Effect of amiloride in human and sheep parietal pleura

The fluid and solute transport properties of human parietal pleura were studied and compared with sheep parietal pleura in vitro. The pleura was mounted as a planar sheet between Ussing-type chambers. The results presented are the mean values of nine different experiments. The transepithelial electrical resistance (R(TE)) of both pleurae species was measured before and after the addition of amiloride in both sides of pleura. The R(TE) for human was 25.74 +/- 1.23 Ohm x cm(2), while for the sheep it was 38.18 +/- 0.83 Ohm x cm(2). The addition of amiloride to the serosal bathing solution increased the R(TE) of human pleura to 30.48 +/- 1.01 Ohm x cm(2) and sheep pleura to 40.32 +/- 0.82 Ohm x cm(2), while amiloride had no effect on the basolateral side. From the above, it is strongly suggested that the human pleura seems to be more leaky than sheep pleura. Although the R(TE) was increased in both pleurae, the elevation in human pleura was significantly higher, thus results from experiments in sheep pleura could only partly be extrapolated in human pleura.     

Reproducibility of twitch and sniff transdiaphragmatic pressures

Twitch transdiaphragmatic pressure (Tw Pdi) measured with magnetic stimulation of the phrenic nerve is used to follow up patients and to assess the effect of clinical treatments on diaphragm function. However the reproducibility of Tw Pdi on different occasions has been little studied. We investigated 32 normal subjects, measuring Tw Pdi elicited by bilateral magnetic stimulation of the phrenic nerves on two to 14 occasions. Sniff transdiaphragmatic pressure (sniff Pdi) was also measured. The mean value of Tw Pdi and sniff Pdi were 28+/-5 and 134+/-24 cm H(2)O, respectively. The within subjects coefficient of variation was 11% for both Tw Pdi and sniff Pdi. We conclude that there is a variability of Tw Pdi and the variability of Tw Pdi is the same as that of sniff Pdi.     

The post-exercise oxidative stress is depressed by acetylsalicylic acid

In order to assess whether oxidative stress occurs after fatiguing dynamic contractions of a small forearm muscle group, we estimated the kinetics of changes in some of its biomarkers (thiobarbituric acid reactive substances or TBARS; plasma reduced ascorbic acid or RAA; erythrocyte reduced glutathione or GSH). We also tested the hypothesis that acetylsalicylic acid (ASA) may compete with endogenous radical targets, attenuating the post-exercise oxidative stress. Seven male subjects successively performed a 3-min dynamic handgrip exercise with the dominant and then the contralateral forearm. Blood samples were taken from an antecubital vein in each exercising forearm. Biochemical analyses, including the concentration measurements of lactic acid, potassium, and oxidative stress markers were performed at rest and then during the 30-min period of recovery following each exercise. The same day, exercises were repeated after ingestion of a single dose (10 mg/kg) of ASA, and the same exercises were performed after a 3-day ASA treatment (30 mg/kg/day). In control condition, the changes in TBARS, RAA and GSH were already significant immediately after the end of the forearm exercise. They culminated after 5 min, and control values were recovered by a 30-min rest period. We verified that repeated bouts failed to alter the post-exercise variations. ASA did not modify the lactic acid production significantly, though the 3-day ASA treatment significantly reduced the efflux of potassium (-74%, P < 0.05), and the post-exercise variations of TBARS (-45%, P < 0.01), RAA (-44%, P < 0.01) and GSH (-48%, P < 0.01). These results suggest that the dynamic handgrip exercise is a good model for studying the post-exercise oxidative stress and also that ASA seems to offer an efficient protection against oxidative stress and the changes in membrane permeability to potassium.     

Respiratory influences on sympathetic vasomotor outflow in humans

We have attempted to synthesize findings dealing with four types of respiratory system influences on sympathetic outflow in the human. First, a powerful lung volume-dependent modulation of muscle sympathetic nerve activity (MSNA) occurs within each respiratory cycle showing late-inspiratory inhibition and late-expiratory excitation. Secondly, in the intact human, neither reductions in spontaneous respiratory motor output nor voluntary near-maximum increases in central respiratory motor output and inspiratory effort, per sec, influence MSNA modulation within a breath, MSNA total activity or limb vascular conductance. Thirdly, carotid chemoreceptor stimuli markedly increase total MSNA; but most of the MSNA response to chemoreceptor activation appears to be mediated independently of increased central respiratory motor output. Fourthly, repeated fatiguing contractions of the diaphragm or expiratory muscles in the human show a metaboreflex mediated time-dependent increase in MSNA and reduced vascular conductance and blood flow in the resting limb. Recent evidence suggests that these respiratory influences contribute significantly to sympathetic vasomotor outflow and to the distribution of systemic vascular conductances and blood flow in the exercising human.     

Usefulness of phrenic nerve stimulation to measure upper airway collapsibility in normal awake subjects

Upper airway (UA) collapsibility can be characterized during sleep by looking at the changes in inspiratory flow limitation (IFL) with changing nasal pressure. IFL can be induced during wakefulness using phrenic nerve stimulation (PNS) applied during exclusive nasal breathing. The aim of the study was to evaluate the possibility of measuring UA critical pressure (Pcrit) in normal awaked subjects using electrical PNS (EPNS) or bilateral anterior magnetic phrenic stimulation (BAMPS). Instantaneous flow, esophageal (Peso) and mask pressures (Pmask), and genioglossal (GG) end-expiratory EMG activity were recorded in 13 normal subjects (4F, 9M) with randomly changing Pmask (0 to -20 cmH2O). For each trial, we examined the relationship between maximal inspiratory flow (Vtmax) of IFL twitches and the corresponding Pmask. Pcrit could be determined in 12 subjects (mean -33.5 +/- 16.3 cmH2O). No difference in Pcrit values was found between the EPNS and BAMPS methods but the strength of the Vtmax/Pmask relationship was higher with BAMPS. GG end-expiratory EMG activity increased with decreasing Pmask but no significant relationship was found between the slope of the GG end-expiratory EMG activity/Pmask relationship and Pcrit. We conclude that: (1) Pcrit can be measured during wakefulness in normal using PNS: (2) Pcrit measurements may be easier and more reliable with BAMPS than EPNS: and (3) Pcrit does not seem to be influenced by the pressure-related changes in GG end-expiratory EMG.     

Neurochemical perspectives on the control of breathing during sleep

A specific depression of minute ventilation occurs during sleep in normal subjects. This sleep-related ventilatory depression is partially related to mechanical events and upper airway atonia but some data also indicate that it is likely to be centrally mediated. This paper reviews the anatomical and neurochemical connections between sleep/wake- and respiratory-related areas in an attempt to identify the potential implication of sleep-related neurochemicals (serotonin, catecholamines, GABA, acetylcholine) in the sleep-related hypoventilation. The review of available data suggests that the sleep-related ventilatory depression depends upon the enhanced GABAergic activity together with a loss of suprapontine influence depending on the cessation of activity of the reticular formation. During REM sleep, an additional inhibitory activity emerges from the pontine cholinergic neurons, which contributes to the breathing irregularities and the associated depression of minute ventilation and ventilatory response to chemical stimuli. This model may contribute to a better understanding of the neurochemical environment of respiratory neurons during sleep, which remains a question of importance regarding the numerous pathological states that are linked to specific perturbations of breathing control during sleep.     

Prevention of bronchoconstriction in sensitized guinea pigs: efficacy of common prophylactic drugs

Efficacy of beta2-agonists (B2), anticholinergics, corticosteroids, anti-inflammatory drugs or antihistamines against methacholine, histamine, or allergen-induced lung constriction was tested in ovalbumin sensitized guinea pigs. Airway resistance (Raw) and parenchymal damping (G) and elastance (H) were determined from low-frequency forced oscillatory input impedance (ZL). ZL was measured under control conditions, during iv infusions of methacholine, and following iv boluses of histamine or ovalbumin. In decreasing potency, ipratropium, salmeterol, fluticasone or cromoglycate reduced the methacholine-induced increases in Raw and G. Only antihistamines had any effects on the histamine-induced increased in Raw, G, and H. The ovalbumin-induced increases in Raw, G and H in the control animals (120 +/- 90%, 201 +/- 126%, 86 +/- 71%) were markedly reduced by pretreatments with antihistamines (18 +/- 11%, 13 +/- 9%, 3+/- 3%) and cromoglycate (29 +/- 13%, 35 +/- 22%, 18 +/- 10%). Bronchoconstriction induced by muscarinic receptor stimulation is inhibited by anticholinergic, anti-inflammatory or beta2-agonist pretreatment; antihistaminic or anti-inflammatory premedication is beneficial if the release of histamine via an exposure to allergen is responsible for the fall in lung function.     

Pontine respiratory group neuron discharge is altered during fictive cough in the decerebrate cat

A network of neurons in the rostral dorsal lateral pons and pons/mescencephalic junction constitute the pontine respiratory group (PRG) and is essential for reflex cough. As a next step in understanding the role of the PRG in the expression of the cough reflex, we examined neuron firing rates during fictive cough in cats. Decerebrated, thoracotomized, paralyzed, cycle-triggered ventilated adult cats were used. Extracellular activity of many single neurons and phrenic and lumbar neurograms were monitored during fictive cough produced by mechanical stimulation of the intrathoracic trachea. Neurons were tested during control periods for respiratory modulation of firing rate by cycle-triggered histograms and statistical tests. Most respiratory modulated cells were continuously active with various superimposed respiratory patterns; major categories included inspiratory decrementing (I-Dec), expiratory decrementing (E-Dec) and expiratory augmenting (E-Aug). There were alterations in the discharge patterns of respiratory, as well as, non-respiratory modulated neurons during cough. The results suggest an involvement of the PRG in the configuration of the cough motor pattern.     

Effects of inactivation and stimulation of locus coeruleus on respiratory activity of neonatal rat

We examined the effects of pharmacological inactivation and electrical stimulation of the locus coeruleus (LC) on the respiratory rate (RR) in isolated brainstem-spinal cord preparations of the neonatal rat. The brainstem and spinal cord were isolated en bloc from neonatal (days 1-4) Sprague-Dawley rats and superfused with artificial cerebrospinal fluid (ACSF) equilibrated with a gas mixture containing 2% CO(2) (pH 7.8). Pharmacological inactivation of the bilateral LC by means of microinjection of tetrodotoxin or noradrenaline elicited a significant decrease in RR in preparations obtained from rats aged 3-4 days, but not in preparations of rats aged 1-2 days. Stimulation of the bilateral LC with a train of electrical pulses (25-50 microA, 30 ms, 0.5 Hz, 3-4 min) caused a marginal but significant increase in RR on days 3-4, but not on days 1-2. These results indicate that the LC exerts an excitatory effect on the medullary respiratory rhythm generator in an age-dependent manner.     

Oxygen isotope fractionation in healthy subjects and in patients with COPD

We determined the oxygen isotope fractionation degree for oxygen utilized (delta(U)) in expired alveolar gas relative to inspired air in patients with chronic obstructive lung disease (COPD) and, for comparison, in two groups of healthy subjects, old and young. In addition, we determined Delta(rel)R(vent) and Delta(rel)R(tot). These determinants of delta(U) (=Delta(rel)R(tot)-Delta(rel)R(vent)) are related to the oxygen isotope fractionation which occurs in the first part of the O(2) pathway by ventilation of alveolar gas (Delta(rel)R(vent)) and by O(2) transport and utilization in the rest of the O(2) pathway from the alveolar space (Delta(rel)R(tot)). Mean delta(U) values for the three groups of subjects were close: 9.0, 9.0 and 9.9 per thousand, respectively, with no significant differences between groups. Mean Delta(rel)R(vent) for patients with COPD was substantially larger than for young, healthy subjects, 4.0 per thousand versus 0.94 per thousand, with P<10(-3). This result indicates that the contribution of intrapulmonary gas transport by diffusion to Delta(rel)R(vent) is larger for patients with COPD than for young, healthy subjects. Mean Delta(rel)R(tot) for patients with COPD was also larger than for young, healthy subjects, 13.0 per thousand versus 10.84 per thousand, but this difference was not significant (P=0.06). Further, Delta(rel)R(tot) was much larger than Delta(rel)R(vent) for all groups of subjects (P<10(-7)).