Similar ventilation distribution in normal subjects prone and supine during tidal breathing.

Multiple-breath washout (MBW) tests, with end-expiratory lung volume at functional residual capacity (FRC) and 90% O(2), 5% He, and 5% SF(6) as an inspired gas mixture, were performed in healthy volunteers in supine and prone postures. The semilog plot of MBW N(2) concentrations was evaluated in terms of its curvilinearity. The MBW N(2) normalized slope analysis yielded indexes of acinar and conductive ventilation heterogeneity (Verbanck S, Schuermans D, Van Muylem A, Paiva M, Noppen M, and Vincken W. J App Physiol 83: 1907-1916, 1997). Also, the difference between SF(6) and He normalized phase III slopes was computed in the first MBW expiration. Only MBW tests with similar FRC in the prone and supine postures (P > 0.1; n = 8) were considered. Prone and supine postures did not reveal any significant differences in curvilinearity, N(2) normalized slope-derived indexes of conductive or acinar ventilation heterogeneity, nor SF(6)-He normalized phase III slope difference in the first MBW expiration (P > 0.1 for all). The absence of significant changes in any of the MBW indexes suggests that ventilation heterogeneity is similar in the supine and prone postures of normal subjects breathing near FRC.     

Effect of expiratory loading on glottic dimensions in humans

We examined the effects of external mechanical loading on glottic dimensions in 13 normal subjects. When flow-resistive loads of 7, 27, and 48 cmH2O X l-1 X s, measured at 0.2 l/s, were applied during expiration, glottic width at the mid-tidal volume point in expiration (dge) was 2.3 +/- 12, 37.9 +/- 7.5, and 38.3 +/- 8.9% (means +/- SE) less than the control dge, respectively. Simultaneously, mouth pressure (Pm) increased by 2.5 +/- 4, 3.0 +/- 0.4, and 4.6 +/- 0.6 cmH2O, respectively. When subjects were switched from a resistance to a positive end-expiratory pressure at comparable values of Pm, both dge and expiratory flow returned to control values, whereas the level of hyperinflation remained constant. Glottic width during inspiration (unloaded) did not change on any of the resistive loads. There was a slight inverse relationship between the ratio of expiratory to inspiratory glottic width and the ratio of expiratory to inspiratory duration. Our results show noncompensatory glottic narrowing when subjects breathe against an expiratory resistance and suggest that the glottic dimensions are influenced by the time course of lung emptying during expiration. We speculate that the glottic constriction is related to the increased activity of expiratory medullary neurons during loaded expiration and, by increasing the internal impedance of the respiratory system, may have a stabilizing function.     

Protective effect of lung inflation in reperfusion-induced lung microvascular injury

We used the isolated-perfused rat lung model to study the influence of pulmonary ventilation and surfactant instillation on the development of postreperfusion lung microvascular injury. We hypothesized that the state of lung inflation during ischemia contributes to the development of the injury during reperfusion. Pulmonary microvascular injury was assessed by continuously monitoring the wet lung weight and measuring the vessel wall (125)I-labeled albumin ((125)I-albumin) permeability-surface area product (PS). Sprague-Dawley rats (n = 24) were divided into one control group and five experimental groups (n = 4 rats per group). Control lungs were continuously ventilated with 20% O(2) and perfused for 120 min. All lung preparations were ventilated with 20% O(2) before the ischemia period and during the reperfusion period. The various groups differed only in the ventilatory gas mixtures used during the flow cessation: group I, ventilated with 20% O(2); group II, ventilated with 100% N(2); group III, lungs remained collapsed and unventilated; group IV, same as group III but pretreated with surfactant (4 ml/kg) instilled into the airway; and group V, same as group III but saline (4 ml/kg) was instilled into the airway. Control lungs remained isogravimetric with baseline (125)I-albumin PS value of 4.9 +/- 0.3 x 10(-3) ml x min(-1) x g wet lung wt(-1). Lung wet weight in group III increased by 1.45 +/- 0.35 g and albumin PS increased to 17.7 +/- 2.3 x 10(-3), indicating development of vascular injury during the reperfusion period. Lung wet weight and albumin PS did not increase in groups I and II, indicating that ventilation by either 20% O(2) or 100% N(2) prevented vascular injury. Pretreatment of collapsed lungs with surfactant before cessation of flow also prevented the vascular injury, whereas pretreatment with saline vehicle had no effect. These results indicate that the state of lung inflation during ischemia (irrespective of gas mixture used) and supplementation of surfactant prevent reperfusion-induced lung microvascular injury.     

Inhomogeneity during deflation of excised canine lungs. III. Single-breath O2 tests

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

Effects of expiratory resistive loading on the sensation of dyspnea

To determine whether an increase in expiratory motor output accentuates the sensation of dyspnea (difficulty in breathing), the following experiments were undertaken. Ten normal subjects, in a series of 2-min trials, breathed freely (level I) or maintained a target tidal volume equal to (level II) or twice the control (level III) at a breathing frequency of 15/min (similar to the control frequency) with an inspiratory load, an expiratory load, and without loads under hyperoxic normocapnia. In tests at levels II and III, end-expiratory lung volume was maintained at functional residual capacity. A linear resistance of 25 cmH2O.1(-1).s was used for both inspiratory and expiratory loading; peak mouth pressure (Pm) was measured, and the intensity of dyspnea (psi) was assessed with a visual analog scale. The sensation of dyspnea increased significantly with the magnitude of expiratory Pm during expiratory loading (level II: Pm = 9.4 +/- 1.5 (SE) cmH2O, psi = 1.26 +/- 0.35; level III: Pm = 20.3 +/- 2.8 cmH2O, psi = 2.22 +/- 0.48) and with inspiratory Pm during inspiratory loading (level II: Pm = 9.7 +/- 1.2 cmH2O, psi = 1.35 +/- 0.38; level III: Pm = 23.9 +/- 3.0 cmH2O, psi = 2.69 +/- 0.60). However, at each level of breathing, neither the intensity of dyspnea nor the magnitude of peak Pm during loading was different between inspiratory and expiratory loading. The augmentation of dyspnea during expiratory loading was not explained simply by increases in inspiratory activity. The results indicate that heightened expiratory as well as inspiratory motor output causes comparable increases in the sensation of difficulty in breathing.     

Respiratory mechanics during halothane anesthesia and anesthesia-paralysis in humans

In six spontaneously breathing anesthetized subjects [halothane approximately 1 maximum anesthetic concentration (MAC), 70% N2O-30% O2], we measured flow (V), volume (V), and tracheal pressure (Ptr). With airway occluded at end-inspiration tidal volume (VT), we measured Ptr when the subjects relaxed the respiratory muscles. Dividing relaxed Ptr by VT, total respiratory system elastance (Ers) was obtained. With the subject still relaxed, the occlusion was released to obtain the V-V relationship during the ensuing relaxed expiration. Under these conditions, the expiratory driving pressure is V X Ers, and thus the pressure-flow relationship of the system can be obtained. By subtracting the flow resistance of equipment, the intrinsic respiratory flow resistance (Rrs) is obtained. Similar measurements were repeated during anesthesia-paralysis (succinylcholine). Ers averaged 23.9 +/- 4 (+/- SD) during anesthesia and 21 +/- 1.8 cmH2O X 1(-1) during anesthesia-paralysis. The corresponding values of intrinsic Rrs were 1.6 +/- 0.7 and 1.9 +/- 0.9 cmH2O X 1(-1) X s, respectively. These results indicate that Ers increases substantially during anesthesia, whereas Rrs remains within the normal limits. Muscle paralysis has no significant effect on Ers and Rrs. We also provide the first measurements of inspiratory muscle activity and related negative work during spontaneous expiration in anesthetized humans. These show that 36-74% of the elastic energy stored during inspiration is wasted in terms of negative inspiratory muscle work.     

Properties of steady maximal expiratory flow within excised canine central airways

Using our transistor model of the lung during forced expiration (J. Appl. Physiol. 62: 2013-2025, 1987), we recently predicted that 1) axially arranged choke points can exist simultaneously during forced expiration with sufficient effort, and 2) overall maximal expiratory flow may be relatively insensitive to nonuniform airways obstruction because of flow interdependence between parallel upstream branches. We tested these hypotheses in excised central airways obtained from five canine lungs. Steady expiratory flow was induced by supplying constant upstream pressure (Pupstream = 0-16 cmH2O) to the bronchi of both lungs while lowering pressure at the tracheal airway opening (16 to -140 cmH2O). Intra-airway pressure profiles obtained during steady maximal expiratory flow disclosed a single choke point in the midtrachea when Pupstream was high (2-16 cmH2O). However, when Pupstream was low (0 cmH2O), two choke sites were evident: the tracheal site persisted, but another upstream choke point (main carina or both main bronchi) was added. Flow interdependence was studied by comparing maximal expiratory flow through each lung before and after introduction of a unilateral external resistance upstream of the bronchi of one lung. When this unilateral resistance was added, ipsilateral flow always fell, but changes in flow through the contralateral lung depended on the site of the most upstream choke. When a single choke existed in the trachea, addition of the external resistance increased contralateral flow by 38 +/- 28% (SD, P less than 0.003). In contrast, when the most upstream choke existed at the main carina or in the bronchi, addition of the external resistance had no effect on contralateral maximal expiratory flow.(ABSTRACT TRUNCATED AT 250 WORDS)     

New method of respiratory gas analysis: light spectrometer

A multigas concentration analyzer particularly suited for respiratory gas analysis has been developed using a new principle based on the measurement of the intensity of light emitted by excited atoms or ions in a direct current glow discharge. This glow discharge spectral emission gas analyzer (GDSEA), or light spectrometer, simultaneously measures O2, N2, CO2, He, and N2O gas concentrations with a 0-90% response time of 100 ms and a sample rate of less than 20 ml/min in a short gas sample line configuration. Mole accuracy and resolution of the GDSEA using a short sample line were determined in the laboratory to be +/- 0.15 to +/- 0.7% and 0.02-0.05%, respectively. In the clinical setting a comparative evaluation was made with a mass spectrometer in a long sample line, computerized, multibed, respiratory monitoring system. Results indicate a close agreement between the two instruments with differences in mixed inspiratory or expiratory O2 and CO2 concentrations of less than 2% and of derived variables, such as O2 consumption, CO2 production, and respiratory exchange ratio, of less than 5%.     

Effect of experimental hydrothorax on the cough reflex in conscious cats.

The authors induced experimental hydrothorax in cats by injecting dextran into the pleural cavity under brief N2O anaesthesia. They examined the parameters of cough -- elicited by mechanical stimulation of the airway mucosa -- and blood gas and pH values under normal conditions and after the injection of 50, 100, 200 and 250 ml dextran. The tests were always performed 30 min after terminating anaesthesia, i.e. in conscious animals. The free fluid in the thorax was found, in conscious cats, to reduce the inspiratory values of cough, but to have no effect on cough expiration. This is in agreement with previous findings showing that the intensity of a cough expiration does not always depend on the intensity of the preceding cough inspiration. According to this finding, the decrease in the expiratory values of cough observed during experimental pleurisy cannot be due to the actual exudate. In cats, experimental hydrothorax in doses of 200 and 250 ml leads to respiratory insufficiency. The authors further found that, for the study of interoception in the airways of conscious cats, which requires experimental induction of pathological conditions under brief anaesthesia, nitrous oxide is a convenient anesthetic.     

Lung hyperinflation in isolated dog lungs during high-frequency oscillation

To study the phenomenon of lung hyperinflation (LHI), i.e., an increase in lung volume without a concomitant rise in airway pressure, we measured lung volume changes in isolated dog lungs during high-frequency oscillation (HFO) with air, He, and SF6 and with mean tracheal pressure controlled at 2.5, 5.0, and 7.5 cmH2O. The tidal volume and frequency used were 1.5 ml/kg body wt and 20 Hz, respectively. LHI was observed during HFO in all cases except for a few trials with He. The degree of LHI was inversely related to mean tracheal pressure and varied directly with gas density. Maximum expiratory flow rate (Vmax) was measured during forced expiration induced by a vacuum source (-150 cmH2O) at the trachea. Vmax was consistently higher than the peak oscillatory flow rate (Vosc) during HFO, demonstrating that overall expiratory flow limitation did not cause LHI in isolated dog lungs. Asymmetry of inspiratory and expiratory impedances seems to be one cause of LHI, although other factors are involved.     

Mode shift of an inhaled aerosol bolus is correlated with flow sequencing in the human lung.

We studied the effects on aerosol bolus inhalations of small changes in convective inhomogeneity induced by posture change from upright to supine in nine normal subjects. Vital capacity single-breath nitrogen washout tests were used to determine ventilatory inhomogeneity change between postures. Relative to upright, supine phase III slope was increased 33 +/- 11% (mean +/- SE, P < 0.05) and phase IV height increased 25 +/- 11% (P < 0.05), consistent with an increase in convective inhomogeneity likely due to increases in flow sequencing. Subjects also performed 0.5-microm-particle bolus inhalations to penetration volumes (V(p)) between 150 and 1,200 ml during a standardized inhalation from residual volume to 1 liter above upright functional residual capacity. Mode shift (MS) in supine posture was more mouthward than upright at all V(p), changing by 11.6 ml at V(p) = 150 ml (P < 0.05) and 38.4 ml at V(p) = 1,200 ml (P < 0.05). MS and phase III slope changes correlated positively at deeper V(p). Deposition did not change at any V(p), suggesting that deposition did not cause the MS change. We propose that the MS change results from increased sequencing in supine vs. upright posture.     

Determinants of exercise performance in normal men with externally imposed expiratory flow limitation.

To understand how externally applied expiratory flow limitation (EFL) leads to impaired exercise performance and dyspnea, we studied six healthy males during control incremental exercise to exhaustion (C) and with EFL at approximately 1. We measured volume at the mouth (Vm), esophageal, gastric and transdiaphragmatic (Pdi) pressures, maximal exercise power (W(max)) and the difference (Delta) in Borg scale ratings of breathlessness between C and EFL exercise. Optoelectronic plethysmography measured chest wall and lung volume (VL). From Campbell diagrams, we measured alveolar (PA) and expiratory muscle (Pmus) pressures, and from Pdi and abdominal motion, an index of diaphragmatic power (W(di)). Four subjects hyperinflated and two did not. EFL limited performance equally to 65% W(max) with Borg = 9-10 in both. At EFL W(max), inspiratory time (TI) was 0.66s +/- 0.08, expiratory time (TE) 2.12 +/- 0.26 s, Pmus approximately 40 cmH2O and DeltaVL-DeltaVm = 488.7 +/- 74.1 ml. From PA and VL, we calculated compressed gas volume (VC) = 163.0 +/- 4.6 ml. The difference, DeltaVL-DeltaVm-VC (estimated blood volume shift) was 326 ml +/- 66 or 7.2 ml/cmH2O PA. The high Pmus and long TE mimicked a Valsalva maneuver from which the short TI did not allow recovery. Multiple stepwise linear regression revealed that the difference between C and EFL Pmus accounted for 70.3% of the variance in DeltaBorg. DeltaW(di) added 12.5%. We conclude that high expiratory pressures cause severe dyspnea and the possibility of adverse circulatory events, both of which would impair exercise performance.     

Effects of augmented respiratory muscle pressure production on locomotor limb venous return during calf contraction exercise.

We determined effects of augmented inspiratory and expiratory intrathoracic pressure or abdominal pressure (Pab) excursions on within-breath changes in steady-state femoral venous blood flow (Qfv) and net Qfv during tightly controlled (total breath time = 4 s, duty cycle = 0.5) accessory muscle/"rib cage" (DeltaPab <2 cmH2O) or diaphragmatic (DeltaPab >5 cmH2O) breathing. Selectively augmenting inspiratory intrathoracic pressure excursion during rib cage breathing augmented inspiratory facilitation of Qfv from the resting limb (69% and 89% of all flow occurred during nonloaded and loaded inspiration, respectively); however, net Qfv in the steady state was not altered because of slight reductions in femoral venous return during the ensuing expiratory phase of the breath. Selectively augmenting inspiratory esophageal pressure excursion during a predominantly diaphragmatic breath at rest did not alter within-breath changes in Qfv relative to nonloaded conditions (net retrograde flow = -9 +/- 12% and -4 +/- 9% during nonloaded and loaded inspiration, respectively), supporting the notion that the inferior vena cava is completely collapsed by relatively small increases in gastric pressure. Addition of inspiratory + expiratory loading to diaphragmatic breathing at rest resulted in reversal of within-breath changes in Qfv, such that >90% of all anterograde Qfv occurred during inspiration. Inspiratory + expiratory loading also reduced steady-state Qfv during mild- and moderate-intensity calf contractions compared with inspiratory loading alone. We conclude that 1) exaggerated inspiratory pressure excursions may augment within-breath changes in femoral venous return but do not increase net Qfv in the steady state and 2) active expiration during diaphragmatic breathing reduces the steady-state hyperemic response to dynamic exercise by mechanically impeding venous return from the locomotor limb, which may contribute to exercise limitation in health and disease.     

Effect of negative expiratory pressure on respiratory system flow resistance in awake snorers and nonsnorers.

In spontaneously breathing subjects, intrathoracic expiratory flow limitation can be detected by applying a negative expiratory pressure (NEP) at the mouth during tidal expiration. To assess whether NEP might increase upper airway resistance per se, the interrupter resistance of the respiratory system (Rint,rs) was computed with and without NEP by using the flow interruption technique in 12 awake healthy subjects, 6 nonsnorers (NS), and 6 nonapneic snorers (S). Expiratory flow (V) and Rint,rs were measured under control conditions with V increased voluntarily and during random application of brief (0.2-s) NEP pulses from -1 to -7 cmH(2)O, in both the seated and supine position. In NS, Rint,rs with spontaneous increase in V and with NEP was similar [3.10 +/- 0.19 and 3.30 +/- 0.18 cmH(2)O x l(-1) x s at spontaneous V of 1.0 +/- 0.01 l/s and at V of 1.1 +/- 0.07 l/s with NEP (-5 cmH(2)O), respectively]. In S, a marked increase in Rint,rs was found at all levels of NEP (P < 0.05). Rint,rs was 3.50 +/- 0.44 and 8.97 +/- 3.16 cmH(2)O x l(-1) x s at spontaneous V of 0.81 +/- 0.02 l/s and at V of 0.80 +/- 0.17 l/s with NEP (-5 cmH(2)O), respectively (P < 0.05). With NEP, Rint,rs was markedly higher in S than in NS both seated (F = 8.77; P < 0.01) and supine (F = 9.43; P < 0.01). In S, V increased much less with NEP than in NS and was sometimes lower than without NEP, especially in the supine position. This study indicates that during wakefulness nonapneic S have more collapsible upper airways than do NS, as reflected by the marked increase in Rint,rs with NEP. The latter leads occasionally to an actual decrease in V such as to invalidate the NEP method for detection of intrathoracic expiratory flow limitation.     

Upstream pressure for systemic to pulmonary flow from bronchial circulation in dogs

Systemic to pulmonary flow from bronchial circulation, important in perfusing potentially ischemic regions distal to pulmonary vascular obstructions, depends on driving pressure between an upstream site in intrathoracic systemic arterial network and pulmonary vascular bed. The reported increase of pulmonary infarctions in heart failure may be due to a reduction of this driving pressure. We measured upstream element for driving pressure for systemic to pulmonary flow from bronchial circulation by raising pulmonary venous pressure (Ppv) until the systemic to pulmonary flow from bronchial circulation ceased. We assumed that this was the same as upstream pressure when there was flow. Systemic to pulmonary flow from bronchial circulation was measured in left lower lobes (LLL) of 21 anesthetized open-chest dogs from volume of blood that overflowed from pump-perfused (90-110 ml/min) pulmonary vascular circuit of LLL and was corrected by any changes of LLL fluid volume (wt). Systemic to pulmonary flow from bronchial circulation upstream pressure was linearly related to systemic arterial pressure (slope = 0.24, R = 0.845). Increasing Ppv caused a progressive reduction of systemic to pulmonary flow from bronchial circulation, which stopped when Ppv was 44 +/- 6 cmH2O and pulmonary arterial pressure was 46 +/- 7 cmH2O. A further increase in Ppv reversed systemic to pulmonary flow from bronchial circulation with blood flowing back into the dog. When net systemic to pulmonary flow from bronchial circulation by the overflow and weight change technique was zero a small bidirectional flow (3.7 +/- 2.9 ml.min-1 X 100 g dry lobe wt-1) was detected by dispersion of tagged red blood cells that had been injected.(ABSTRACT TRUNCATED AT 250 WORDS)     

O2-mediated oxidation of hemopexin-heme(II)-NO

Hemopexin (HPX), serving as scavenger and transporter of toxic plasma heme, has been postulated to play a key role in the homeostasis of NO. Here, kinetics of HPX-heme(II) nitrosylation and O2-mediated oxidation of HPX-heme(II)-NO are reported. NO reacts reversibly with HPX-heme(II) yielding HPX-heme(II)-NO, according to the minimum reaction scheme: HPX-heme(II)+NO kon<-->koff HPX-heme(II)-NO values of kon, koff, and K (=kon/koff) are (6.3+/-0.3)x10(3)M-1s-1, (9.1+/-0.4)x10(-4)s-1, and (6.9+/-0.6)x10(6)M-1, respectively, at pH 7.0 and 10.0 degrees C. O2 reacts with HPX-heme(II)-NO yielding HPX-heme(III) and NO3-, by means of the ferric heme-bound peroxynitrite intermediate (HPX-heme(III)-N(O)OO), according to the minimum reaction scheme: HPX-heme(II)-NO+O2 hon<--> HPX-heme(III)-N(O)OO l-->HPX-heme(III)+NO3- the backward reaction rate is negligible. Values of hon and l are (2.4+/-0.3)x10(1)M-1s-1 and (1.4+/-0.2)x10(-3)s-1, respectively, at pH 7.0 and 10.0 degrees C. The decay of HPX-heme(III)-N(O)OO (i.e., l) is rate limiting. The HPX-heme(III)-N(O)OO intermediate has been characterized by optical absorption spectroscopy in the Soret region (lambdamax=409 nm and epsilon409=1.51x10(5)M-1cm-1). These results, representing the first kinetic evidence for HPX-heme(II) nitrosylation and O2-mediated oxidation of HPX-heme(II)-NO, might be predictive of transient (pseudo-enzymatic) function(s) of heme carriers.     

O2 cost of inspiratory and expiratory resistive breathing in humans

In six normal male subjects we compared the O2 cost of resistive breathing (VO2 resp) between equivalent external inspiratory (IRL) and expiratory loads (ERL) studied separately. Each subject performed four pairs of runs matched for tidal volume, breathing frequency, flow rates, lung volume, pressure-time product, and work rate. Basal O2 uptake, measured before and after pairs of loaded runs, was subtracted from that measured during resistive breathing to obtain VO2 resp. For an equivalent load, the VO2 resp during ERL (184 +/- 17 ml O2/min) was nearly twice that obtained during IRL (97 +/- 9 ml O2/min). This twofold difference in efficiency between inspiratory and expiratory resistive breathing may reflect the relatively lower mechanical advantage of the expiratory muscles in overcoming respiratory loads. Variable recruitment of expiratory muscles may explain the large variation of results obtained in studies of respiratory muscle efficiency in normal subjects.     

Site of phrenic nerve stimulation-induced upper airway collapse: influence of expiratory time.

Electrical phrenic nerve stimulation (EPNS) applied at end expiration during exclusive nasal breathing can be used to characterize upper airway (UA) dynamics during wakefulness by dissociating phasic activation of UA and respiratory muscles. The UA level responsible for the EPNS-induced increase in UA resistance is unknown. The influence of the twitch expiratory timing (200 ms and 2 s) on UA resistance was studied in nine normal awake subjects by looking at instantaneous flow, esophageal and pharyngeal pressures, and genioglossal electromyogram (EMG) activity during EPNS at baseline and at -10 cmH(2)O. The majority of twitches had a flow-limited pattern. Twitches realized at 200 ms and 2 s did not differ in their maximum inspiratory flows, but esophageal pressure measured at maximum inspiratory flow was significantly less negative with late twitches (-6.6 +/- 2.7 and -5.0 +/- 3.0 cmH(2)O respectively, P = 0.04). Pharyngeal resistance was higher when twitches were realized at 2 s than at 200 ms (6.4 +/- 2.4 and 2.7 +/- 1.1 cmH(2)O x l(-1). s, respectively). EMG activity significant rose at peak esophageal pressure with a greater increase for late twitches. We conclude that twitch-induced UA collapse predominantly occurs at the pharyngeal level and that UA stability assessed by EPNS depends on the expiratory time at which twitches are performed.     

Excitatory lung reflex may stress inspiratory muscle by suppressing expiratory muscle activity.

Recently, a vagally mediated excitatory lung reflex (ELR) causing neural hyperpnea and tachypnea was identified. Because ventilation is regulated through both inspiratory and expiratory processes, we investigated the effects of the ELR on these two processes simultaneously. In anesthetized, open-chest, and artificially ventilated rabbits, we recorded phrenic nerve activity and abdominal muscle activity to assess the breathing pattern when the ELR was evoked by directly injecting hypertonic saline (8.1%, 0.1 ml) into lung parenchyma. Activation of the ELR stimulated inspiratory activity, which was exhibited by increasing amplitude, burst rate, and duty cycle of the phrenic activity (by 22 +/- 4, 33 +/- 9, and 57 +/- 11%, respectively; n = 13; P < 0.001), but suppressed expiratory muscle activity. The expiratory muscle became silent in most cases. On average, the amplitude of expiratory muscle activity decreased by 88 +/- 5% (P < 0.002). The suppression reached the peak at 6.9 +/- 1 s and lasted for 200 s (median). Injection of H(2)O(2) into the lung parenchyma produced similar responses. By suppressing expiration, the ELR produces a shift in the workload from expiratory muscle to inspiratory muscle. Therefore, we conclude that the ELR may contribute to inspiratory muscle fatigue, not only by directly increasing the inspiratory activity but also by suppressing expiratory activity.     

Parameters controlling the kinetics of ferric and ferrous hemeproteins reduction by hydrated electrons

To clarify the processes of hemeproteins reduction, three classes of these proteins (ferric, ferrous and desFe) were reduced by hydrated electrons generated by pulse radiolysis. Spectral and kinetic investigations were made on alpha hemoglobin chain and myoglobin. Human alpha chain has been chosen to avoid all ferric contaminations and horse ferric myoglobin to eliminate all ferrous protein fractions. We have successively studied the influences of: the iron presence, its oxidation state (II and III), the protein charge and the iron-ligand nature (H2O, OH-, N3- and CN-). For alpha human hemoglobin chain without metallic ion or with ferrous iron, the reduction rates are the same: 1.1 +/- 0.2.10(10) M-1.s-1. In the case of horse ferric myoglobin, the reduction rates depend principally on the protein charge (from pH 6.3 to pH 9.5, the reduction rate of Mb(FeIII)N3- decreases from 2.5 +/- 0.5.10(10) M-1.s-1 to 1.2 +/- 0.2.10(10) M-1.s-1) and are also modulated by the equilibrium constant of the hemeprotein-ligand association (1.2 +/- 0.2.10(10) M-1.s-1 for Mb(FeIII)N3- and 0.8 +/- 0.2.10(10) M-1.s-1 for Mb(FeIII)CN-, at pH 9.8).