Rib cage versus abdominal displacement in rabbits during forced oscillations to 30 Hz

We measured relative displacement of the rib cage (RC) and abdomen (ABD) in 12 anesthetized rabbits during forced oscillations. Sinusoidal volume changes were delivered through a tracheostomy at frequencies from 0.5 to 30 Hz and measured by body plethysmography. Displacements of the RC and ABD were measured by inductive plethysmography. During oscillation at fixed tidal volume (VT = 1.3 ml/kg) the ratio ABD/RC, normalized to unity at 0.5 Hz, was 0.88 +/- 0.06 at 2 Hz and increased to 1.28 +/- 0.13 at 6 Hz (P less than 0.01). As frequency increased further ABD/RC fell sharply but between 20 and 30 Hz reached a plateau of 0.17 +/- 0.02 (P less than 0.001). Displacements of RC and ABD were nearly synchronous from 0.5 to 2 Hz, but as frequency increased ABD lagged RC progressively, reaching a phase difference of 90 degrees between 6 and 8 Hz and 180 degrees between 16 and 20 Hz. In six additional rabbits we measured chest wall displacements while varying VT from 0.5 to 3.7 ml/kg. ABD/RC was independent of VT at low frequencies (less than or equal to 6 Hz) but fell sharply with increasing VT at the higher frequencies. We interpreted these findings using a chest wall model having an RC compartment whose displacements are governed primarily by a nonlinear compliance, in parallel with an ABD compartment whose displacements are governed by a series resistance, inertance, and in addition a nonlinear compliance. The experimental findings are in large measure accounted for by such a model if the degree of nonlinearity of ABD and RC compliances are comparable.(ABSTRACT TRUNCATED AT 250 WORDS)     

Preferential axial flow during high-frequency oscillations: effects of gas density

Allen et al. (J. Clin. Invest. 76: 620-629, 1985) reported that regional phasic lung distension during high-frequency oscillations (HFO) is substantially and systemically heterogeneous when both frequency (f) and tidal volume (VT) are large. They hypothesized that this phenomenon was attributable to central airway geometry and preferential axial flow induced therein by the momentum flux of the inspiratory gas stream. According to that hypothesis, the observed distribution of phasic lung distension would depend on the ratio VT/VD* (where VD* is an index of anatomic dead space), independent of gas density (rho), when f is scaled in proportion to lung resonant frequency, fo. To test this hypothesis, we used the methods of Allen et al. (ibid.) to study six excised dog lungs during HFO (f = 2-32 Hz; VT = 5-80 ml) using gases of different densities. Alveolar pressure excursions (PA) were measured as rho spanned a 12-fold range using He, air, and SF6. The apex-to-base and right-to-left ratios of PA were used as indexes of regional heterogeneity of phasic lung distension. For each gas at low f, distension of the lung base was favored slightly independent of VT, but at higher f distension of the lung apex was favored when VT was small, whereas distension of the lung base was favored when VT was large. In addition, we observed substantial right-to-left differences in apical lobes during oscillation at high f not seen before.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of continuous negative airway pressure on lung volume and respiratory resistance.

This study was designed to determine the responses of lung volume and respiratory resistance (Rrs) to decreasing levels of continuous negative airway pressure (CNAP). Twenty normal subjects were studied in the basal state and under CNAP levels of -5, -10, and -15 hPa. Rrs was measured by the forced oscillation technique (4-32 Hz). End-expiratory lung volume (EELV) and tidal volume (VT) were measured by whole body plethysmography. Rrs was extrapolated to 0 Hz (R(0)) and estimated at 16 Hz (R(16)) by linear regression analysis of Rrs vs. frequency. Specific Rrs, SR(0) and SR(16), were then calculated as R(0) (EELV + VT/2) and R(16) (EELV + VT/2), respectively. EELV significantly decreased, whereas R(0), R(16), SR(0), and SR(16) significantly increased, as the CNAP level decreased (P < 0.0001 for all). At the lowest CNAP level, R(0) and R(16) reached 198 +/- 13 and 175 +/- 9% of their respective basal values. The CNAP-induced increase in R(0) was significantly higher than that in R(16) (P < 0.004). Our results demonstrate that the CNAP-induced increase in Rrs does not result from a direct lung volume effect only and strongly suggest the involvement of other factors affecting both intrathoracic and extrathoracic airway caliber.     

Diaphragmatic displacement measured by fluoroscopy and derived by Respitrace

In eight healthy volunteers we simultaneously measured the axial diaphragmatic motion by fluoroscopy and the cross-sectional area changes of the rib cage (RC) and abdomen (ABD) by Respitrace (RIP) during semistatic vital capacities (VC). We found that, if the fluoroscopic axial displacement of the posterior part of the diaphragm between residual volume (RV) and total lung capacity (TLC) is considered equal to 100%, the movement of the middle part is 90%, whereas that of the anterior part is only approximately 60%; the ratio of the axial displacements to mouth volume, furthermore, decreases at high lung volumes, especially for the anterior part. The RIP signal is nearly linearly related to mouth volume, but the contribution of the RC (delta RC) progressively increases (and is approximately 80% RIP at TLC), whereas the volume contribution of the ABD (delta ABD) levels off (to 20% RIP at TLC). The diaphragmatic volume displacement calculated from the theoretical analysis described by Mead and Loring also levels off at high volumes similarly as the ABD but is approximately 50% RIP at TLC. Finally, the axial movements of the three parts of the diaphragm are linearly related to the RC and ABD cross-sectional-area changes (r 0.91-0.97) and are even significantly better correlated with the "calculated" diaphragmatic volume displacement.     

Lung epithelial permeability to aerosolized solutes: relation to position

The lung epithelial permeability to inhaled solutes is primarily attributed to the degree of distension of the interepithelial junctions and thus of the alveolar volume. To assess this hypothesis, a submicronic aerosol of technetium-99m-labeled diethylenetriamine pentaacetate (99mTc-DTPA) was inhaled by eight normal subjects in left lateral decubitus (LLD). The regional lung clearance of 99mTc-DTPA was measured in LLD, then in right lateral decubitus (RLD) to reverse the relative distension of the alveoli. Although in LLD the deposition of the aerosol is the greatest in the gravity-dependent regions of the left lung, their 99mTc-DTPA clearances are significantly lower than those of the nondependent regions of the right lung (0.7 +/- 0.3 vs. 2 +/- 0.8%/min, P less than 0.001). In RLD, these regions placed in opposite positions significantly reversed their clearances (1.6 +/- 0.8 vs. 0.6 +/- 0.2%/min, P less than 0.001). Results indicate in lateral decubitus a gravity gradient of 99mTc-DTPA clearances independent of the aerosol deposition. This gradient of epithelial permeability to solutes appears to be influenced by the gradient of alveolar volume.     

Effect of lung volume on ventilation distribution

To examine the effect of preinspiratory lung volume (PILV) on ventilation distribution, we performed multiple-breath N2 washouts (MBNW) in seven normal subjects breathing 1-liter tidal volumes over a wide range of PILV above closing capacity. We measured the following two independent indexes of ventilation distribution from the MBNW: 1) the normalized phase III slope of the final breaths of the washout (Snf) and 2) the alveolar mixing efficiency during that portion of the washout where 80-90% of the lung N2 had been cleared. Three of the subjects also performed single-breath N2 washouts (SBNW) by inspiring 1-liter breaths and expiring to residual volume at PILV = functional residual capacity (FRC), FRC + 1.0, and FRC - 0.5, respectively. From the SBNW we measured the phase III slope over the expired volume ranges of 0.75-1.0, 1.0-1.6, and 1.6-2.2 liters (S0.75, S1.0, and S1.6, respectively). Between a PILV of 0.92 +/- 0.09 (SE) liter above FRC and a PILV of 1.17 +/- 0.43 liter below FRC, Snf decreased by 61% (P less than 0.001) and alveolar mixing efficiency increased from 80 to 85% (P = 0.05). In addition, Snf and alveolar mixing efficiency were negatively correlated (r = 0.74). In contrast, over a similar volume range, S1.0 and S1.6 were greater at lower PILV. We conclude that, during tidal breathing in normal subjects, ventilation distribution becomes progressively more inhomogeneous at higher lung volumes over a range of volumes above closing capacity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Frequency and amplitude effects during high-frequency vibration ventilation in dogs

High-frequency external body vibration, combined with constant gas flow at the tracheal carina, was previously shown to be an effective method of ventilation in normal dogs. The effects of frequency (f) and amplitude of the vibration were investigated in the present study. Eleven anesthetized and paralyzed dogs were placed on a vibrating table (4-32 Hz). O2 was delivered near the tracheal carina at 0.51.kg-1.min-1, while mean airway pressure was kept at 2.4 +/- 0.9 cmH2O. Table vertical displacement (D) and acceleration (a), esophageal (Pes), and tracheal (Ptr) peak-to-peak pressures, and tidal volume (VT) were measured as estimates of the input amplitude applied to the animal. Steady-state arterial PCO2 (PaCO2) and arterial PO2 (PaO2) values were used to monitor overall gas exchange. Typically, eucapnia was achieved with f greater than 16 Hz, D = 1 mm, a = 1 G, Pes = Ptr = 4 +/- 2 cmH2O, and VT less than 2 ml. Inverse exponential relationships were found between PaCO2 and f, a, Pes, and Ptr (exponents: -0.69, -0.38, -0.48, and -0.54, respectively); PaCO2 decreased linearly with increased displacement or VT at a fixed frequency (17 +/- 1 Hz). PaO2 was independent of both f and D (393 +/- 78 Torr, mean +/- SD). These data demonstrate the very small VT, Ptr, and Pes associated with vibration ventilation. It is clear, however, that mechanisms other then those described for conventional ventilation and high-frequency ventilation must be evoked to explain our data. One such possible mechanism is forcing of flow oscillation between lung regions (i.e., forced pendelluft).     

Gas transport during high-frequency ventilation

During high-frequency small-volume ventilation (HFV), the transport rate of gas from the mouth to a lung region is a function of two conductances (conductance is the transfer rate of a gas divided by its partial pressure difference): regional longitudinal gas conductance along the airways (Grlongi) and gas conductance between lung regions (Ginter). Grlongi per unit regional lung (gas) volume [Grlongi/(Vr beta g)] was determined during HFV in 11 anesthetized paralyzed dogs lying supine. The distribution of Grlongi/(Vr beta g) was nearly uniform during HFV when stroke volumes were less than approximately two-thirds of the Fowler dead-space volume. By contrast, the distribution of Grlongi/(Vr beta g) was nonuniform when the stroke volume exceeded approximately two-thirds of the Fowler dead-space volume and the oscillation frequency was 5 Hz. Gas conductance along the airways per unit lung gas volume [average Glongi/(V beta g)], for the entire lung, increased with stroke volume at all frequencies, but for a given product of oscillation frequency and stroke volume, the average Glongi/(V beta g) was greater when stroke volume was large and oscillation frequency was low. The average Glongi/(V beta g) increased with frequency up to a maximal value; the frequency at which the maximum occurred depended on the kinematic viscosity of the inspired gas mixture.     

Partitioning of pulmonary resistance in dogs: effect of tidal volume and frequency

To determine the sensitivity of pulmonary resistance (RL) to changes in breathing frequency and tidal volume, we measured RL in intact anesthetized dogs over a range of breathing frequencies and tidal volumes centering around those encountered during quiet breathing. To investigate mechanisms responsible for changes in RL, the relative contribution of airway resistance (Raw) and tissue resistance (Rti) to RL at similar breathing frequencies and tidal volumes was studied in six excised, exsanguinated canine left lungs. Lung volume was sinusoidally varied, with tidal volumes of 10, 20, and 40% of vital capacity. Pressures were measured at three alveolar sites (PA) with alveolar capsules and at the airway opening (Pao). Measurements were made during oscillation at five frequencies between 5 and 45 min-1 at each tidal volume. Resistances were calculated by assuming a linear equation of motion and submitting lung volume, flow, Pao, and PA to a multiple linear regression. RL decreased with increasing frequency and decreased with increasing tidal volume in both isolated and intact lungs. In isolated lungs, Rti decreased with increasing frequency but was independent of tidal volume. Raw was independent of frequency but decreased with tidal volume. The contribution of Rti to RL ranged from 93 +/- 4% (SD) with low frequency and large tidal volume to 41 +/- 24% at high frequency and small tidal volume. We conclude that the RL is highly dependent on breathing frequency and less dependent on tidal volume during conditions similar to quiet breathing and that these findings are explained by changes in the relative contributions of Raw and Rti to RL.     

Effect of intestinal afferent stimulation on pattern of respiratory muscle activation

The purpose of the present study was to examine the reflex effects of mechanical stimulation of intestinal visceral afferents on the pattern of respiratory muscle activation. In 14 dogs anesthetized with pentobarbital sodium, electromyographic activity of the costal and crural diaphragm, parasternal intercostal, and upper airway respiratory muscles was measured during distension of the small intestine. Rib cage and abdominal motion and tidal volume were also recorded. Distension produced an immediate apnea (11.16 +/- 0.80 s). During the first postapneic breath, costal (43 +/- 7% control) and crural (64 +/- 6% control) activity were reduced (P less than 0.001). In contrast, intercostal (137 +/- 11%) and upper airway muscle activity, including alae nasi (157 +/- 16%), genioglossus (170 +/- 15%), and posterior cricoarytenoid muscles (142 +/- 7%) all increased (P less than 0.005). There was greater outward rib cage motion although the abdomen moved paradoxically inward during inspiration, resulting in a reduction in tidal volume (82 +/- 6% control) (P less than 0.005). Postvagotomy distension produced a similar apnea and subsequent reduction in costal and crural activity. However, enhancement of intercostal and upper airway muscle activation was abolished and there was a greater fall in tidal volume (65 +/- 14%). In conclusion, mechanical stimulation of intestinal afferents affects the various inspiratory muscles differently; nonvagal afferents produce an initial apnea and subsequent depression of diaphragm activity whereas vagal pathways mediate selective enhancement of intercostal and upper airway muscle activation.     

Ventilation by external high-frequency oscillation in cats

Eight anesthetized tracheostomized cats were placed in an 8.2-liter airtight chamber with the trachea connected to the exterior. Thirty-two combinations of high-frequency oscillations (HFO) (0.5-30 Hz; 25-100 ml) were delivered for 10 min each in random order into the chamber. Arterial blood gas tensions during oscillation were compared with control measurements made after 10 min of spontaneous breathing without oscillation when the mean arterial PCO2 (PaCO2) was 30.1 Torr. Ventilation due to spontaneous breathing (Vs) and oscillation (Vo) were derived from the chamber pressure trace and a pneumotachograph, respectively. As the oscillation frequency increased, oscillated tidal volume (Vo) decreased from a mean of 39 (0.5 Hz) to 3.3 ml (30 Hz) when 100 ml was delivered to the chamber. From 6-25 Hz, apnea occurred with Vo less than estimated respiratory dead space (VD); the minimum effective Vo/VD ratio was 0.37 +/- 0.05. Although Vo was maximal at 10 Hz at each oscillation volume, the lowest PaCO2 occurred at 2-6 Hz, and arterial PO2 rose as expected during hypocapnia. Above 10 Hz, PaCO2 was determined by Vo and was independent of frequency, whereas at lower frequencies, PaCO2 was related to Vo; below 6 Hz, PaCO2 varied inversely with the calculated alveolar ventilation. As oscillations became more effective, both PaCO2 and Vs fell progressively and were highly correlated; apnea occurred when PaCO2 was reduced by a mean of 4.5 Torr. Mean chamber pressure remained near zero up to 15 Hz, indicating functional residual capacity did not change. We conclude that externally applied HFO can readily maintain gas exchange in vivo, with Vo less than VD at frequencies over 2 Hz.     

Lung pressures and gas transport during high-frequency airway and chest wall oscillation

The major goal of this study was to compare gas exchange, tidal volume (VT), and dynamic lung pressures resulting from high-frequency airway oscillation (HFAO) with the corresponding effects in high-frequency chest wall oscillation (HFCWO). Eight anesthetized paralyzed dogs were maintained eucapnic with HFAO and HFCWO at frequencies ranging from 1 to 16 Hz in the former and 0.5 to 8 Hz in the latter. Tracheal (delta Ptr) and esophageal (delta Pes) pressure swings, VT, and arterial blood gases were measured in addition to respiratory impedance and static pressure-volume curves. Mean positive pressure (25-30 cmH2O) in the chest cuff associated with HFCWO generation decreased lung volume by approximately 200 ml and increased pulmonary impedance significantly. Aside from this decrease in functional residual capacity (FRC), no change in lung volume occurred as a result of dynamic factors during the course of HFCWO application. With HFAO, a small degree of hyperinflation occurred only at 16 Hz. Arterial PO2 decreased by 5 Torr on average during HFCWO. VT decreased with increasing frequency in both cases, but VT during HFCWO was smaller over the range of frequencies compared with HFAO. delta Pes and delta Ptr between 1 and 8 Hz were lower than the corresponding pressure swings obtained with conventional mechanical ventilation (CMV) applied at 0.25 Hz. delta Pes was minimized at 1 Hz during HFCWO; however, delta Ptr decreased continuously with decreasing frequency and, below 2 Hz, became progressively smaller than the corresponding values obtained with HFAO and CMV.     

Flow limitation, cough, and patterns of aerosol deposition in humans

We studied deposition of radioactive monodisperse 1.5-micron aerosol in humans following inhalation during quiet breathing. Two groups were studied: normal, defined by tidal loops below the maximum expiratory flow-volume (MEFV) envelope [forced expiratory volume at 1 s at percent of forced vital capacity (FEV1%) 62-78]; and flow-limited, with tidal loops superimposed on MEFV relationship (FEV1% 21-57) and flow-limiting segments (FLS) known to exist in central airways. During simultaneous imaging with a gamma camera, fraction of inhaled aerosol deposited in the lung (DF) was determined by right-angle light scattering. With regions of interest defined by an equilibrium image of 133Xe, regional deposition was normalized for area and lung thickness and expressed as a central-to-peripheral (C/P) ratio. Deposition was uniform throughout the lung in normal subjects [C/P 1.02 +/- 0.07 (SD), n = 6]. In flow-limited group, central deposition predominated (C/P 1.98 +/- 0.64, n = 6, P less than 0.05). Tidal volume and inspiratory flow, forces thought to influence deposition during inspiration, were not different between groups. Spontaneous cough occurred in five flow-limited subjects during aerosol inhalation, with further increase in central deposition when compared with quiet breathing (C/P 1.85 +/- 0.60 to 2.69 +/- 0.600, P less than 0.01). During cough, tidal volume (ml) was reduced significantly (576 +/- 151 to 364 +/- 117, P less than 0.01) with no change in inspiratory flow (l/s) (1.37 +/- 0.23 to 1.38 +/- 0.40, P = NS). DF, however, was unaffected by cough (0.34 +/- 0.13 to 0.61 +/- 0.12, P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)     

Ventilatory effectiveness of high-frequency oscillation applied to the body surface

To determine the ventilatory effectiveness of high-frequency oscillation (HFO) at different sites on the body surface, we applied HFO separately to the abdomen, the rib cage, or the whole body in eight anesthetized and paralyzed dogs. Test frequencies were 5, 7, 9, and 11 Hz with tidal volume kept constant at 2.5 ml/kg. During HFO application to the abdomen, we observed significantly higher arterial O2 partial pressure (P less than 0.05) at 5, 7, and 9 Hz and lower arterial CO2 partial pressure (P less than 0.05) at 7, 9, and 11 Hz than with rib cage or whole-body HFO. There was no significant difference in blood gases between rib cage and whole-body HFO. Thus, using blood gases as an index of ventilatory effectiveness, the present study showed that HFO applied at the abdomen was the most effective of the three kinds of body surface HFO. In comparison to rib cage or whole-body application, abdominal HFO was accompanied by substantial paradoxical movement of the diaphragm and rib cage. The associated lung distortion may result in pendelluft, which in turn may be the mechanism for increased ventilatory effectiveness with abdominal application of HFO.     

Effect of mean airway pressure on gas exchange during high-frequency oscillatory ventilation

We studied the effect of mean airway pressure (Paw) on gas exchange during high-frequency oscillatory ventilation in 14 adult rabbits before and after pulmonary saline lavage. Sinusoidal volume changes were delivered through a tracheostomy at 16 Hz, a tidal volume of 1 or 2 ml/kg, and inspired O2 fraction of 0.5. Arterial PO2 and PCO2 (PaO2, PaCO2), lung volume change, and venous admixture were measured at Paw from 5 to 25 cmH2O after either deflation from total lung capacity or inflation from relaxation volume (Vr). The rabbits were lavaged with saline until PaO2 was less than 70 Torr, and all measurements were repeated. Lung volume change was measured in a pressure plethysmograph. Raising Paw from 5 to 25 cmH2O increased lung volume by 48-50 ml above Vr in both healthy and lavaged rabbits. Before lavage, PaO2 was relatively insensitive to changes in Paw, but after lavage PaO2 increased with Paw from 42.8 +/- 7.8 to 137.3 +/- 18.3 (SE) Torr (P less than 0.001). PaCO2 was insensitive to Paw change before and after lavage. At each Paw after lavage, lung volume was larger, venous admixture smaller, and PaO2 higher after deflation from total lung capacity than after inflation from Vr. This study shows that the effect of increased Paw on PaO2 is mediated through an increase in lung volume. In saline-lavaged lungs, equal distending pressures do not necessarily imply equal lung volumes and thus do not imply equal PaO2.     

Effect of changes in lung volume on respiratory system compliance in newborn infants

Total respiratory system compliance (Crs) at volumes above the tidal volume (VT) was studied by use of the expiratory volume clamping (EVC) technique in 10 healthy sleeping unsedated newborn infants. Flow was measured with a pneumotachograph attached to a face mask and integrated to yield volume. Volume changes were confirmed by respiratory inductance plethysmography. Crs measured by EVC was compared with Crs during tidal breathing determined by the passive flow-volume (PFV) technique. Volume increases of approximately 75% VT were achieved with three to eight inspiratory efforts during expiratory occlusions. Crs above VT was consistently greater than during tidal breathing (P less than 0.0005). This increase in Crs likely reflects recruitment of lung units that are closed or atelectatic in the VT range. Within the VT range, Crs measured by PFV was compared with that obtained by the multiple-occlusion method (MO). PFV yielded greater values of Crs than MO (P less than 0.01). This may be due to braking of expiratory airflow after the release of an occlusion or nonlinearity of Crs. Thus both volume recruitment and airflow retardation may affect the measurement of Crs in unsedated newborn infants.     

Mechanical role of expiratory muscle recruitment during eupnea in supine anesthetized dogs

To assess the mechanical role of the expiratory musculature during eupnea, we recorded the electromyographic (EMG) activity of the triangularis sterni, the external oblique, and the transversus abdominis in eight supine lightly anesthetized dogs and have measured the volume generated by the phasic activation of the expiratory muscles. Activation of the expiratory muscles was invariably associated with a decrease in lung volume below the relaxed position of the respiratory system, a volume equal to 41.3 +/- 8.4 ml. This volume represented roughly 20% of tidal volume generated during spontaneous breathing. The fractional expiratory contribution to the tidal volume was unrelated to the size of the animal. Traction on the forelimbs (limb extension), however, tended to enhance the phasic expiratory activation of both the triangularis sterni and the transversus abdominis in the majority of animals. Moreover, after limb extension, the fractional contribution of tidal volume attributed to the phasic activation of the expiratory muscles increased in all but one animal. During spontaneous breathing with the forelimbs extended, roughly 25% of tidal volume was found to be due directly to phasic expiratory muscle contraction. The present observations firmly establish that in supine lightly anesthetized dogs breathing at rest the expiratory component of tidal volume represents a substantial contribution.     

Microinjection of DLH into the region of the caudal ventral respiratory column in the cat: evidence for an endogenous cough-suppressant mechanism.

The caudal ventral respiratory column (cVRC) contains premotor expiratory neurons that play an important role in cough-related expiratory activity of chest wall and abdominal muscles. Microinjection of d,l-homocysteic acid (DLH) was used to test the hypothesis that local activation of cVRC neurons can suppress the cough reflex. DLH (20-50 mM, 10-30 nl) was injected into the region of cVRC in nine anesthetized spontaneously breathing cats. Repetitive coughing was elicited by mechanical stimulation of the intrathoracic airways. Electromyograms (EMG) were recorded bilaterally from inspiratory parasternal and expiratory transversus abdominis (ABD) and unilaterally from laryngeal posterior cricoarytenoid and thyroarytenoid muscles. Unilateral microinjection of DLH (1-1.5 nmol) elicited bilateral increases in tonic and phasic respiratory ABD EMG activity, and it altered the respiratory pattern and laryngeal motor activities. However, DLH also decreased cough frequency by 51 +/- 7% compared with control (P < 0.001) and the amplitude of the contralateral (-35 +/- 3%; P < 0.001) and ipsilateral (-34 +/- 5%; P < 0.001) ABD EMGs during postinjection coughs compared with control. The cough alterations were much less pronounced after microinjection of a lower dose of DLH (0.34-0.8 nmol). No cough depression was observed after microinjections of vehicle. These results suggest that an endogenous cough suppressant neuronal network in the region of the cVRC may exist, and this network may be involved in the control of cough reflex excitability.     

Postural effects on measurements of tidal volume from body surface displacements

Tidal volume measurements based on the sum of volume displacements of the rib cage (RC) and abdomen (Ab) are limited in accuracy when changes in posture occur. To elucidate the underlying sources of error, five subjects performed spinal flexion-extension isovolume maneuvers and then performed Konno-Mead isovolume maneuvers at different lung volumes while erect, with the spine fully flexed, and at intermediate degrees of spinal flexion. RC and Ab dimensions were measured with respiratory inductance plethysmograph belts, and spinal flexion was assessed by a pair of magnetometers measuring the xiphi-Ab distance (Xi). RC and Ab volume-motion coefficients (alpha and beta, respectively) were calculated from the slope (-beta/alpha) of the Konno-Mead isovolume lines. We found that 1) spinal flexion with constant lung volume mainly increases the RC dimension, thereby displacing the Konno-Mead isovolume lines, and 2) spinal flexion decreases the -beta/alpha by decreasing beta. The error related to displacement averaged 28.4 +/- 15% of vital capacity, whereas the error related to changes in beta averaged 14 +/- 6% (SD). The systematic relationship of these errors with the degree of spinal flexion provides a mechanism whereby the addition of Xi to RC and Ab displacements significantly (P less than 0.001) improves volume estimates.     

Heterogeneous responses of human limbs to infused adrenergic agonists: a gravitational effect?

Unlike quadrupeds, the legs of humans are regularly exposed to elevated pressures relative to the arms. We hypothesized that this "dependent hypertension" would be associated with altered adrenergic responsiveness. Isoproterenol (0.75-24 ng x 100 ml limb volume-1 x min-1) and phenylephrine (0.025-0.8 microg x 100 ml limb volume-1 x min-1) were infused incrementally in the brachial and femoral arteries of 12 normal volunteers; changes in limb blood flow were quantified by using strain-gauge plethysmography. Compared with the forearm, baseline calf vascular resistance was greater (38.8 +/- 2.5 vs. 26.9 +/- 2.0 mmHg x 100 ml x min x ml-1; P < 0.001) and maximal conductance was lower (46.1 +/- 11.9 vs. 59.4 +/- 13.4 ml x ml-1 x min-1 x mmHg-1; P < 0.03). Vascular conductance did not differ between the two limbs during isoproterenol infusions, whereas decreases in vascular conductance were greater in the calf than the forearm during phenylephrine infusions (P < 0.001). With responses normalized to maximal conductance, the half-maximal response for phenylephrine was significantly less for the calf than the forearm (P < 0.001), whereas the half-maximal response for isoproterenol did not differ between limbs. We conclude that alpha1- but not beta-adrenergic-receptor responsiveness in human limbs is nonuniform. The relatively greater response to alpha1-adrenergic-receptor stimulation in the calf may represent an adaptive mechanism that limits blood pooling and capillary filtration in the legs during standing.