenal hormonal responses to peak exercise following cardiac transplantation
Authors: Perrault H. , Melin B. , Jimenez C. , Dureau G. , Dureau P. , Allevard A. M. , Cottet-Emard J. M. , Gauquelin G. , Gharib C.
Published: December 2017

Orthotopic heart transplantation results in cardiac denervation that can disrupt the normal regulation of hydromineral balance. This study compared the exercise-induced variations in plasma osmolality; atrial natriuretic peptide (ANP), arginine vasopressin (AVP), norepinephrine (NE), epinephrine (E), and dopamine (DA) concentrations; and plasma renin activity (PRA) of six cardiac transplant recipients (HTX) and six healthy age-matched controls (C) submitted to graded upright maximal cycling. Venous blood samples were obtained at rest, at submaximal (70% O2 uptake) and peak exercise, and after 10 and 30 min of sitting recovery. Peak O2 uptake was not different between groups despite lower maximal heart rate in HTX (136 +/- 6 vs. 183 +/- 9 beats/min). Baseline plasma ANP and PRA were higher in HTX (203 +/- 55 pg/ml and 29.9 +/- 7.4 ng.ml-1 x h-1) than in C (71 +/- 17 pg/ml and 5.4 +/- 0.96 ng.ml-1 x h-1); AVP was lower in HTX than in C (1.1 +/- 0.3 vs. 3.2 +/- 0.8 pg/ml; P < 0.05); and circulating E, NE, and DA were not different between groups. Exercise resulted in more marked increases in HTX than in C for ANP (300 vs. 100%), AVP (2,000 vs. 300%), NE (860 vs. 500%), and DA (611 vs. 187%) but not for PRA and a higher E response in C than in HTX (455 vs. 1,258%). These observations confirm that the potential for ANP release to central volume loading is independent of intact cardiac innervation. The exaggerated AVP response in HTX could, however, reflect the absence of inhibitory influences consecutive to denervation.(ABSTRACT TRUNCATED AT 250 WORDS)
Loss of endothelium-dependent vasodilation in the pulmonary vessels of sheep after prolonged endotoxin
Authors: Spath J. A. , Sloane P. J. , Gee M. H. , Albertine K. H.
Published: December 2017

We examined the hemodynamic response of awake sheep to prolonged endotoxin infusion (10 ng.kg-1 x min-1 for 12 h) and the in vitro endothelium-dependent relaxation of pulmonary arterial vessels excised 12 h after the end of endotoxin infusion to determine whether the development of pulmonary hypertension after endotoxin is associated with loss of endothelium-dependent relaxation. In seven of nine sheep, there was a maintained increase (4–68% of baseline) in pulmonary arterial pressure 24 h after the beginning of endotoxin infusion. The greater the increase in pulmonary arterial pressure in vivo, the greater was the in vitro deficit in endothelium-dependent relaxation of the pulmonary vessels. The maximum in vitro vessel dilation was 59% for pulmonary artery rings isolated from sheep without a sustained increase in pulmonary arterial pressure 24 h after endotoxin. Prolonged endotoxin infusion did not alter the in vitro response of pulmonary arterial vessels to KCl or 10(-5) M norepinephrine. Force development, response to 10(-5) M norepinephrine, and vasodilation in response to acetylcholine were also not altered in pulmonary vessels taken from control sheep and exposed in vitro to tumor necrosis factor-alpha (400 U/ml). Our results suggest that loss of endothelium-dependent relaxation in pulmonary vessels supports the sustained pulmonary hypertension that develops after prolonged exposure to endotoxin.
Relative narcotic potency and mode of action of sulfur hexafluoride and nitrogen in humans
Authors: Ostlund A. , Linnarsson D. , Lind F. , Sporrong A.
Published: December 2017

Impairments of psychomotor, perceptual, and cognitive abilities were determined in nine male subjects exposed to inhaled SF6 partial pressures of 0, 52, 104, and 156 kPa and to inhaled N2 partial pressures of 103, 575, 825, and 1,075 kPa. Also data from a previous study with inhaled N2O partial pressures of 0, 13, 26, and 39 kPa were included. With the highest gas concentrations, performances were reduced by 41–57%. Effective doses for a 20% performance impairment were 830, 97, and 21.5 kPa for N2, SF6, and N2O, respectively, yielding relative narcotic potencies of 1.0:8.5:39. The order of narcotic potencies is the same as for the lipid solubility of the three gases. In contrast, the order of increasing tendency for hydrate formation (decreasing hydrate dissociation pressure) for the three gases is N2, N2O, and SF6. Thus, mild to moderate inert gas narcosis in humans shows the same positive relationship to lipid solubility as was shown in previous animal models that utilized much deeper levels of anesthesia.
Modeling methodology for vascular input impedance determination and interpretation
Authors: Bennett S. H.
Published: December 2017

The significance of pulse wave reflections in the pulmonary vascular system is elaborated using a new method to determine the broadband frequency response of input impedance up to frequencies of 100 Hz. A simple data model, based on the signal construct of a wavelet, is used to generalize and reconcile the common approaches to vascular frequency response estimation so that an accurate response can be calculated from physiological waveforms. Input impedance interpretation is accomplished using a structural and functional modeling methodology. To identify internal structural system properties, the methodology of inverse scattering is used to relate observed pulse wave echoes in the frequency response to a longitudinal distribution of reflection sites of anatomic significance. To identify functional interactions with pulmonary vascular wave mechanics, a time series analysis methodology is proposed to describe vascular interactions using a generalized principle of superposition. The methods of determination and interpretation are applied to a sample pressure-flow data set from the pulmonary circulation of a lamb experiencing vascular-ventilatory interaction. The example suggests that the frequency response is consistent with a discrete longitudinal distribution of reflection sites that may be affected by the ventilator.
Three-dimensional reconstruction of the in vivo human diaphragm shape at different lung volumes
Authors: Gauthier A. P. , Verbanck S. , Estenne M. , Segebarth C. , Macklem P. T. , Paiva M.
Published: December 2017

The ability of the diaphragm to generate pressures at different lung volumes (VLs) in humans may be determined by the following factors: 1) its in vivo three-dimensional shape, radius of curvature, and tension according to Laplace law; 2) the relative degree to which it is apposed to the rib cage (i.e., zone of apposition) and lungs (i.e., diaphragm dome); and 3) its length-force properties. To gain more insight into these factors we have reconstructed from nuclear magnetic images the three-dimensional shape of the diaphragm of four normal subjects under supine relaxed conditions at four different VLs: residual volume, functional residual capacity, functional residual capacity plus one-half of the inspiratory capacity, and total lung capacity. Under our experimental conditions the shape of the diaphragm changes substantially in the anteroposterior plane but not in the coronal one. Multivariate regression analysis indicates that the zone of apposition is dependent on both diaphragm shortening and lower rib cage widening with lung inflation, although much more on the first of these two factors. Because of the changes in anteroposterior shape and expansion of the insertional origin at the costal margin with lung inflation, the data therefore suggest that the diaphragm may be more accurately modeled by a “widening piston” (Petroll's model) than a simple “piston in a cylinder” model. A significant portion of the muscular surface is lung apposed, suggesting that diaphragmatic force has radial vectors in the dome and vectors along the body axis in the zone of apposition. The muscular surface area of the diaphragm decreased linearly by approximately 41% with VL from residual volume to total lung capacity. Diaphragmatic fibers may shorten under physiological conditions more than any other skeletal muscle. The large changes in fiber length combined with limited shape changes with lung inflation suggest that the length-twitch force properties of the diaphragm may be the most important factor for the pressure-generating function of this respiratory muscle in response to bilateral phrenic shocks at different VLs.
Cardiac and plasma atrial natriuretic peptide after 9-day hindlimb suspension in rats
Authors: Fareh J. , Bayard B. , Gabrion J. , Thibault G. , Oliver J. , Bouille C. , Gauquelin G. , Gharib C.
Published: December 2017

To determine atrial natriuretic peptide (ANP) adaptation to simulated weightlessness, immunoreactive plasma (ir-NH2- and ir-COOH-terminals) and atrial (ir-COOH-terminal) ANP levels, atrial mRNA expression, immunoreactive cardiocyte ANP levels (ir-NH2- and ir-COOH-terminals), and ultrastructural observations of granules in atrial cardiocytes were assessed in male Wistar rats after a 9-day hindlimb suspension. Plasma ir-NH2- and ir-COOH-terminal ANP concentrations decreased by 17 (P < 0.05) and 37% (P < 0.05), respectively, in suspended rats. A concomitant ir-COOH-terminal ANP content reduction was also observed in left (31%; P < 0.01) and right atria (25%; P < 0.05). Atrial ANP mRNA expression was severely depleted in the right atrium and less so in the left atrium after 9 days of hindlimb suspension. Immunocytochemistry observations demonstrated lowered NH2- and COOH-terminal ANP immunoreactivities in left and right atria from suspended rats. A reduced number of storage granules (dense granules) in both atria was also noted on ultrastructural analysis. It was concluded that ANP biosynthesis, storage, and release were decreased after a 9-day hindlimb suspension.
Coordination between respiration and swallowing: respiratory phase relationships and temporal integration
Authors: Martin B. J. , Logemann J. A. , Shaker R. , Dodds W. J.
Published: December 2017

The coordination of breathing and swallowing was studied in 13 young healthy adult subjects during the administration of graduated volumes of water (3, 10, and 20 ml). Simultaneous submental electromyography, respiratory plethysmography, and fiber-optic endoscopy revealed a well-timed pattern between physiological respiratory events and related swallowing events. Expiration was the phase of respiration that was most closely associated with deglutition. Respiration was usually maintained at the onset of deglutition and halted before the onset of laryngeal elevation. The apneic interval was approximately 1 s for the 3-, 10-, and 20-ml boluses. A large-volume (100-ml) straw swallow resulted in variable respiration-swallowing patterns and in statistically significant differences (P < 0.01) in the duration of apneic pause and laryngeal excursion. The expiratory phase of respiration resumed nearly 0.50 s before the completion of swallowing. Clinical implications of the findings are addressed and related to aspiration and pulmonary complications in dysphagic patients.
Severe VA/Q mismatch in perfused lungs evoked by sequential challenge with endotoxin and E. coli hemolysin
Authors: Walmrath D. , Pilch J. , Scharmann M. , Grimminger F. , Seeger W.
Published: December 2017

Escherichia coli hemolysin (ECH), an important pathogenicity factor in extraintestinal E. coli infections, provokes pulmonary hypertension and microvascular leakage in buffer-perfused rabbit lungs. We investigated gas exchange abnormalities in response to low doses of ECH, lipopolysaccharides (LPS), and sequential and combined application of these bacterial agents by using the multiple inert gas elimination technique. In control lungs and after admixture of 100 ng/ml of LPS, unimodal narrow distribution of perfusion and ventilation to midrange ventilation-perfusion (VA/Q) areas was noted. ECH [0.08 hemolytic units (HU)/ml] caused a moderate increase in pulmonary arterial pressure (< 10 mmHg), progressive lung edema formation (approximately 10 g within 20 min), and a broadening of perfusate and gas flow dispersion. Application of 0.08 HU/ml of ECH in lungs “primed” with 100 ng/ml of LPS in a preceding 125-min perfusion period provoked a large increase in pulmonary arterial pressure (> 50 mmHg within 5 min), rapid edema formation (approximately 10 g within 10 min), and severe VA/Q mismatch with predominance of shunt flow. Vasoconstrictor response and VA/Q mismatch, but not edema formation, were largely inhibited by pretreatment of lungs with acetylsalicylic acid or the thromboxane receptor antagonist BM-13.505. In addition, “rescue” application of BM-13.505 rapidly reversed pressure rise and shunt flow due to sequential LPS and/or ECH stimulation, whereas edema formation was not affected. We conclude that the marked pulmonary hypertension in response to low doses of ECH in LPS-primed lungs is paralleled by severe gas exchange abnormalities with predominance of shunt flow. Both the vasoconstrictor response and the development of shunt are closely related to toxin-induced thromboxane generation.
Decrease in left ventricular contractility after tumor necrosis factor-alpha infusion in dogs
Authors: Walley K. R. , Hebert P. C. , Wakai Y. , Wilcox P. G. , Road J. D. , Cooper D. J.
Published: December 2017

Whether systolic contractility or diastolic compliance changes soon after tumor necrosis factor-alpha (TNF-alpha) exposure is not known. Accordingly, we measured hemodynamics, left ventricular contractility using the slope of the end-systolic pressure-volume relationship, and diastolic pressure-volume relationships in six control dogs and in six dogs receiving 60 micrograms.kg-1.h-1 i.v. of TNF-alpha. Mean aortic pressure decreased by 22% 1 h after TNF-alpha infusion and remained decreased (P < 0.05). Cardiac output increased by 19% 1 h after TNF-alpha infusion and remained significantly greater than control values (P < 0.05). Left ventricular contractility decreased by 23% (P < 0.05) 1 h after TNF-alpha infusion and decreased by 52% (P < 0.01) 5 h after TNF-alpha infusion. The diastolic pressure-volume relationship did not change in the TNF-alpha group or the control group. Ejection fraction did not change after TNF-alpha infusion despite the decrease in contractility because afterload decreased. We conclude that TNF-alpha is important in causing the hypotensive, hyperdynamic circulation of sepsis. The new finding that left ventricular contractility is decreased shortly after TNF-alpha infusion suggests that TNF-alpha, or another mediator released very soon after TNF-alpha, is an important myocardial depressant factor.
Role of N-methyl-D-aspartate receptors in the pontine pneumotaxic mechanism in the cat
Authors: Ling L. , Karius D. R. , Speck D. F.
Published: December 2017

Systemic injection of MK-801, an N-methyl-D-aspartate (NMDA) receptor-associated channel blocker, induces an apneusis in vagotomized cats similar to that produced by pontine respiratory group (PRG) lesions, suggesting the possible involvement of NMDA receptors in the pontine pneumotaxic mechanism. Previous results from our laboratory indicate that the efferent limb of the pontine pneumotaxic mechanism is unlikely to require NMDA receptor-mediated neurotransmission. Therefore, the present study examined the potential involvement of PRG NMDA receptors in the pontine pneumotaxic mechanism. Experiments were conducted in decerebrate, paralyzed, and ventilated adult cats. The effects on inspiratory time (TI) of MK-801 microinjection into PRG were tested in 12 cats. Pressure microinjection of MK-801 (15 mM, 80–3,000 nl) significantly prolonged TI in all animals when lung inflation was withheld. TI progressively increased in most animals for > or = 30 min. After this period, partial recovery of the effect occurred in eight cats as TI shortened toward predrug levels. In three animals, microinjection of MK-801 induced a complete apneusis in the absence of lung inflation from which there was no detectable recovery. Microinjections into regions approximately 2 mm distant from PRG produced little or no effect. These results provide evidence that NMDA receptors located in the region of PRG play an important functional role in the control of the breathing cycle.
Myosin and actin filament lengths in diaphragms from emphysematous hamsters
Authors: Poole D. C. , Lieber R. L. , Mathieu-Costello O.
Published: December 2017

In vitro studies of the diaphragm from emphysematous animals have, in some instances, shown an alteration in its sarcomere length-tension relationship and a decreased maximal specific tension. To our knowledge, it has never been determined whether such functional changes may be indicative of ultrastructural adaptations, e.g., changes in filament lengths and thus cross-bridge number. To address this, we compared filament lengths in diaphragms from hamsters in which emphysema was induced by endotracheal instillation of elastase (E) 5 mo before the hamsters were killed with those from control hamsters (C; saline instillation). Diaphragms were then fixed by vascular perfusion with buffered glutaraldehyde in situ at airway pressures set to approximate the physiological range of lung volumes from residual volume (RV) to total lung capacity (TLC). Ultrathin sections (50–70 nm) were taken parallel to the muscle fiber axis and examined by electron microscopy (x33,000). Sarcomere and filament length measurements were calibrated using an actin periodicity of 39 nm and an M-band width of 86 nm to correct for dimensional changes during preparation. Emphysema increased the change in lung volume from -20 to +25 cmH2O airway pressure (from RV to TLC) by approximately 88%, and the displacement volume of excised lung at 0 cmH2O airway pressure was increased by approximately 138% on average. Neither myosin (C = 1.592 +/- 0.027; E = 1.572 +/- 0.035 micron; P = 0.72) nor actin (C = 1.210 +/- 0.035; E = 1.221 +/- 0.014 micron; P = 0.76) filament lengths were affected by emphysema. Thus, filament length changes do not underlie the diaphragm functional adaptations observed previously in emphysema.