Warner, David O.

To determine the relative contribution of rib cage and abdominal muscles to expiratory muscle activity during quiet breathing, we used lumbar epidural anesthesia in six pentobarbital sodium-anesthetized dogs lying supine to paralyze the abdominal muscles while leaving rib cage muscle motor function substantially intact. A high-speed X-ray scanner (Dynamic Spatial Reconstructor) provided three-dimensional images of the thorax. The contribution of expiratory muscle activity to tidal breathing was assessed by a comparison of chest wall configuration during relaxed apnea with that at end expiration. We found that expiratory muscle activity was responsible for approximately half of the changes in thoracic volume during inspiration. Paralysis of the abdominal muscles had little effect on the pattern of breathing, including the contribution of expiratory muscle activity to tidal breathing, in most dogs. We conclude that, although there is consistent phasic expiratory electrical activity in both the rib cage and the abdominal muscles of pentobarbital-anesthetized dogs lying supine, the muscles of the rib cage are mechanically the most important expiratory muscles during quiet breathing.

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.

We have previously demonstrated appreciable inhomogeneity of alveolar pressures measured by a capsule technique in excised canine lobes deflated at submaximal flows (J. Appl. Physiol. 65: 1757-1765, 1988). We further analyzed the results of these experiments by estimating alveolar volumes (VA) and regional flows from regional transpulmonary pressures, assuming that regional pressure-volume relationships were homogeneous. Deflation at submaximal flows of lungs suspended in air caused significant flow-dependent inhomogeneity of VA that increased as lung volume decreased. Immersion of lungs in stable foams that simulated the gradient of pleural pressure modified the pattern of emptying, but not always to a gravity-dependent sequence. Limitation of regional expiratory flow was often asynchronous during both air suspension and foam immersion. There was no evidence of a common regional flow-volume curve. Submaximal deflation is a complex heterogeneous process, with the interregional pattern of emptying determined by the interaction of factors that are both intrinsic and extrinsic to the lungs.

Factors both intrinsic and extrinsic to the lung may cause inhomogeneity of alveolar pressures during deflation. Wilson et al. (J. Appl. Physiol. 59: 1924-1928, 1985) predicted that any such inhomogeneity would be limited by interdependence of regional expiratory flows. To test this hypothesis and to explore how the pleural pressure gradient might affect inhomogeneity of alveolar pressures, we deflated at submaximal flows excised canine lobes that first were suspended in air and then were immersed in foams that simulated the vertical gradient of pleural pressure. Interregional inhomogeneity of regional transpulmonary pressures was measured with use of an alveolar capsule technique. Flow-dependent inhomogeneity of alveolar pressures was present, with differences in alveolar pressure quickly relaxing to a constant limiting value at each flow. Foam immersion increased inhomogeneity at a given flow. We conclude that factors intrinsic to the lung cause significant inhomogeneity of alveolar pressures at submaximal expiratory flows and that this inhomogeneity is enhanced by the extrinsic gradient of pleural pressure. These observations are consistent with the interdependence of flow proposed by Wilson et al.

The objective of this investigation was to determine the minimum transpulmonary pressure (PL) at which the forces of interdependence between the airways and the lung parenchyma can prevent airway closure in response to maximal stimulation of the airways in excised canine lobes. We first present an analysis of the relationship between PL and the transmural pressure (Ptm) that airway smooth muscle must generate to close the airways. This analysis predicts that airway closure can occur at PL less than or equal to 10 cmH2O with maximal airway stimulation. We tested this prediction in eight excised canine lobes by nebulizing 50% methacholine into the airways while the lobe was held at constant PL values ranging from 25 to 5 cmH2O. Airway closure was assessed by comparing changes in alveolar pressure (measured by an alveolar capsule technique) and pressure at the airway opening during low-amplitude oscillations in lobar volume. Airway closure occurred in two of the eight lobes at PL = 10 cmH2O; in an additional five it occurred at PL = 7.5 cmH2O. We conclude that the forces of parenchymal interdependence per se are not sufficient to prevent airway closure at PL less than or equal to 7.5 cmH2O in excised canine lobes.

This study tested the effects of sympathetically mediated changes in blood flow to active muscles on muscle O2 uptake (VO2) in humans. Four minutes of graded (15-80% of maximum voluntary contraction, MVC) rhythmic handgrip exercise were performed. Forearm blood flow (FBF) (plethysmography) and deep vein O2 saturation were measured each minute. Forearm O2 uptake was calculated using the Fick principle. In protocol 1, exercise was performed while supine and again while upright to augment sympathetic outflow to the active muscles. Standing reduced FBF at rest from 3.6 to 2.2 ml.100 ml-1.min-1 (P < 0.05). During light exercise (15-40% MVC) FBF was unaffected by body position. Standing reduced FBF (P < 0.05) from 36.0 to 25.2 ml.100 ml-1.min-1 and forearm VO2 from 38.2 to 28.1 ml.kg-1.min-1 during the final work load. In protocol 2, exercise was performed while supine before and after local anesthetic block of the sympathetic nerves to the forearm. Sympathetic block increased FBF at rest from 3.1 to 8.9 ml.100 ml-1.min-1 (P < 0.05), and FBF was higher during all work loads At 70-80% of MVC sympathetic block increased FBF from 35.4 to 50.7 ml.100 ml-1.min-1 (P < 0.05), and forearm VO2 from 45.5 to 54.2 ml.kg-1.min-1 (P < 0.05). These results suggest that in humans sympathetic nerves modulate blood flow to active muscles during light and heavy rhythmic exercise and that this restraint of flow can limit O2 uptake in muscles performing heavy rhythmic exercise.

We performed the quasi-static single-breath oxygen test (SBO2) in 16 excised canine lower lung lobes while the lobes were first suspended in air and then later immersed in stable foams that provided a vertical transpulmonary pressure gradient. In lobes suspended in air, an approximately linear alveolar plateau (AP) was obtained. The AP during foam immersion was markedly curvilinear, with phase IV seen at end expiration. The observed AP during foam immersion could be predicted by a mathematical model that assumed a homogeneous transpulmonary pressure-regional volume relationship equal to the overall pressure-volume (PV) relationship measured with the lobe suspended in air. The accuracy of this model was further confirmed by measuring the washout of nitrogen injected into different lung regions through alveolar capsules. We also used the model to examine the relationship between the onset of dependent airway closure and two of its proposed indicators: the onset of phase IV and the inflection point of the overall PV relationship. In most lobes, the lung volume at the onset of phase IV was less than the modeled lung volume at dependent airway closure. The lung volume at the inflection point was always less than the modeled lung volume at dependent airway closure. We show that the overall PV relationship measured in lobes suspended in air provides an accurate estimate of regional PV relationships during foam immersion.

We measured the volume change of the thoracic cavity (delta Vth) and the volumes displaced by the diaphragm (delta Vdi) and rib cage (delta Vrc) in six pentobarbital-anesthetized dogs lying supine. A high-speed X-ray scanner (dynamic spatial reconstructor) provided three-dimensional images of the thorax during spontaneous breathing and during mechanical ventilation with paralysis. Tidal volume (VT) was measured by integrating gas flow. Changes in thoracic liquid volume (delta Vliq, presumably caused by changes in thoracic blood volume) were calculated as delta Vth - VT. Absolute volume displaced by the rib cage was not significantly different during the two modes of ventilation. During spontaneous breathing, thoracic blood volume increased during inspiration; delta Vliq was 12.3 +/- 4.1% of delta Vth. During mechanical ventilation, delta Vliq was nearly zero. Configuration of the relaxed chest wall was similar during muscular relaxation induced by either pharmacological paralysis or hyperventilation. Expiratory muscle activity produced 50 +/- 11% of the delta Vth during spontaneous breathing. We conclude that at constant VT the volume displaced by the rib cage is remarkably similar during the transition from spontaneous breathing to mechanical ventilation, while both diaphragmatic volume displacement and changes in intrathoracic blood volume decrease by a similar amount.

To quantify the inhomogeneity of alveolar pressures (PA) during cyclic changes in lung volume similar to those present during spontaneous breathing, inhomogeneity of PA was measured with an alveolar capsule technique in six excised canine lungs. The lungs were ventilated by a quasi-sinusoidal pump with a constant end-expiratory lung volume and tidal volumes of 10, 20, and 40% of vital capacity at breathing frequencies ranging from 5 to 45 breaths/min. Inhomogeneity of PA was quantified as the sample standard deviation of pressures measured in three capsules. A component of inhomogeneity in phase with flow and a smaller component out of phase with flow were present. The in-phase component increased approximately linearly with flow. The ratio of inhomogeneity to flow was smaller at large tidal volumes and, at the two higher tidal volumes studied, the ratio was greater during inspiration than during expiration. If these data are interpreted in terms of a simple circuit model, this degree of inhomogeneity implies an approximately twofold variation in regional time constants. Despite these considerable differences in time constants, the absolute amount of inhomogeneity as defined by the sample standard deviation of the three PA's was small (maximum 0.57 +/- 0.32 cmH2O at the highest breathing frequency and tidal volume) because airway resistance in the canine lung was small.

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.