Dysfunction of the canine respiratory muscle pump in ascites.

Ascites, a complicating feature of many diseases of the liver and peritoneum, commonly causes dyspnea. The mechanism of this symptom, however, is uncertain. In the present study, progressively increasing ascites was induced in anesthetized dogs, and the hypothesis was initially tested that ascites increases the impedance on the diaphragm and, so, adversely affects the lung-expanding action of the muscle. Ascites produced a gradual increase in abdominal elastance and an expansion of the lower rib cage. Concomitantly, the caudal displacement of the diaphragm and the fall in airway opening pressure during isolated stimulation of the phrenic nerves decreased markedly; transdiaphragmatic pressure during phrenic stimulation also decreased. To assess the adaptation to ascites of the respiratory system overall, we subsequently measured the changes in lung volume, the arterial blood gases, and the electromyogram of the parasternal intercostal muscles during spontaneous breathing. Tidal volume and minute ventilation decreased progressively as ascites increased, leading to an increase in arterial PCO2 and parasternal intercostal inspiratory activity. It is concluded that 1) ascites, acting through an increase in abdominal elastance and an expansion of the lower rib cage, impairs the lung-expanding action of the diaphragm; 2) this impairment elicits a compensatory increase in neural drive to the inspiratory muscles, but the compensation is not sufficient to maintain ventilation; and 3) dyspnea in this setting results in part from the dissociation between increased neural drive and decreased ventilation.     

Effect of lung volume on the respiratory action of the canine pectoral muscles.

Lung volume influences the mechanical action of the primary inspiratory and expiratory muscles by affecting their precontraction length, alignment with the rib cage, and mechanical coupling to agonistic and antagonistic muscles. We have previously shown that the canine pectoral muscles exert an expiratory action on the rib cage when the forelimbs are at the torso's side and an inspiratory action when the forelimbs are held elevated. To determine the effect of lung volume on intrathoracic pressure changes produced by the canine pectoral muscles, we performed isolated bilateral supramaximal electrical stimulation of the deep pectoral and superficial pectoralis (descending and transverse heads) muscles in 15 adult supine anesthetized dogs during hyperventilation-induced apnea. Lung volume was altered by application of a negative or positive pressure (+/- 30 cmH2O) to the airway. In all animals, selective electrical stimulation of the descending, transverse, and deep pectoral muscles with the forelimbs held elevated produced negative intrathoracic pressure changes (i.e., an inspiratory action). Moreover, with the forelimbs elevated, increasing lung volume decreased both pectoral muscle fiber precontraction length and the negative intrathoracic pressure changes generated by contraction of each of these muscles. Conversely, with the forelimbs along the torso, increasing lung volume lengthened pectoral muscle precontraction length and augmented the positive intrathoracic pressure changes produced by muscle contraction (i.e., an expiratory action). These results indicate that lung volume significantly affects the length of the canine pectoral muscles and their mechanical actions on the rib cage.     

Mechanics of the parasternal intercostals during occluded breaths in dogs

The electrical activity and the respiratory changes in length of the third parasternal intercostal muscle were measured during single-breath airway occlusion in 12 anesthetized, spontaneously breathing dogs in the supine posture. During occluded breaths in the intact animal, the parasternal intercostal was electrically active and shortened while pleural pressure fell. In contrast, after section of the third intercostal nerve at the chondrocostal junction and abolition of parasternal electrical activity, the muscle always lengthened. This inspiratory muscle lengthening must be related to the fall in pleural pressure; it was, however, approximately 50% less than the amount of muscle lengthening produced, for the same fall in pleural pressure, by isolated stimulation of the phrenic nerves. These results indicate that 1) the parasternal inspiratory shortening that occurs during occluded breaths in the dog results primarily from the muscle inspiratory contraction per se, and 2) other muscles of the rib cage, however, contribute to this parasternal shortening by acting on the ribs or the sternum. The present studies also demonstrate the important fact that the parasternal inspiratory contraction in the dog is really agonistic in nature.     

Contribution of tree structures in the lung to lung elastic recoil

The direct contribution of forces in tree structures in the lung to lung recoil pressure and changes in recoil pressure induced by alterations of the forces are analyzed. The analysis distinguishes the contributions of axial and circumferential tensions in the trees and indicates that only axial tensions directly contribute to static recoil. This contribution is derived from analysis of the axial forces transmitted across a random plane transecting the lung. The change in recoil pressure induced by changes in axial tension is similarly derived. Alterations of circumferential tensions in the trees indirectly change recoil by causing nonuniform deformations of the surrounding lung parenchyma, and a continuum elasticity solution for the stress induced by the deformations is derived. Sample calculations are presented for the airway tree based on available data on airway morphometric and mechanical properties. The increase in recoil pressure accompanying increases in axial and circumferential tensions with contraction of airway smooth muscle is also analyzed. The calculations indicate that axial stresses in the airway tree out to bronchioles directly contribute only a small fraction of the static recoil pressure. However, it is found that contraction of smooth muscle in these airways can increase recoil pressure appreciably (10-20%), mainly by the deformation of the parenchyma with increases in circumferential tension in smaller airways. The results indicate that the geometric and mechanical properties of the airway tree are such that only peripheral elements of the tree can substantially affect the elastic properties of the lung. The possible contributions of vascular trees for which data on mechanical and morphometric properties are more limited are also discussed.     

Respiratory effects of the scalene and sternomastoid muscles in humans.

Previous studies have shown that in normal humans the change in airway opening pressure (DeltaPao) produced by all the parasternal and external intercostal muscles during a maximal contraction is approximately -18 cmH(2)O. This value is substantially less negative than DeltaPao values recorded during maximal static inspiratory efforts in subjects with complete diaphragmatic paralysis. In the present study, therefore, the respiratory effects of the two prominent inspiratory muscles of the neck, the sternomastoids and the scalenes, were evaluated by application of the Maxwell reciprocity theorem. Seven healthy subjects were placed in a computed tomographic scanner to determine the fractional changes in muscle length during inflation from functional residual capacity to total lung capacity and the masses of the muscles. Inflation induced greater shortening of the scalenes than the sternomastoids in every subject. The inspiratory mechanical advantage of the scalenes thus averaged (mean +/- SE) 3.4 +/- 0.4%/l, whereas that of the sternomastoids was 2.0 +/- 0.3%/l (P < 0.001). However, sternomastoid muscle mass was much larger than scalene muscle mass. As a result, DeltaPao generated by a maximal contraction of either muscle would be 3-4 cmH(2)O, which is about the same as DeltaPao generated by the parasternal intercostals in all interspaces.     

Gas exchange during separate diaphragm and intercostal muscle breathing.

In patients with diaphragm paralysis, ventilation to the basal lung zones is reduced, whereas in patients with paralysis of the rib cage muscles, ventilation to the upper lung zones in reduced. Inspiration produced by either rib cage muscle or diaphragm contraction alone, therefore, may result in mismatching of ventilation and perfusion and in gas-exchange impairment. To test this hypothesis, we assessed gas exchange in 11 anesthetized dogs during ventilation produced by either diaphragm or intercostal muscle contraction alone. Diaphragm activation was achieved by phrenic nerve stimulation. Intercostal muscle activation was accomplished by electrical stimulation by using electrodes positioned epidurally at the T(2) spinal cord level. Stimulation parameters were adjusted to provide a constant tidal volume and inspiratory flow rate. During diaphragm (D) and intercostal muscle breathing (IC), mean arterial Po(2) was 97.1 +/- 2.1 and 88.1 +/- 2.7 Torr, respectively (P < 0.01). Arterial Pco(2) was lower during D than during IC (32.6 +/- 1.4 and 36.6 +/- 1.8 Torr, respectively; P < 0.05). During IC, oxygen consumption was also higher than that during D (0.13 +/- 0.01 and 0.09 +/- 0.01 l/min, respectively; P < 0.05). The alveolar-arterial oxygen difference was 11.3 +/- 1.9 and 7.7 +/- 1.0 Torr (P < 0.01) during IC and D, respectively. These results indicate that diaphragm breathing is significantly more efficient than intercostal muscle breathing. However, despite marked differences in the pattern of inspiratory muscle contraction, the distribution of ventilation remains well matched to pulmonary perfusion resulting in preservation of normal gas exchange.     

Effect of respiratory muscle tension on lung volume.

The chest wall is modeled as a linear system for which the displacements of points on the chest wall are proportional to the forces that act on the chest wall, namely, airway opening pressure and active tension in the respiratory muscles. A standard theorem of mechanics, the Maxwell reciprocity theorem, is invoked to show that the effect of active muscle tension on lung volume, or airway pressure if the airway is closed, is proportional to the change of muscle length in the relaxation maneuver. This relation was tested experimentally. The shortening of the cranial-caudal distance between a rib pair and the sternum was measured during a relaxation maneuver. These data were used to predict the respiratory effect of forces applied to the ribs and sternum. To test this prediction, a cranial force was applied to the rib pair and a caudal force was applied to the sternum, simulating the forces applied by active tension in the parasternal intercostal muscles. The change in airway pressure, with lung volume held constant, was measured. The measured change in airway pressure agreed well with the prediction. In some dogs, nonlinear deviations from the linear prediction occurred at higher loads. The model and the theorem offer the promise that existing data on the configuration of the chest wall during the relaxation maneuver can be used to compute the mechanical advantage of the respiratory muscles.     

Inspiratory action of separate external and parasternal intercostal muscle contraction

We have previously shown that electrical stimulation of the thoracic spinal cord produces near maximal activation of the inspiratory intercostal muscles. In the present investigation, we used this technique to evaluate the relative capacity of separate external (EI) and parasternal intercostal (PA) muscle contraction to produce changes in airway pressure and inspired volume. Studies were performed in 23 anesthetized phrenicotomized dogs. Electrical stimuli were applied to the spinal cord after hyperventilation-induced apnea, before and after sequentially severing either the PA or EI muscles from the first through sixth intercostal spaces. During spinal cord stimulation (SCS), measurements were made of inspired volume (delta V) with the airway open and negative airway pressure (delta P) during tracheal occlusion. Compared with control values, sectioning of the PA muscles resulted in a 40.9% reduction in delta P and 35.7% reduction in delta V during SCS. In other animals, initial sectioning of the EI muscles produced reductions in delta P and delta V of 67.4 and 63.0, respectively, during SCS. After subsequent section of the PA muscles, SCS produced only negligible inspired volumes and changes in airway pressure. We conclude that 1) the EI and PA muscles are each capable of generating substantial changes in airway pressure and large inspired volumes and 2) the ventilatory capacity of the EI muscles exceeds that of the PA muscles.     

Effect of diaphragmatic contraction on the action of the canine parasternal intercostals.

The inspiratory intercostal muscles enhance the force generated by the diaphragm during lung expansion. However, whether the diaphragm also alters the force developed by the inspiratory intercostals is unknown. Two experiments were performed in dogs to answer the question. In the first experiment, external, cranially oriented forces were applied to the different rib pairs to assess the effect of diaphragmatic contraction on the coupling between the ribs and the lung. The fall in airway opening pressure (deltaPa(O)) produced by a given force on the ribs was invariably greater during phrenic nerve stimulation than with the diaphragm relaxed. The cranial rib displacement (Xr), however, was 40-50% smaller, thus indicating that the increase in deltaPa(O) was exclusively the result of the increase in diaphragmatic elastance. In the second experiment, the parasternal intercostal muscle in the fourth interspace was selectively activated, and the effects of diaphragmatic contraction on the deltaPa(O) and Xr caused by parasternal activation were compared with those observed during the application of external loads on the ribs. Stimulating the phrenic nerves increased the deltaPa(O) and reduced the Xr produced by the parasternal intercostal, and the magnitudes of the changes were identical to those observed during external rib loading. It is concluded, therefore, that the diaphragm has no significant synergistic or antagonistic effect on the force developed by the parasternal intercostals during breathing. This lack of effect is probably related to the constraint imposed on intercostal muscle length by the ribs and sternum.     

Heterogeneity of metabolic activity in the canine parasternal intercostals during breathing.

In the dog, the inspiratory mechanical advantage of the parasternal intercostals shows a marked spatial heterogeneity, whereas the expiratory mechanical advantage of the triangularis sterni is relatively uniform. The contribution of a particular respiratory muscle to lung volume expansion during breathing, however, depends both on the mechanical advantage of the muscle and on its neural input. To evaluate the distribution of neural input across the canine parasternal intercostals and triangularis sterni, we have examined the distribution of metabolic activity among these muscles in seven spontaneously breathing animals by measuring the uptake of the glucose tracer analog [(18)F]fluorodeoxyglucose (FDG). FDG uptake in any given parasternal intercostal was greatest in the medial bundles and decreased rapidly toward the costochondral junctions. In addition, FDG uptake in the medial parasternal bundles increased from the first to the second interspace, plateaued in the second through fifth interspaces, and then decreased progressively toward the eighth interspace. In contrast, uptake in the triangularis sterni showed no significant rostrocaudal gradient. These results overall strengthen the idea that the spatial distribution of neural input within a particular set of respiratory muscles is closely matched with the spatial distribution of mechanical advantage.     

Passive shortening of canine parasternal intercostals during breathing

We have previously demonstrated that the shortening of the canine parasternal intercostals during inspiration results primarily from the muscles' own activation (J. Appl. Physiol. 64: 1546-1553, 1988). In the present studies, we have tested the hypothesis that other inspiratory rib cage muscles may contribute to the parasternal inspiratory shortening. Eight supine, spontaneously breathing dogs were studied. Changes in length of the third or fourth right parasternal intercostal were measured during quiet breathing and during single-breath airway occlusion first with the animal intact, then after selective denervation of the muscle, and finally after bilateral phrenicotomy. Denervating the parasternal virtually eliminated the muscle shortening during quiet inspiration and caused the muscle to lengthen during occluded breaths. After phrenicotomy, however, the parasternal, while being denervated, shortened again a significant amount during both quiet inspiration and occluded breaths. These data thus confirm that a component of the parasternal inspiratory shortening is not active and results from the action of other inspiratory rib cage muscles. Additional studies in four animals demonstrated that the scalene and serratus muscles do not play any role in this phenomenon; it must therefore result from the action of intrinsic rib cage muscles.     

Respiratory mechanics and breathing pattern during and following maximal exercise

We looked for evidence of changes in lung elastic recoil and of inspiratory muscle fatigue at maximal exercise in seven normal subjects. Esophageal pressure, flow, and volume were measured during spontaneous breathing at increasing levels of cycle exercise to maximum. Total lung capacity (TLC) was determined at rest and immediately before exercise termination using a N2-washout technique. Maximal inspiratory pressure and inspiratory capacity were measured at 1-min intervals. The time course of instantaneous dynamic pressure of respiratory muscles (Pmus) was calculated for the spontaneous breaths immediately preceding exercise termination. TLC volume and lung elastic recoil at TLC were the same at the end of exercise as at rest. Maximum static inspiratory pressures at exercise termination were not reduced. However, mean Pmus of spontaneous breaths at end exercise exceeded 15% of maximum inspiratory pressure in five of the subjects. We conclude that lung elastic recoil is unchanged even at maximal exercise and that, while inspiratory muscles operate within a potentially fatiguing range, the high levels of ventilation observed during maximal exercise are not maintained for a sufficient time to result in mechanical fatigue.     

Effect of geniohyoid and sternohyoid muscle contraction on upper airway resistance in the cat.

Previous investigators (van Lunteren et al. J. Appl. Physiol. 62: 582-590, 1987) have suggested that the geniohyoid and sternohyoid muscles may act as upper airway dilators in the cat. To investigate the effect of geniohyoid and sternohyoid contraction on inspiratory upper airway resistance (UAR), we studied five adult male cats anesthetized with ketamine and xylazine during spontaneous room-air breathing. Inspiratory nasal airflow was measured by sealing the lips and constructing a nose mask. Supraglottic pressure was measured using a transpharyngeal catheter placed above the larynx. Mask pressure was measured using a separate catheter. Geniohyoid and sternohyoid lengths were determined by sonomicrometry. Geniohyoid and sternohyoid contraction was stimulated by direct muscle electrical stimulation with implanted wire electrodes. Mean inspiratory UAR was determined for spontaneous breaths under three conditions: 1) baseline (no muscle stimulation), 2) geniohyoid contraction alone, and 3) sternohyoid contraction alone. Geniohyoid contraction alone produced no significant reduction in inspiratory UAR [unstimulated, 17.75 +/- 0.86 (SE) cmH2O.l-1.s; geniohyoid contraction, 19.24 +/- 1.10]. Sternohyoid contraction alone also produced no significant reduction in inspiratory UAR (unstimulated, 15.74 +/- 0.92 cmH2O.l-1.s; sternohyoid contraction, 14.78 +/- 0.78). Simultaneous contraction of the geniohyoid and sternohyoid muscles over a wide range of muscle lengths produced no consistent change in inspiratory UAR. The geniohyoid and sternohyoid muscles do not appear to function consistently as upper airway dilator muscles when UAR is used as an index of upper airway patency in the cat.     

Physiological characterization of variability in response to lung volume reduction surgery.

This paper examines potential physiological mechanisms responsible for improvement after lung volume reduction surgery (LVRS). In 25 patients (63 +/- 9 yr; 11 men, 14 women), spirometry [forced expiratory volume in 1 s (FEV(1)) and forced vital capacity (FVC)], lung volumes [residual volume (RV) and total lung capacity (TLC)], small airway resistance, recoil pressures, and respiratory muscle contractility (RMC) were measured before and 4-6 mo after LVRS. Data were interpreted to assess how changes in each component of lung mechanics affect overall function. Among responders (DeltaFEV(1) > or = 12%; 150 ml), improvement was primarily due to an increase in FVC, not to FEV(1)-to-FVC ratio. Among nonresponders, FEV(1), FVC, and RV/TLC did not change after surgery, although recoil pressure increased in both groups. Both groups experienced a reduction in RMC after LVRS. In conclusion, LVRS improves function in emphysema by resizing the lung relative to the chest wall by reducing RV. LVRS does not change airway resistance but decreases RMC, which attenuates the potential benefits of LVRS that are generated by reducing RV/TLC. Among nonresponders, recoil pressure increased out of proportion to reduced volume, such that no increase in vital capacity or improvement in FEV(1) occurred.     

In vivo loads on airway smooth muscle: the role of noncontractile airway structures.

The degree of airway smooth muscle contraction and shortening that occurs in vivo is modified by many factors, including those that influence the degree of muscle activation, the resting muscle length, and the loads against which the muscle contracts. Canine trachealis muscle will shorten up to 70% of starting length from optimal length in vitro but will only shorten by around 30% in vivo. This limitation of shortening may be a result of the muscle shortening against an elastic load such as could be applied by tracheal cartilage. Limitation of airway smooth muscle shortening in smaller airways may be the result of contraction against an elastic load, such as could be applied by lung parenchymal recoil. Measurement of the elastic loads applied by the tracheal cartilage to the trachealis muscle and by lung parenchymal recoil to smooth muscle of smaller airways were performed in canine preparations. In both experiments the calculated elastic loads applied by the cartilage and the parenchymal recoil explained in part the limitation of maximal active shortening and airway narrowing observed. We conclude that the elastic loads provided by surrounding structures are important in determining the degree of airway smooth muscle shortening and the resultant airway narrowing.     

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.     

On the respiratory function of the ribs.

To assess the respiratory function of the ribs, we measured the changes in airway opening pressure (Pao) induced by stimulation of the parasternal and external intercostal muscles in anesthetized dogs, first before and then after the bony ribs were removed from both sides of the chest. Stimulating either set of muscles with the rib cage intact elicited a fall in Pao in all animals. After removal of the ribs, however, the fall in Pao produced by the parasternal intercostals was reduced by 60% and the fall produced by the external intercostals was eliminated. The normal outward curvature of the rib cage was also abolished in this condition, and when the curvature was restored by a small inflation, external intercostal stimulation consistently elicited a rise rather than a fall in Pao. These findings thus confirm that the ribs play a critical role in the act of breathing by converting intercostal muscle shortening into lung volume expansion. In addition, they carry the compression that is required to balance the pressure difference across the chest wall.     

Interaction between the canine diaphragm and intercostal muscles in lung expansion.

Changes in intrathoracic pressure produced by the various inspiratory intercostals are essentially additive, but the interaction between these muscles and the diaphragm remains uncertain. In the present study, this interaction was assessed by measuring the changes in airway opening (DeltaPao) or transpulmonary pressure (DeltaPtp) in vagotomized, phrenicotomized dogs during spontaneous inspiration (isolated intercostal contraction), during isolated rectangular or ramp stimulation of the peripheral ends of the transected C(5) phrenic nerve roots (isolated diaphragm contraction), and during spontaneous inspiration with superimposed phrenic nerve stimulation (combined diaphragm-intercostal contraction). With the endotracheal tube occluded at functional residual capacity, DeltaPao during combined diaphragm-intercostal contraction was nearly equal to the sum of the DeltaPao produced by the two muscle groups contracting individually. However, when the endotracheal tube was kept open, DeltaPtp during combined contraction was 123% of the sum of the individual DeltaPtp (P < 0.001). The increase in lung volume during combined contraction was also 109% of the sum of the individual volume increases (P < 0.02). Abdominal pressure during combined contraction was invariably lower than during isolated diaphragm contraction. It is concluded, therefore, that the canine diaphragm and intercostal muscles act synergistically during lung expansion and that this synergism is primarily due to the fact that the intercostal muscles reduce shortening of the diaphragm. When the lung is maintained at functional residual capacity, however, the synergism is obscured because the greater stiffness of the rib cage during diaphragm contraction enhances the DeltaPao produced by the isolated diaphragm and reduces the DeltaPao produced by the intercostal muscles.     

Interrupter technique for measurement of respiratory mechanics in anesthetized cats

In six spontaneously breathing anesthetized cats (pentobarbital sodium, 35 mg/kg ip), airflow, changes in lung volume, and tracheal and esophageal pressures were measured. Airflow was interrupted by brief airway occlusions during relaxed expirations (elicited via the Breuer-Hering inflation reflex) and throughout spontaneous breaths. A plateau in tracheal pressure occurred throughout relaxed expirations and the latter part of spontaneous expirations indicating respiratory muscle relaxation. Measurement of tracheal pressure, immediately preceding airflow, and corresponding volume enabled determination of respiratory system elastance and flow resistance. These were partitioned into lung and chest wall components using esophageal pressure. Respiratory system elastance was constant over the tidal volume range, divided approximately equally between the lung and chest wall. While the passive pressure-flow relationship for the respiratory system was linear, those for the lung and chest wall were curvilinear. Volume dependence of chest wall flow resistance was demonstrated. During inspiratory interruptions, tracheal pressure increased progressively; initial tracheal pressure was estimated by backward extrapolation. Inspiratory flow resistance of the lung and total respiratory system were constant. Force-velocity properties of the contracting inspiratory muscles contributed little to overall active resistance.     

Effect of inflation on the interaction between the left and right hemidiaphragms.

At resting end expiration [functional residual capacity (FRC)], the actions of the left and right hemidiaphragms on the lung are synergistic. However, the synergism decreases in magnitude as muscle tension decreases. Therefore, the hypothesis was tested in anesthetized dogs that the degree of synergism between the two hemidiaphragms also decreases with increasing lung volume. In a first experiment, the changes in airway opening pressure (DeltaPao) and abdominal pressure (DeltaPab) obtained during simultaneous stimulation of the left and right phrenic nerves (measured changes in pressure) at different lung volumes were compared with the sum of the pressure changes produced by their separate stimulation (predicted changes in pressure). Although the pressure changes decreased markedly with increasing lung volume, the measured DeltaPao and DeltaPab were substantially greater than the predicted values at all lung volumes. The ratio of the measured to the predicted DeltaPao, in fact, remained constant. In a second experiment, radiographic measurements showed that the fractional shortening of the muscle during bilateral contraction at high lung volumes was similar to that during unilateral contraction. During unilateral contraction at high lung volumes, however, the passive hemidiaphragm moved in the cranial direction, whereas, during unilateral contraction at FRC, it moved in the caudal direction. These observations indicate that 1) for a given muscle tension, the synergism between the two halves of the diaphragm is greater at high lung volumes than at FRC; and 2) this difference is primarily related to the greater distortion of the muscle configuration.