Genetic fate-mapping reveals surface accumulation but not deep organ invasion of pleural and peritoneal cavity macrophages following injury.

During injury, monocytes are recruited from the circulation to inflamed tissues and differentiate locally into mature macrophages, with prior reports showing that cavity macrophages of the peritoneum and pericardium invade deeply into the respective organs to promote repair. Here we report a dual recombinase-mediated genetic system designed to trace cavity macrophages in vivo by intersectional detection of two characteristic markers. Lineage tracing with this method shows accumulation of cavity macrophages during lung and liver injury on the surface of visceral organs without penetration into the parenchyma. Additional data suggest that these peritoneal or pleural cavity macrophages do not contribute to tissue repair and regeneration. Our in vivo genetic targeting approach thus provides a reliable method to identify and characterize cavity macrophages during their development and in tissue repair and regeneration, and distinguishes these cells from other lineages.

Estimation of change in pleural pressure in assisted and unassisted spontaneous breathing pediatric patients using fluctuation of central venous pressure: A preliminary study.

BACKGROUND: It is important to evaluate the size of respiratory effort to prevent patient self-inflicted lung injury and ventilator-induced diaphragmatic dysfunction. Esophageal pressure (Pes) measurement is the gold standard for estimating respiratory effort, but it is complicated by technical issues. We previously reported that a change in pleural pressure (ΔPpl) could be estimated without measuring Pes using change in CVP (ΔCVP) that has been adjusted with a simple correction among mechanically ventilated, paralyzed pediatric patients. This study aimed to determine whether our method can be used to estimate ΔPpl in assisted and unassisted spontaneous breathing patients during mechanical ventilation. METHODS: The study included hemodynamically stable children (aged <18 years) who were mechanically ventilated, had spontaneous breathing, and had a central venous catheter and esophageal balloon catheter in place. We measured the change in Pes (ΔPes), ΔCVP, and ΔPpl that was calculated using a corrected ΔCVP (cΔCVP-derived ΔPpl) under three pressure support levels (10, 5, and 0 cmH2O). The cΔCVP-derived ΔPpl value was calculated as follows: cΔCVP-derived ΔPpl = k × ΔCVP, where k was the ratio of the change in airway pressure (ΔPaw) to the ΔCVP during airway occlusion test. RESULTS: Of the 14 patients enrolled in the study, 6 were excluded because correct positioning of the esophageal balloon could not be confirmed, leaving eight patients for analysis (mean age, 4.8 months). Three variables that reflected ΔPpl (ΔPes, ΔCVP, and cΔCVP-derived ΔPpl) were measured and yielded the following results: -6.7 ± 4.8, - -2.6 ± 1.4, and - -7.3 ± 4.5 cmH2O, respectively. The repeated measures correlation between cΔCVP-derived ΔPpl and ΔPes showed that cΔCVP-derived ΔPpl had good correlation with ΔPes (r = 0.84, p< 0.0001). CONCLUSIONS: ΔPpl can be estimated reasonably accurately by ΔCVP using our method in assisted and unassisted spontaneous breathing children during mechanical ventilation.

Differential mechanisms are required for phrenic long-term facilitation over the course of motor neuron loss following CTB-SAP intrapleural injections.

Selective elimination of respiratory motor neurons using intrapleural injections of cholera toxin B fragment conjugated to saporin (CTB-SAP) mimics motor neuron death and respiratory deficits observed in rat models of neuromuscular diseases. This CTB-SAP model allows us to study the impact of motor neuron death on the output of surviving phrenic motor neurons. After 7(d) days of CTB-SAP, phrenic long-term facilitation (pLTF, a form of respiratory plasticity) is enhanced, but returns towards control levels at 28d. However, the mechanism responsible for this difference in magnitude of pLTF is unknown. In naïve rats, pLTF predominately requires 5-HT2 receptors, the new synthesis of BDNF, and MEK/ERK signaling; however, pLTF can alternatively be induced via A2A receptors, the new synthesis of TrkB, and PI3K/Akt signaling. Since A2A receptor-dependent pLTF is enhanced in naïve rats, we suggest that 7d CTB-SAP treated rats utilize the alternative mechanism for pLTF. Here, we tested the hypothesis that pLTF following CTB-SAP is: 1) TrkB and PI3K/Akt, not BDNF and MEK/ERK, dependent at 7d; and 2) BDNF and MEK/ERK, not TrkB and PI3K/Akt, dependent at 28d. Adult Sprague Dawley male rats were anesthetized, paralyzed, ventilated, and were exposed to acute intermittent hypoxia (AIH; 3, 5 min bouts of 10.5% O2) following bilateral, intrapleural injections at 7d and 28d of: 1) CTB-SAP (25 µg), or 2) un-conjugated CTB and SAP (control). Intrathecal C4 delivery included either: 1) small interfering RNA that targeted BDNF or TrkB mRNA; 2) UO126 (MEK/ERK inhibitor); or 3) PI828 (PI3K/Akt inhibitor). Our data suggest that pLTF in 7d CTB-SAP treated rats is elicited primarily through TrkB and PI3K/Akt-dependent mechanisms, whereas BDNF and MEK/ERK-dependent mechanisms induce pLTF in 28d CTB-SAP treated rats. This project increases our understanding of respiratory plasticity and its implications for breathing following motor neuron death.

Determinants of the esophageal-pleural pressure relationship in humans.

Esophageal pressure has been suggested as adequate surrogate of the pleural pressure. We investigate after lung surgery the determinants of the esophageal and intrathoracic pressures and their differences. The esophageal pressure (through esophageal balloon) and the intrathoracic/pleural pressure (through the chest tube on the surgery side) were measured after surgery in 28 patients immediately after lobectomy or wedge resection. Measurements were made in the nondependent lateral position (without or with ventilation of the operated lung) and in the supine position. In the lateral position with the nondependent lung, collapsed or ventilated, the differences between esophageal and pleural pressure amounted to 4.4 ± 1.6 and 5.1 ± 1.7 cmH2O. In the supine position, the difference amounted to 7.3 ± 2.8 cmH2O. In the supine position, the estimated compressive forces on the mediastinum were 10.5 ± 3.1 cmH2O and on the iso-gravitational pleural plane 3.2 ± 1.8 cmH2O. A simple model describing the roles of chest, lung, and pneumothorax volume matching on the pleural pressure genesis was developed; modeled pleural pressure = 1.0057 × measured pleural pressure + 0.6592 (r2 = 0.8). Whatever the position and the ventilator settings, the esophageal pressure changed in a 1:1 ratio with the changes in pleural pressure. Consequently, chest wall elastance (Ecw) measured by intrathoracic (Ecw = ΔPpl/tidal volume) or esophageal pressure (Ecw = ΔPes/tidal volume) was identical in all the positions we tested. We conclude that esophageal and pleural pressures may be largely different depending on body position (gravitational forces) and lung-chest wall volume matching. Their changes, however, are identical.NEW & NOTEWORTHY Esophageal and pleural pressure changes occur at a 1:1 ratio, fully justifying the use of esophageal pressure to compute the chest wall elastance and the changes in pleural pressure and in lung stress. The absolute value of esophageal and pleural pressures may be largely different, depending on the body position (gravitational forces) and the lung-chest wall volume matching. Therefore, the absolute value of esophageal pressure should not be used as a surrogate of pleural pressure.

Asymmetrical intrapleural pressure distribution: a cause for scoliosis? A computational analysis.

PURPOSE: The mechanical link between the pleural physiology and the development of scoliosis is still unresolved. The intrapleural pressure (IPP) which is distributed across the inner chest wall has yet been widely neglected in etiology debates. With this study, we attempted to investigate the mechanical influence of the IPP distribution on the shape of the spinal curvature. METHODS: A finite element model of pleura, chest and spine was created based on CT data of a patient with no visual deformities. Different IPP distributions at a static end of expiration condition were investigated, such as the influence of an asymmetry in the IPP distribution between the left and right hemithorax. The results were then compared to clinical data. RESULTS: The application of the IPP resulted in a compressive force of 22.3 N and a flexion moment of 2.8 N m at S1. An asymmetrical pressure between the left and right hemithorax resulted in lateral deviation of the spine towards the side of the reduced negative pressure. In particular, the pressure within the dorsal section of the rib cage had a strong influence on the vertebral rotation, while the pressure in medial and ventral region affected the lateral displacement. CONCLUSIONS: An asymmetrical IPP caused spinal deformation patterns which were comparable to deformation patterns seen in scoliotic spines. The calculated reaction forces suggest that the IPP contributes in counterbalancing the weight of the intrathoracic organs. The study confirms the potential relevance of the IPP for spinal biomechanics and pathologies, such as adolescent idiopathic scoliosis.

The use of a virtual patient to follow pleural pressure changes associated with therapeutic thoracentesis.

PURPOSE: Influence of therapeutic thoracentesis on the pleural pressure (Pp) has been discussed in many clinical studies, however reasons of Pp changes are not precisely established. The aim of the study was to use a previously elaborated virtual cardiopulmonary patient (VP) in analysis of impact of physiological factors on Pp during the procedure. METHODS: Simulations were performed on VP with default values of parameters for which VP simulated the respiratory system of the average 50-year-old healthy Polish woman according to spirometric examination. Alterations of Pp and the amplitude of Pp changes related to breathing (AP) were analyzed. Model parameters related to chosen factors were deviated from their default values to analyze the degree of their impact on Pp and AP. The analysis was based on and supported by our own clinical data. RESULTS: The Pp and AP alteration intensity appeared to be most sensitive to the compliances of the rib cage and mediastinum, and the nonlinearity of the dependence between the recoil pressure and the lung volume: the lower the compliances and the higher the nonlinearity were, the deeper the Pp fall during the procedure and the bigger the AP increase were observed. CONCLUSIONS: Experiments in silico are very useful in analyzing sophisticated physiological and medical problems. They made it possible to show which factors are particularly responsible for changes in Pp during thoracentesis. In the future, they may be useful in establishing objective conditions under which thoracentesis needs to be stopped.

Action of the diaphragm on the rib cage.

When the diaphragm contracts, pleural pressure falls, exerting a caudal and inward force on the entire rib cage. However, the diaphragm also exerts forces in the cranial and outward direction on the lower ribs. One of these forces, the "insertional force," is applied by the muscle at its attachments to the lower ribs. The second, the "appositional force," is due to the transmission of abdominal pressure to the lower rib cage in the zone of apposition. In the control condition at functional residual capacity, the effects of these two forces on the lower ribs are nearly equal and outweigh the effect of pleural pressure, whereas for the upper ribs, the effect of pleural pressure is greater. The balance between these effects, however, may be altered. When the abdomen is given a mechanical support, the insertional and appositional forces are increased, so that the muscle produces a larger expansion of the lower rib cage and, with it, a smaller retraction of the upper rib cage. In contrast, at higher lung volumes the zone of apposition is decreased, and pleural pressure is the dominant force on the lower ribs as well. Consequently, although the force exerted by the diaphragm on these ribs remains inspiratory, rib displacement is reversed into a caudal-inward displacement. This mechanism likely explains the inspiratory retraction of the lateral walls of the lower rib cage observed in many subjects with chronic obstructive pulmonary disease (Hoover's sign). These observations support the use of a three-compartment, rather than a two-compartment, model to describe chest wall mechanics.

Development of a model to mimic pleural space mechanics.

BACKGROUND: A simulator of the respiratory system which includes the pleural space is currently lacking. However, such mechanical models are essential to develop and test new medical devices regulating the pressure in the pleural space. OBJECTIVE: It was the aim of this study to develop a model which mimics the pleural space. The device should be able to represent biomechanical functions of the respiratory system and it is intended for applications in research and development to study pleural space mechanics. The system should allow adjusting parameters to simulate different kinds of breathing. Output parameters such as the pressure in pleural cavity or the breathing volume should be measured. METHODS: A mechanical lung simulator was developed. The chest wall is represented by an elastic shell in which silicone balloons were implemented to mimic the lung tissue. These two components establish a pleural cavity. Pressure sensors were installed to measure pressure in the pleural space and an aeroplethysmograph was positioned above the two lungs to measure flow. The system was assembled and tested under various conditions. RESULTS: Different tests demonstrated that the device is currently capable of simulating breathing volumes up to approx. 1700 ml. Different breathing characteristics including coughing can be simulated. Higher negative pressures especially during deep breathing were observed at the top of the lung because of higher balloon wall (lung) thickness in this area. It was possible to demonstrate the effect of certain changes of the lung tissue such as fibrosis with corresponding pressure recordings confirming known effects of such pathologies. CONCLUSIONS: The device allows simulating pressures in the pleural space during breathing at an advanced level and will be of use to develop and validate medical devices under laboratory conditions that control and regulate the pleural space. This represents a significant benefit to improve the development process for devices in this area.

Pleural function and lymphatics.

The pleural space plays an important role in respiratory function as the negative intrapleural pressure regimen ensures lung expansion and in the mean time maintains the tight mechanical coupling between the lung and the chest wall. The efficiency of the lung-chest wall coupling depends upon pleural liquid volume, which in turn reflects the balance between the filtration of fluid into and its egress out of the cavity. While filtration occurs through a single mechanism passively driving fluid from the interstitium of the parietal pleura into the cavity, several mechanisms may co-operate to remove pleural fluid. Among these, the pleural lymphatic system emerges as the most important one in quantitative terms and the only one able to cope with variable pleural fluid volume and drainage requirements. In this review, we present a detailed account of the actual knowledge on: (a) the complex morphology of the pleural lymphatic system, (b) the mechanism supporting pleural lymph formation and propulsion, (c) the dependence of pleural lymphatic function upon local tissue mechanics and (d) the effect of lymphatic inefficiency in the development of clinically severe pleural and, more in general, respiratory pathologies.

Esophageal pressure: benefit and limitations.

The recording of esophageal pressure (Pes) in supine position as a substitute for pleural pressure is difficult and fraught with potential errors. Pes is affected by the: 1) elastance and weight of the lung; 2) elastance and weight of the rib cage; 3) weight of the mediastinal organs; 4) elastance and weight of the diaphragm and abdomen; 5) elastance of the esophageal wall; and 6) elastance of the esophageal balloon (if filled with too much air). If the purpose is to measure lung compliance in the intensive care patient, reasonably useful information might be obtained by measuring airway pressure alone, considering chest wall compliance to be a weight that is forced away by the ventilation. Such weight requires a constant pressure for displacement. The transpulmonary pressure, whether calculated with Pes or by another measure of abdominal pressure, may guide in PEEP titration. It may also enable calculation of stresses applied to the lung and these may be more important in guiding an optimal ventilator setting than an optimum compliance or oxygenation of blood. Diaphragm function can be estimated by esophageal minus gastric pressure and with even more precision, when combined with diaphragm electromyography.

[Production and law of variation of the pleural cavity intrinsic pressure and the pressure of alveolar wall during respiratory process].

All physiologic textbooks deal with pleural cavity pressure, alveolar wall pressure and pressure inside the lung, but they have not stated these ideas clearly. The present study reveals production and Law of variation of the intrinsic pressure of pleural cavity, the pressure of alveolar wall and the intrinsic pressure in the alveoli. Pleural cavity intrinsic pressure is produced by the pressure from pleura expanding or compressing force of the lungs. When the lungs calmly inhale, the thorax expands, pleural cavity negative pressure increase. When the lungs calmly exhale, thorax reduces, but thorax and lungs are still in the extended state, pleural cavity is still in negative pressure. With thorax reducing, negative pressure decreases. When the lungs are at the forced expiration, the lung pleura and wall pleura extrude pleural cavity, only to produce positive pressure. The pressure of alveolar wall is the algebraic sum of the intrinsic pressure of pleural cavity, the intrinsic pressure of pulmonary tissue and the additional pressure of alveolar wall. We did the calculation of additional pressure on the alveolar wall by using Laplace formula of spherical elastic membrane. The intrinsic pressure of alveoli depends on the moving speed or slowness of expansion or compression of alveolar wall and the size of trachea resistance.

Digital and smart chest drainage systems to monitor air leaks: the birth of a new era?

Recently, several companies have manufactured and commercialized new pleural drainage units that incorporate electronic components for the digital quantification of air through chest tubes and, in some instances, pleural pressure assessment. The goal of these systems is to objectify this previously subjective bedside clinical parameter and allow for more objective, consistent measurement of air leaks. The belief is this will lead to quicker and more accurate chest tube management. In addition, some systems feature portable suction devices. These may afford earlier mobilization of patients because the pleural drainage chamber is attached to a battery-powered smart suction device. In this article we review the clinical experiences using these new devices.

Hybrid cardiopulmonary model for analysis of valsalva maneuver with radial artery pulse.

A comprehensive model, which has the advantages of both lumped parameter and distributed parameter, has been developed with the objective of investigating the respiratory influences in radial artery pressure pulse as in photoplethysmography (PPG). It integrates lumped parameter cardiopulmonary (CP) model and transmission line arterial tree model from aorta to radial artery. The cardio-pulmonary interaction is realized by incorporating respiratory-induced variations in intrapleural pressure (Ppl) in circulatory system. The PPG signal of the model is considered as the radial artery pulse. To investigate the interaction Valsalva Maneuver (VM) condition has been simulated for different Ppl magnitude (10, 20, 30, and 40 mmHg) and for different time duration (5, 10, 15, and 20 s), and validated with PPG signal recorded in 10 normal subjects performing VM. The effects of test duration and VM pressure are studied in both the simulation and the experiments with specific focus on the maximal (%∆) changes in Heart Rate (HR), and Mean Arterial Pressure (MAP) during phases II and IV of VM. The correlation coefficients derived from model result have good agreement with experimental results. As radial artery pulse plays important role in both allopathy and alternate medicine systems, this model can serve to study its clinical importance in detecting cardiac and respiratory pathologies.

Effect of acute inflation on the mechanics of the inspiratory muscles.

When the lung is inflated acutely, the capacity of the diaphragm to generate pressure, in particular pleural pressure (Ppl), is impaired because the muscle during contraction is shorter and generates less force. At very high lung volumes, the pressure-generating capacity of the diaphragm may be further reduced by an increase in the muscle radius of curvature. Lung inflation similarly impairs the pressure-generating capacity of the inspiratory intercostal muscles, both the parasternal intercostals and the external intercostals. In contrast to the diaphragm, however, this adverse effect is largely related to the orientation and motion of the ribs, rather than the ability of the muscles to generate force. During combined activation of the two sets of muscles, the change in Ppl is larger than during isolated diaphragm activation, and this added load on the diaphragm reduces the shortening of the muscle and increases muscle force. In addition, activation of the diaphragm suppresses the cranial displacement of the passive diaphragm that occurs during isolated intercostal contraction and increases the respiratory effect of the intercostals. As a result, the change in Ppl generated during combined diaphragm-intercostal activation is greater than the sum of the pressures generated during separate muscle activation. Although this synergistic interaction becomes particularly prominent at high lung volumes, lung inflation, either bilateral or unilateral, places a substantial stress on the inspiratory muscle pump.

Role of pleural pressure in the coupling between the intercostal muscles and the ribs.

The inspiratory intercostal muscles elevate the ribs and thereby elicit a fall in pleural pressure (DeltaPpl) when they contract. In the present study, we initially tested the hypothesis that this DeltaPpl does, in turn, oppose the rib elevation. The cranial rib displacement (Xr) produced by selective activation of the parasternal intercostal muscle in the fourth interspace was measured in dogs, first with the rib cage intact and then after DeltaPpl was eliminated by bilateral pneumothorax. For a given parasternal contraction, Xr was greater after pneumothorax; the increase in Xr per unit decrease in DeltaPpl was 0.98+/-0.11 mm/cmH2O. Because this relation was similar to that obtained during isolated diaphragmatic contraction, we subsequently tested the hypothesis that the increase in Xr observed during breathing after diaphragmatic paralysis was, in part, the result of the decrease in DeltaPpl, and the contribution of the difference in DeltaPpl to the difference in Xr was determined by using the relation between Xr and DeltaPpl during passive inflation. With diaphragmatic paralysis, Xr during inspiration increased approximately threefold, and 47+/-8% of this increase was accounted for by the decrease in DeltaPpl. These observations indicate that 1) DeltaPpl is a primary determinant of rib motion during intercostal muscle contraction and 2) the decrease in DeltaPpl and the increase in intercostal muscle activity contribute equally to the increase in inspiratory cranial displacement of the ribs after diaphragm paralysis.

Regional recruitment of rat diaphragmatic lymphatics in response to increased pleural or peritoneal fluid load.

The specific role of the diaphragmatic tendinous and muscular tissues in sustaining lymph formation and propulsion in the diaphragm was studied in 24 anaesthetized spontaneously breathing supine rats. Three experimental protocols were used: (a) control; (b) peritoneal ascitis, induced through an intraperitoneal injection of 100 ml kg(-1) of iso-oncotic saline; and (c) pleural effusion, induced through an intrapleural injection of 6.6 ml kg(-1) saline solution. A group of animals (n = 12) was instrumented to measure the hydraulic transdiaphragmatic pressure gradient between the pleural and peritoneal cavities in the three protocols. In the other group (n = 12), the injected iso-oncotic saline was enriched with 2% fluorescent dextrans (molecular mass = 70 kDa); at 30 min from the injections these animals were suppressed and their diaphragm excised and processed for confocal microscopy analysis. In control conditions, in spite of a favourable peritoneal-to-pleural pressure gradient, the majority of the tracer absorbed into the diaphragmatic lymphatic system converges towards the deeper collecting lymphatic ducts. This suggests that diaphragmatic lymph formation mostly depends upon pressure gradients developing between the serosal cavities and the lymphatic vessel lumen. In addition, the tracer distributes to lymph vessels located in the muscular diaphragmatic tissue, suggesting that active muscle contraction, rather than passive tendon stretch, more efficiently enhances local diaphragmatic lymph flow. Vice versa, a prevailing recruitment of the lymphatics of the tendinous diaphragmatic regions was observed in peritoneal ascitis and pleural effusion, suggesting a functional adaptation of the diaphragmatic network to increased draining requirements.

Telemetric recording of intrapleural pressure.

BACKGROUND: Monitoring of intrapleural pressure (IPP) is used for evaluation of lung function in a number of pathophysiological conditions. We describe a telemetric method of non-invasive monitoring of the IPP in conscious animals intermittently or continuously for a prolonged period of time. MATERIALS AND METHODS: After IACUC approval, six mongrel dogs were used for the study. After sedation, each dog was intubated and anesthetized using 0.5% Isoflurane. A telemetric implant model TL11M2-D70-PCT from Data Science International was secured subcutaneously. The pressure sensor tip of the catheter from the implant was inserted into the pleural space, and the catheter was secured with sutures. The IPP signals were recorded at a sampling rate of 100 points/second for 30 to 60 min daily for 4 days. From these recordings, the total mean negative IPP (mmHg), and the total mean negative IPP for a standard time of 30 min were calculated. In addition, the actual inspiratory and expiratory pressures were also measured from stable recording of the IPP waveforms. RESULTS: In six dogs, the total mean +/- SD negative IPP was -10.8 +/- 10.6 mmHg. After normalizing with respect to acquisition time it was -13.2 +/- 11.2 mmHg/min. The actual inspiratory pressure was -19.7 +/- 15.3, and the expiratory pressure was -11.0 +/- 12.9. CONCLUSIONS: Our study demonstrates that telemetric monitoring of IPP can be performed reliably and non-invasively in conscious experimental animals. The values for IPP in our study are compatible with the results of other investigators who used different methods of IPP measurement. Further work may show this method to be helpful in understanding the pathophysiology of various breathing disorders.

Manual vibration increases expiratory flow rate via increased intrapleural pressure in healthy adults: an experimental study.

QUESTION: What is the relationship between vibration of the chest wall and the resulting chest wall force, chest wall circumference,intrapleural pressure, and expiratory flow rate? Is the change in intrapleural pressure during vibration the sum of the intrapleural pressure due to recoil of the lung, chest wall compression, and chest wall oscillation? DESIGN: Randomised, within-subject,experimental study. PARTICIPANTS: Seven experienced cardiopulmonary physiotherapists and three healthy adults. INTERVENTION: Vibration (compression + oscillation), compression alone, and oscillation alone were applied manually to the chest walls of healthy participants during passive exertion and compared with passive expiration alone. OUTCOME MEASURES: Chest wall force, chest wall circumference, intrapleural pressure, and expiratory flow rate. RESULTS: During vibration, coherence was high(r2 > 0.97) between external chest wall force, chest wall circumference, intrapleural pressure, and expiratory flow. The mean change in intrapleural pressure during vibration was 9.55 cmH2O (SD 1.66), during chest compression alone was 8.06 cmH2O(SD 1.65), during oscillation alone was 7.93 cmH2O (SD 1.57), and during passive expiration alone was 6.82 cmH2O (SD 1.51). During vibration, compression contributed 13% of the change in intrapleural pressure, oscillation contributed 12%, and lung recoil contributed the remaining 75%. CONCLUSIONS: During vibration the chest behaves as a highly linear system. Changes in intrapleural pressure occurring during vibration appear to be the sum of changes in pressure due to lung recoil and the compressive and oscillatory components of the technique, which suggests that all three components are required to optimise expiratory flow.

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.