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The explanation for prone and supine differences in tissue density and pleural pressure gradients in the healthy lung has been inferred from several studies as compression of dependent tissue by the heart in the supine posture; however, this hypothesis has not been directly confirmed. Differences could also arise from change in shape of the chest wall and diaphragm, and because of shape with respect to gravity. The contribution of this third mechanism is explored here. Tissue density and static elastic recoil were estimated in the supine and prone left human lung at functional residual capacity using a finite-element analysis. Supine model geometries were derived from multidetector row computed tomography imaging of two subjects: one normal ( subject 1), and one with small airway disease ( subject 2). For each subject, the prone model was the supine lung shape with gravity reversed; therefore, the prone model was isolated from the influence of displacement of the diaphragm, chest wall, or heart. Model estimates were validated against multidetector row computed tomography measurement of regional density for each subject supine and an independent study of the prone and supine lung. The magnitude of the gradient in density supine (−4.33%/cm for subject 1, and −4.96%/cm for subject 2) was nearly twice as large as for the prone lung (−2.72%/cm for subject 1, and −2.51%/cm for subject 2), consistent with measurements in dogs. The corresponding pleural pressure gradients were 0.54 cmH2O/cm ( subject 1) and 0.56 cmH2O/cm ( subject 2) for supine, and 0.29 cmH2O/cm ( subject 1) and 0.27 cmH2O/cm ( subject 2) for prone. A smaller prone gradient was predicted without shape change of the “container” or support of the heart by the lung. The influence of the heart was to constrain the shape in which the lung deformed.

Respiratory symptoms accompanying pleural diseases combine dyspnea, tachypnea, rapid shallow breathing, and sometimes hypotension. There are no experimental data on the changes in respiratory and circulatory functions elicited by the activation of pleural afferents. After removal of all muscles covering the 5th to 10th intercostal spaces, we investigated in paralyzed, vagotomized rabbits the changes in phrenic discharge, transpulmonary pressure, and systemic arterial pressure in response to an outwardly directed force exerted on the parietal pleura or the local application of solutions containing lactic acid or inflammatory mediators. Mechanical stimulation of the pleura induced an immediate decrease in both integrated phrenic discharge and arterial blood pressure, the responses being positively correlated with the magnitude of force applied on the pleura. No accompanying changes in ventilatory timing, transpulmonary pressure, or heart rate were measured. Lactic acid solution also elicited an inhibition of phrenic activity and a fall in blood pressure. Section of the internal intercostal nerves supplying the stimulated intercostal spaces totally abolished the responses to mechanical stimulation or lactic acid. An inflammatory mixture elicited only modest respiratory and circulatory effects. We concluded that an acute mechanical distension of the parietal pleura as well as its chemical stimulation by lactic acid elicit a marked inhibition of phrenic motoneurons combined to a reduction of the sympathetic outflow to the circulatory system.

Cellular remodeling during angiogenesis in the lung is poorly described. Furthermore, it is the systemic vasculature of the lung and surrounding the lung that is proangiogenic when the pulmonary circulation becomes impaired. In a mouse model of chronic pulmonary thromboembolism, after left pulmonary artery ligation (LPAL), the intercostal vasculature, in proximity to the ischemic lung, proliferates and invades the lung ( 12 ). In the present study, we performed a detailed investigation of the kinetics of remodeling using histological sections of the left lung of C57Bl/6J mice after LPAL (4 h to 20 days) or after sham surgery. New vessels were seen within the thickened visceral pleura 4 days after LPAL predominantly in the upper portion of the left lung. Connections between new vessels within the pleura and pulmonary capillaries were clearly discerned by 7 days after LPAL. The visceral pleura and the lung parenchyma showed intense tissue remodeling, as evidenced by markedly elevated levels of both proliferating cell nuclear antigen and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling positive cells. Rapidly dividing cells were predominantly macrophages and type II pneumocytes. The increased apoptotic activity was further quantified by caspase-3 activity, which showed a sixfold increase relative to naive lungs, by 24 h after LPAL. Because sham surgeries had little effect on measured parameters, we conclude that both thoracic wound healing and pulmonary ischemia are required for systemic neovascularization.

To address the role of the parietal pleura in reduction of mesothelial shear stresses during breathing, we measured the stiffness of the parietal pleural surface of mammalian chest walls using microindentation. The pleural surface was indented over ribs and intercostal spaces with rigid flat punches (tip radii of 0.01, 0.02, and 0.1 cm) to probe stiffness at length scales comparable with those of surface asperities. We found a tissue shear modulus of 6,700 dyn/cm2 and pleural membrane tension of 4,900 dyn/cm, with a geometric standard deviation of 0.42. These values are similar to those measured for the lung by Hajji et al., using indentation (Hajji MA, Wilson TA, and Lai-Fook SJ. J Appl Physiol Respirat Environ Exerc Physiol 47: 175–181, 1979). Surprisingly, the pleural surface over ribs and intercostal spaces exhibited similar stiffness. In addition, caudal regions exhibited lower stiffness than cranial regions. In the context of elastohydrodynamic lubrication, these results suggest that shear-induced pressures during breathing deform the chest wall and lung surfaces to a similar extent, promoting spatial uniformity of pleural fluid thickness and reducing shear stresses.

The present study was undertaken to gain further insight into the mechanisms responsible for the sustained active expiratory upper airway closure previously observed during high-permeability pulmonary edema in lambs. The experiments were conducted in nonsedated lambs, in which airflow and thyroarytenoid and inferior pharyngeal constrictor muscle electromyographic activity were recorded. We first studied the consequences of hemodynamic pulmonary edema (induced by impeding pulmonary venous return) on upper airway dynamics in five lambs; under this condition, a sustained expiratory upper airway closure consistently appeared. We then tested whether expiratory upper airway closure was related to vagal afferent activity from bronchopulmonary receptors. Five bivagotomized lambs underwent high-permeability pulmonary edema: no sustained expiratory upper airway closure was observed. Finally, we studied whether a sustained decrease in lung volume induced a sustained expiratory upper airway closure. Five lambs underwent a 250-ml pleural infusion: no sustained expiratory upper airway closure was observed. We conclude that 1) the sustained expiratory upper airway closure observed during pulmonary edema in nonsedated lambs is related to stimulation of vagal afferents by an increase in lung water and 2) a decrease in lung volume does not seem to be the causal factor.

Dynamic collapse of the pulmonary airways, leading to flow limitation, is a significant event in a number of respiratory pathologies, including obstructive sleep apnea syndrome and chronic obstructive pulmonary disease. Quantitative evaluation of the mechanical status of the respiratory system in these conditions provides useful insights into airway caliber and tissue stiffness, which are hallmarks of such abnormalities. However, assessing respiratory mechanics in the presence of flow limitation is problematic because the single-compartment linear model on which most assessment methods are based is not valid over the entire breath. Indeed, even deciding which parts of a breath are flow limited from measurement of mouth flow and pleural pressure often proves to be difficult. In this study, we investigated the use of two approaches to assessing the overall mechanical properties of the respiratory system in the presence of inspiratory flow limitation. The first method is an adaptation of the classic Mead-Whittenberger method, and the second method is based on information-weighted histograms obtained from recursively estimated signals of respiratory resistance and elastance. We tested the methods on data simulated by using a computer model of the respiratory system and on data collected from obese sleeping pigs. We found that the information-weighted histograms provided the more robust overall estimates of respiratory mechanics.

Schneider, H., C. D. Schaub, K. A. Andreoni, A. R. Schwartz, R. L. Smith, J. L. Robotham, and C. P. O’Donnell. Systemic and pulmonary hemodynamic responses to normal and obstructed breathing during sleep. J. Appl. Physiol. 83(5): 1671–1680, 1997.—We examined the hemodynamic responses to normal breathing and induced upper airway obstructions during sleep in a canine model of obstructive sleep apnea. During normal breathing, cardiac output decreased (12.9 ± 3.5%, P < 0.025) from wakefulness to non-rapid-eye-movement sleep (NREM) but did not change from NREM to rapid-eye-movement (REM) sleep. There was a decrease ( P < 0.05) in systemic (7.2 ± 2.1 mmHg) and pulmonary (2.0 ± 0.6 mmHg) arterial pressures from wakefulness to NREM sleep. In contrast, systemic (8.1 ± 1.0 mmHg, P < 0.025), but not pulmonary, arterial pressures decreased from NREM to REM sleep. During repetitive airway obstructions (56.0 ± 4.7 events/h) in NREM sleep, cardiac output (17.9 ± 3.1%) and heart rate (16.2 ± 2.5%) increased ( P < 0.05), without a change in stroke volume, compared with normal breathing during NREM sleep. During single obstructive events, left (7.8 ± 3.0%, P < 0.05) and right (7.1 ± 0.7%, P < 0.01) ventricular outputs decreased during the apneic period. However, left (20.7 ± 1.6%, P < 0.01) and right (24.0 ± 4.2%, P < 0.05) ventricular outputs increased in the postapneic period because of an increase in heart rate. Thus 1) the systemic, but not the pulmonary, circulation vasodilates during REM sleep with normal breathing; 2) heart rate, rather than stroke volume, is the dominant factor modulating ventricular output in response to apnea; and 3) left and right ventricular outputs oscillate markedly and in phase throughout the apnea cycle.

Butler, James P., Hiroshi Miki, Stephanie Squarcia, Rick A. Rogers, and John L. Lehr. Effect of macroscopic deformation on lung microstructure. J. Appl. Physiol.81(4): 1792–1799, 1996.—Using an anisotropic theory of diffuse light scattering in lungs, we measured the fractional changes in geometric mean linear intercepts in orthogonal directions when freshly excised rabbit lungs were subjected to isovolume uniaxial strains. Results from the optical technique were compared with morphometric estimates of fractional changes in mean linear intercepts from the same strained and unstrained (control) lobes, with the conclusion that diffuse light scattering is adequate to estimate changes in mean free paths in different directions. We compared optical estimates of fractional changes in mean linear intercepts with the macroscopic strain field measured by displacements of pleural markers; this relationship did not significantly differ from the line of identity. We conclude that the microscopic strain field is closely matched to the macroscopic strain field during uniaxial distortion. This suggests that surface reorientation may not play a large role in the origin of the low shear modulus of the lung, but this cannot be definitively stated without comparison of these experimental results to specific model predictions of the changes in mean linear intercepts in shear deformation.

We propose a new model of pleural liquid mechanics in the apneic animal based on the observation that the lung, in its position within the serous fluid of the chest, is a buoyant object with few physical connections to the chest. The buoyancy force due to the lung's low density causes the lung to rise within the chest, which in turn causes fluid to be squeezed out from the regions above the lung. The result is the transient component of the downward flow of intrapleural liquid and the less-than-hydrostatic vertical intrapleural pressure gradient observed by other investigators. For the purposes of mathematical simplicity, we have modeled the lung and chest wall of a horizontal animal as a pair of concentric cylinders separated by a narrow gap representing the pleural space. In this first version of the model, we treat the pleurae of the lung and chest wall as impermeable rigid boundaries, but despite these limitations, our mathematical analysis agrees with observations from a number of groups and explains the flow direction from top to bottom as well as the reported changes in vertical pressure gradient in response to a change in body orientation.

The purpose of this study was to see whether there are developmental differences in the protein permeability of the pulmonary circulation that might contribute to the abnormal lung fluid balance seen in premature lambs with respiratory failure. In one series of experiments, we measured albumin turnover time, which reflects the escape rate of radiolabeled albumin from the pulmonary circulation, of five preterm fetal lambs (125 +/- 1 days gestation) and five newborn lambs (19 +/- 9 days old). Turnover time was not significantly different in fetuses (160 +/- 38 min) and newborns (141 +/- 54 min), implying a similar protein permeability of the pulmonary circulation. In additional experiments, we measured pulmonary hemodynamic and lung lymph flow responses to intravenous saline infusion in seven preterm fetal lambs (130 +/- 3 days gestation) and seven newborn lambs (14 +/- 3 days old). During saline infusion, calculated fluid filtration pressure increased by a similar amount in fetuses and newborns (3.4 +/- 0.8 and 2.8 +/- 0.9 Torr, respectively), resulting in a similar change in lung lymph flow in fetuses and newborns (0.59 +/- 0.27 and 0.55 +/- 0.25 ml.h-1.kg body wt-1, respectively). The results of these studies indicate that protein permeability of the pulmonary circulation does not change significantly during late fetal and early postnatal development.

We used computed tomography (CT) to examine the effects of infusing 60 ml/kg of saline into the pleural space of four anesthetized paralyzed dogs ventilated with a constant tidal volume at a positive end-expiratory pressure of 0.5 kPa. The dogs were positioned supine, and the thoracic cavity was scanned from apex to base before and immediately after effusate loading. Each CT image was analyzed semi-automatically on a 486 personal computer with custom-designed software. We found that, despite right-side infusion, the effusate was distributed bilaterally no doubt because of the incomplete canine mediastinum. In general, the volume change of the lung was one-third and that of the chest wall was two-thirds that of the total volume infused. Most of the lung volume was contained in the caudal one-third of the lung pre-effusion, and most of the lung volume loss due to effusion was from this same region. Chest wall volume increased and in a more uniform manner post-effusion. The decrease in lung volume resulted in an increase in the mean density of the lung and an increase in its vertical density gradient as the lung was lifted upward toward the sternum by the effusate. The lung lost vertical height while the chest wall increased both its vertical and lateral dimensions after effusate loading. These results suggest that expansion of the chest wall helps preserve lung volume in the presence of acute pleural effusion. We have also demonstrated that CT is a useful tool for assessing changes in volume, shape, and density of the respiratory system.

The permselectivity of the parietal pleura was determined in spontaneously breathing anesthetized rabbits and dogs. In rabbits, we injected intrapleurally 5 ml of 1-g/dl albumin solution containing 100 microCi of 131I-labeled albumin plus 100 microCi of either lactate dehydrogenase (LDH) or alpha 2–125I-macroglobulin. Dogs received 100 ml of 1-g/dl albumin solution containing 100 microCi of 131I-albumin plus 100 microCi of alpha 2–125I-macroglobulin. A transpleural pressure gradient was set, lowering the intracapsular pressure to -30 cmH2O. The solvent drag reflection coefficients (sigma f) were calculated as the ratio between tracer concentrations in capsular and pleural liquid collected at 60–180 min. In rabbits sigma f was 0.44 +/- 0.2 (SD) for albumin, 0.84 +/- 0.1 for LDH, and 0.93 +/- 0.05 for alpha 2-macroglobulin. In dogs sigma f was 0.30 +/- 0.19 for albumin and 0.53 +/- 0.15 for alpha 2-macroglobulin. The hydraulic conductivity of the parietal pleura was 2.18 +/- 1.54 microliters.h-1.cmH2O-1.cm-2 in rabbits and 1.22 +/- 1.13 microliters.h-1.cmH2O-1.cm-2 in dogs. The parietal pleura could be modeled by two pore populations with radii of 83–89 and 156-222 A. The permeability coefficient averaged 0.08–0.21 x 10(-6) cm/s for albumin, 0.06–0.09 x 10(-6) cm/s for LDH, and 0.01-0.03 x 10(-6) cm/s for alpha 2-macroglobulin.

Our aim was to determine the role of fetal breathing movements (FBM) in the maintenance of fetal lung liquid volume. Experiments were performed in 14 chronically catheterized fetal sheep. FBM were selectively abolished for 48 h by the infusion of tetrodotoxin (TTX) onto the phrenic nerves of five fetuses. Lung liquid volumes and secretion rates were measured before each treatment, 46–48 h after the start of the TTX infusion, and 22–24 h after the end of the infusion. Blockade of the phrenic nerves reduced fetal lung liquid volumes from 27.6 +/- 1.9 to 21.8 +/- 2.6 ml/kg and increased lung liquid secretion rates from 3.8 +/- 0.6 to 6.2 +/- 1.1 ml.h-1.kg-1. Control experiments confirmed the lack of effect of TTX infused intravenously and saline infused intrapleurally on changes in fetal lung liquid volume and secretion rate. To measure the static relaxation volume of the fetal lung, in six fetuses we combined skeletal muscle paralysis with bypass of the upper airway for 48 h. This reduced fetal lung liquid volume from 39.1 +/- 3.1 to 23.0 +/- 2.5 ml/kg and increased lung liquid secretion rates from 4.1 +/- 0.7 to 5.8 +/- 0.9 ml.h-1.kg-1. This experiment demonstrates that the fetal lung is normally maintained at a level of expansion that is much greater than its static relaxation volume. We conclude that the volume of luminal liquid in the fetal lungs is dependent on the diaphragmatic contractions associated with FBM. Their effect is to resist the elastic recoil of the fetal lungs, thereby reducing the loss of liquid from the lungs via the trachea.

The reliability of the esophageal balloon technique in measuring high-frequency changes in pleural pressure (Ppl) was investigated in six normal subjects by studying the amplitude ratio (A) and phase angle (phi) of esophageal (Pes) and mouth (Pm) pressures during airway occlusion and while pseudorandom pressure variations (2–32 Hz) were applied to the chest. The measurements were made with a common esophageal balloon-catheter system connected to a high-impedance piezoresistive transducer. When the cheeks were firmly supported, A averaged 1.08 +/- 0.063 at 2 Hz and 1.06 +/- 0.11 at 32 Hz. Pes increasingly led Pm with increasing frequency, and phi averaged 20.8 +/- 4.0 degrees at 32 Hz. Washing the airways with 80% He-20% O2 reduced phi by 50%. When the cheeks were not supported, A exhibited a strong positive frequency dependence, averaging 1.71 +/- 0.34 at 32 Hz, whereas phi increased much faster below 20 Hz and tended to decrease afterward. Because the esophageal transfer function Pes/Ppl = (Pes/Pm)/(Ppl/Pm), we could estimate Pes/Ppl by computing for individual subjects the pressure difference between the pleura and the mouth based on the lung and upper airway wall properties that were measured separately. The results suggest that the ratio of Pes and Ppl remains close to unity from 2 to 32 Hz, but Pes lags slightly behind Ppl (phi equals about -7 degrees at 32 Hz).

Postobstructive pulmonary vasculopathy, produced by chronic ligation of one pulmonary artery, markedly increases bronchial blood flow. Previously, using arterial and venous occlusion, we determined that bronchial collaterals enter the pulmonary circuit at the distal end of the arterial segment. In this study, we tested the hypothesis that pressure in bronchial collaterals (Pbr) closely approximates that at the downstream end of the arterial segment (Pao). We pump perfused [111 +/- 10 (SE) ml/min] left lower lobes of seven open-chest live dogs 3–15 mo after ligation of the left main pulmonary artery. Bronchial blood flow was 122 +/- 16 ml/min. We measured pulmonary arterial and venous pressures and, by arterial and venous occlusion, respectively, Pao and the pressure at the upstream end of the venous segment (Pvo). Pbr was obtained by micropuncture of 34 pleural surface bronchial vessels 201 +/- 16 microns in diameter. We found that Pbr (14.4 +/- 1.0 mmHg) was similar to Pao (15.0 +/- 0.8 mmHg) but differed significantly (P < 0.01) from Pvo (11.3 +/- 0.5 mmHg). In addition, Pbr was independent of systemic arterial pressure and bronchial vessel diameter. Light and electron microscopy revealed that, in the lobes with the ligated pulmonary artery, the new bronchial collaterals entered the thickened pleura from the parenchyma via either bronchovascular bundles or interlobular septa and had sparsely muscularized walls. We conclude that, in postobstructive pulmonary vasculopathy, bronchial collateral pressure measured by micropuncture is very close to the pressure in precapillary pulmonary arteries and that most of the pressure drop in the bronchial collaterals occurs in vessels > 350 microns in diameter.

Motivated by single lung transplantation, we studied the mechanics of the chest wall during single lung inflations in recumbent dogs and baboons and determined how pleural pressure (Ppl) is coupled between the hemithoraces. In one set of experiments, the distribution of Ppl was inferred from known volumes and elastic properties of each lung. In a second set of experiments, costal pleural liquid pressure (Pplcos) was measured with rib capsules. Both methods revealed that the increase in Ppl over the ipsilateral or inflated lung (delta Ppli) is greater than that over the contralateral or noninflated lung (delta Pplc). Mean d(delta Pplc)/d(delta Ppli) and its 95% confidence interval was 0.7 +/- 0.1 in dogs and 0.5 +/- 0.1 in baboons. In a third set of experiments in three dogs and three baboons, we prevented sternal displacement and exposed the abdominal diaphragm to atmospheric pressure during unilateral lung inflation. These interventions had no significant effect on Ppl coupling between the hemithoraces. We conclude that lungs of unequal size and mechanical properties need not be exposed to the same surface pressure, because thoracic midline structures and the lungs themselves resist displacement and deformation.

Six studies have been completed to reevaluate pleural surfactant as a possible boundary lubricant in mesothelial sliding. It is capable of remarkable antiwear action, giving a mean scar diameter on a standard “four-ball test” comparable to the best commercially available lubricants and reducing friction to values anticipated from lamellated solid lubricants such as graphite. Pleural surfaces displayed appreciable hydrophobicity, which was almost eliminated by rinsing with a lipid solvent from which phospholipid was recovered and quantified. These quantities indicated that equivalent of 7.3 adsorbed monolayers of surface-active phospholipid, which was in general agreement with the number of layers of a graphite-like surface coating visualized by electron microscopy by use of a novel fixation procedure that avoids conventional aldehydes known to destroy hydrophobic surfaces. Graphite-like (dry) lubrication by adsorbed surface-active phospholipid is discussed as an excellent lubrication system available wherever the distribution of fluid allows the pleura to make contact.

Positive pleural pressure (Ppl) decreases left ventricular afterload and preload. The resulting change in cardiac output (CO) in response to these altered loading conditions varies with the baseline level of cardiac contractility. In an isolated canine heart-lung preparation, we studied the effects of positive Ppl applied phasically during systole or diastole on CO and on the cardiac function curve (the relationship between CO and left atrial transmural pressure). When baseline cardiac contractility was enhanced by epinephrine infusion, systolic and diastolic positive Ppl decreased CO equally (1,931 +/- 131 to 1,419 +/- 124 and 1,970 +/- 139 to 1,468 +/- 139 ml/min, P less than 0.01) and decreased the pressure gradient driving venous return. However, neither shifted the position of the cardiac function curve, suggesting that the predominant effect of positive Ppl was decreased preload. When baseline cardiac contractility was depressed by severe respiratory acidosis, diastolic positive Ppl pulses caused no significant change in CO (418 +/- 66 to 386 +/- 52 ml/min), the cardiac function curve, or the pressure gradient for venous return. However, systolic positive Ppl pulses increased CO from 415 +/- 70 to 483 +/- 65 ml/min (P less than 0.01) and significantly shifted the cardiac function curve to the left. Thus the effect of Ppl pulsations on CO works through different mechanisms, depending on the state of cardiac contractility.

The morphology of the submesothelial lymphatic lacunae on the pleural and peritoneal surface over the tendinous and muscular portion of the diaphragm was studied in 10 anesthetized rabbits. The lymphatic network was evidenced by injecting 1 ml of colloidal carbon solution in the pleural (n = 5) or the peritoneal (n = 5) space. After 1 h of spontaneous breathing, the animal was killed and the diaphragm was fixed in situ by injection of approximately 5 ml of fixative in pleural and peritoneal spaces. Then both cavities were opened and the diaphragm was excised and pinned to a support. According to which cavity had received the injection, the peritoneal or the pleural side of the diaphragm was scanned by sequential imaging of the whole surface by use of a video camera connected to a stereomicroscope and to a video monitor. The anatomic design appeared as a network of lacunae running either parallel or perpendicular to the major axis of the tendinous or muscular fibers. The lacunae were more densely distributed on the tendinous peritoneal area than on the pleural one. Scanty lacunae were seen on the muscular regions of both diaphragmatic sides, characterized by large areas without lacunae. The average density of lacunae on tendinous and muscular regions was 6 and 1.7/cm2 for the pleural side and 25 and 3.4/cm2 for the peritoneal side, respectively. The average width of lacunae was 137.9 +/- 1.6 and 108.8 +/- 1.7 microns on the tendinous pleural and the peritoneal side, respectively, and 163 +/- 1.8 microns on the muscular portion of the pleural and peritoneal surfaces.

Our aim was to assess the mechanisms determining the reflex formation of an oral airway in response to nasal obstruction (NO) and tracheal obstruction (TO). In nine conscious lambs (14–37 days old) NO was effected by blockade of nasal tubes; TO was later effected by blockade of an endotracheal tube. We measured arterial O2 saturation, PO2, PCO2, and pH and the depth and duration of inspiratory efforts when mouth opening (MO) occurred. Responses were compared when NO and TO followed breathing of room air, rebreathed air, and 100% O2. After both NO and TO, MO was initiated most rapidly after lambs rebreathed air and least rapidly after they breathed 100% O2. Similar changes in blood gases and pH were measured when MO occurred after air breathing and rebreathing; however, the extent of these changes was greater during TO than during NO. After 100% O2 was breathed, MO occurred when lambs were still hyperoxic, but they were more hypercapnic and acidemic than after breathing air or rebreathed air. There were no differences, related to prebreathed gases or site of airway occlusion, in the depth of inspiratory efforts at the time of MO. We conclude that the formation of an oral airway requires a critical level of inspiratory drive in the presence of airway obstruction. After the prebreathing of different gases, differences in response latency and blood gases at the time of MO can be attributed to the attainment of this threshold level of inspiratory drive. The formation of an oral airway is facilitated by, but not dependent on, receptors in the upper airway.

The variation of pleural pressure was measured in anesthetized spontaneously breathing dogs subjected to increased acceleration (0–4 G) in a centrifuge. Two groups of animals were studied. In one group, the resultant acceleration was in a direction either ventral-to-dorsal (+Gx) or dorsal-to-ventral (-Gx), with a relatively small residual cranial-to-caudal acceleration. In the other group, the resultant acceleration was either cranial-to-caudal (+Gz) or caudal-to-cranial (-Gz), with a relatively small residual dorsal-to-ventral acceleration. Pleural liquid pressure (Ppl) was measured by two rib capsules that were separated by 7–9 cm and oriented either in the dorsal-to-ventral or cranial-to-caudal direction. At functional residual capacity, Ppl in the nondependent lung region became more negative when the acceleration was in the +Gx or +Gz direction. Thus the lung would be susceptible to damage that results from overexpansion in these acceleration directions. By contrast, acceleration in the -Gx or -Gz direction produced values of Ppl at functional residual capacity that were positive. Thus, in these acceleration directions, the respiratory muscles must provide greater force during inspiration to overcome lung compression before lung ventilation can occur. The Ppl gradients with respect to the acceleration directions increased approximately in proportion to acceleration in the +Gx, -Gx, and -Gz directions but remained relatively constant in the +Gz direction.

Abdominal distension (AD) occurs in pregnancy and is also commonly seen in patients with ascites from various causes. Because the abdomen forms part of the "chest wall," the purpose of this study was to clarify the effects of AD on ventilatory mechanics. Airway pressure, four (vertical) regional pleural pressures, and abdominal pressure were measured in five anesthetized, paralyzed, and ventilated upright pigs. The effects of AD on the lung and chest wall were studied by inflating a liquid-filled balloon placed in the abdominal cavity. Respiratory system, chest wall, and lung pressure-volume (PV) relationships were measured on deflation from total lung capacity to residual volume, as well as in the tidal breathing range, before and 15 min after abdominal pressure was raised. Increasing abdominal pressure from 3 to 15 cmH2O decreased total lung capacity and functional residual capacity by approximately 40% and shifted the respiratory system and chest wall PV curves downward and to the right. Much smaller downward shifts in lung deflation curves were seen, with no change in the transdiaphragmatic PV relationship. All regional pleural pressures increased (became less negative) and, in the dependent region, approached 0 cmH2O at functional residual capacity. Tidal compliances of the respiratory system, chest wall, and lung were decreased 43, 42, and 48%, respectively. AD markedly alters respiratory system mechanics primarily by "stiffening" the diaphragm/abdomen part of the chest wall and secondarily by restricting lung expansion, thus shifting the lung PV curve as seen after chest strapping. The less negative pleural pressures in the dependent lung regions suggest that nonuniformities of ventilation could also be accentuated and gas exchange impaired by AD.

The relationship between esophageal pressure and juxtacardiac pressures was studied during positive end-expiratory pressure (PEEP) ventilation applied to both lungs or selectively to one lung. The experiments were performed in eight anesthetized dogs with balloon catheters in the esophagus and in the left and right pericardial and overlying pleural cavities and with an open-ended liquid-filled catheter in the pleural cavity. Bilateral PEEP (10, 20, and 30 cmH2O) caused progressive and similar increments in left and right pleural pressure. Selective PEEP, however, increased ipsilateral pleural balloon pressure more than contralateral pressure. The increase in ipsilateral pleural balloon pressure markedly exceeded the increase in esophageal pressure. There was a small increase in pleural open-ended catheter pressure that approximated the increase in esophageal pressure. During selective PEEP, pericardial balloon pressure remained uniform because of a decrease in ipsilateral pericardial transmural pressure. In conclusion, selective PEEP caused nonuniform increments in regional pleural balloon pressure. Left and right pericardial balloon pressure, however, increased uniformly with selective PEEP because of reduced ipsilateral pericardial transmural pressure. The esophageal balloon did not reflect the marked regional increments in pleural balloon pressure with selective PEEP and consistently underestimated the changes in pleural balloon pressure with general PEEP.

To determine the effect of lung inflation and left atrial pressure on the hydrostatic pressure gradient for fluid flux across 20- to 60-microns-diam venules, we isolated and perfused the lungs from newborn rabbits, 7-14 days old. We used the micropuncture technique to measure venular pressures in some lungs and perivenular interstitial pressures in other lungs. For all lungs, we first measured venular or interstitial pressures at a constant airway pressure of 5 or 15 cmH2O with left atrial pressure greater than airway pressure (zone 3). For most lungs, we continued to measure venular or interstitial pressures as we lowered left atrial pressure below airway pressure (zone 2). Next, we inflated some lungs to whichever airway pressure had not been previously used, either 5 or 15 cmH2O, and repeated venular or interstitial pressures under one or both zonal conditions. We found that at constant blood flow a reduction of left atrial pressure below airway pressure always resulted in a reduction in venular pressure at both 5 and 15 cmH2O airway pressures. This suggests that the site of flow limitation in zone 2 was located upstream of venules. When left atrial pressure was constant relative to airway pressure, the transvascular gradient (venular-interstitial pressures) was greater at 15 cmH2O airway pressure than at 5 cmH2O airway pressure. These findings suggest that in newborn lungs edema formation would increase at high airway pressures only if left atrial pressure is elevated above airway pressure to maintain zone 3 conditions.

To determine whether lung edema leaks into the pleural space, we measured flow rates of visceral pleural liquid from exposed sheep lungs during volume loading and then compared the protein concentration of visceral pleural liquid and lung interstitial liquids (lymph and peribronchovascular cuff liquid). For 4 h, we volume loaded 24 anesthetized ventilated sheep with one side, both sides, or neither side of the chest open. During the experiment, we collected visceral pleural liquid from a bag surrounding the exposed lung and lung lymph; after the experiment, we collected peribronchovascular cuff liquid. We found that during volume loading visceral pleural liquid flow increased significantly by 2 h, and its protein concentration over the final hour was the same as that of lung interstitial liquids. The volume of visceral pleural liquid correlated with excess lung water and wedge pressure elevation. By our estimates, clearance of edema from the lung into the pleural space constituted 23-29% of all edema liquid collected, similar to measured lymph edema clearance. We conclude that edema liquid leaks directly from edematous sheep lungs into the pleural space and that this leakage provides an important additional route of edema clearance.

To assess the mechanisms of pulsus paradoxus (i.e., inspiratory decline of greater than or equal to 10 Torr in systolic pressure) in airway obstruction, we studied 12 patients with chronic airflow obstruction before and during breathing through an external resistance that provided loads during both inspiration and expiration. Esophageal pressure (Ppl) and brachial artery pressure, relative to either atmospheric (Pa) or esophageal pressure (Patm), were measured simultaneously during normal and loaded breathing. It was assumed that changes in intrathoracic systemic arterial transmural pressure were adequately represented by Patm. During control, no significant difference between systolic fluctuation (delta Pa) and pleural swings (delta Ppl) was found. Concurrently, inspiratory and expiratory Patm were nearly identical. By contrast, under maximally loaded conditions, higher magnitudes of delta Ppl than delta Pa were found and consequently Patm rose with inspiration. In this connection, the plot of delta Pa against delta Ppl showed that the slopes for delta Ppl less than or equal to 15 Torr (1.2 Torr delta Pa/delta Ppl) and delta Ppl greater than 15 Torr (0.4 Torr delta Pa/delta Ppl) were significantly different. Under all experimental conditions we found during inspiration a rise in diastolic Patm that is consistent with an increase in left ventricular afterload.(ABSTRACT TRUNCATED AT 250 WORDS)

Movements of the suprasternal fossa during spontaneous breathing monitored with the surface inductive plethysmograph (SIP) have been shown to reflect changes of intrapleural pressure in conscious humans. Calibration of this device in anesthetized intubated dogs was accomplished by adjusting the electrical gain of its analog waveform to be equivalent to changes of airway pressure during inspiratory efforts against an occluded airway. This procedure, denoted the occlusion test, was also used to identify the site of esophageal balloon catheter placement for its recording of intrapleural pressure deflections. The validity of SIP-derived estimates of inspiratory and expiratory pulmonary resistances and lung compliance was established by finding close agreement with measurements obtained with intraesophageal pressure changes during 1) unimpeded spontaneous breathing, 2) inspiratory resistive loading, 3) bronchoprovocation with aerosolized carbachol, 4) mechanical ventilatory modalities, and 5) induced pulmonary edema. Therefore, movements of the suprasternal fossa with respiration can be reliably transformed into quantitative or semiquantitative changes of intrapleural pressure in anesthetized intubated dogs during major alterations of pulmonary mechanics.

An intercostal retractometer was developed for estimation of intrapleural pressure changes in infants. It consists of a flat reference plate which floats over the interspace and is attached to the skin by a flexible plastic film. The pressure inside the device is measured with a strain gauge. The volume inside the device is adjusted, so that the intercostal space is brought to a condition of flatness and pressure changes in the device correlate linearly with intrapleural pressure changes. The retractometer is calibrated against overall intrapleural pressure changes by matching its output to changes in airway pressure during occlusion of the airway. The calibration factor is qualitatively proportional to the thickness of the subcutaneous tissue. Retractometer and intrapleural pressures were simultaneously measured in two infant rhesus monkeys with small pneumothoraces. Esophageal and retractometer pressures were compared in seven preterm infants with an average weight of 1345 g. The device estimated the monkeys' intrapleural pressure changes to within 1.2 cmH2O and the human preterm infants' esophageal pressure changes to within 1.3 cmH2O (95% confidence limits of a linear regression).

We have developed a minimally invasive method for measuring the hydrostatic pressure in the pleural space liquid. A liquid-filled capsule is bonded into a rib and a small hole is cut in the parietal pleura to allow direct communication between the liquid in the capsule and the pleural space. The pressure can be measured continuously by a strain gauge transducer connected to the capsule. The rib capsule does not distort the pleural space or require removal of intercostal muscle. Pneumothoraces are easily detected when they occur inadvertently on puncturing the parietal pleura. We examined the effect of height on pleural pressure in 15 anesthetized spontaneously breathing dogs. The vertical gradients in pleural pressure were 0.53, 0.42, 0.46, and 0.23 cmH2O/cm height for the head-up, head-down, supine, and prone body positions, respectively. These vertical gradients were much less than the hydrostatic value (1 cmH2O/cm), indicating that the pleural liquid is not in hydrostatic equilibrium. In most body positions the magnitudes of pleural liquid pressure interpolated to midchest level were similar to the mean transpulmonary (surface) pressure determined postmortem. This suggests that pleural liquid pressure is closely related to the lung static recoil.

Pressure-volume characteristics of the lung have been thought to be due primarily to the properties of the network of alveolar septa. However, Hajji et al. (J. Appl. Physiol.: Respirat . Environ. Exercise Physiol. 47: 175–181, 1979) attributed a substantial role to the visceral pleura. Seeking a structural explanation for this result, we compared the relative amounts of collagen fibrils and elastin fibers in the visceral pleura and alveolar parenchyma using stereological measurements in five canine lobes. We found about one-fifth as much collagen and one-tenth as much elastin in the pleura as in the alveolar parenchyma. This structural result confirms the functional conclusions of Hajji et al. We argue that such a substantial structure is not needed for protection against overinflation but may have to do with stabilization of lobe shape or handling of frictional forces.

To study respiratory muscle interaction in patients with occlusive apnea, diaphragmatic electromyogram (EMGdi) and gastric, pleural, and transdiaphragmatic pressures (Pga, Ppl, and Pdi, respectively) were studied in seven patients during non-rapid-eye-movement (NREM) sleep. Diaphragmatic force output, as assessed by Pdi, followed the periodic changes in EMGdi but during the occlusive phase the increase in Pdi was more than the increase in EMGdi. This increase in Pdi was essentially due to an increase in Ppl, since Pga and EMGdi had a linear relationship (r = 0.98, P less than 0.001) that did not change during the occlusive and ventilatory phases. Abdominal muscle recruitment evident in Pga and abdominal motion tracings during the occlusive phase when paradoxical rib cage motion was observed suggested that this increase in diaphragmatic efficiency was likely due to a change in diaphragmatic length-tension characteristics. These results demonstrate that, in patients with occlusive apneas, the diaphragm is the predominant respiratory muscle during NREM sleep and that its function is supported by abdominal muscle recruitment.

The influence of alterations in hydrostatic and oncotic pressure gradients on fluid movement across the visceral pleura was examined in 16 spontaneously breathing anesthetized dogs. The left lung was enclosed in a water-impermeable polyethylene membrane, creating a visceral pleural space; visceral fluid movement was determined as the formation or reabsorption of fluid in this space. Aortic, pulmonary arterial, right and left atrial, and pleural pressures were monitored; oncotic pressure was calculated from the protein concentration of plasma and pleural fluid. Left atrial pressure was varied from 0 to 30 mmHg and pulmonary arterial pressure from 15 to 36 mmHg by inflating atrial balloon catheters; the plasma-to-pleural fluid oncotic gradient was varied from 6.8 to 19.3 mmHg by infusing saline. The movement of fluid across the visceral pleura was significantly (P less than 0.001) related to the effective (transmural hydrostatic pressure minus oncotic gradient) pulmonary arterial (r = 0.87) and left atrial pressures (r = 0.92). The filtration coefficient of the visceral pleura estimated by our technique was 1.1 x 10(-6) ml.s-1.cmH2O-1.cm-2. These results not only confirm the concept that fluid flux across the visceral pleura is determined by the action of Starling forces across this membrane but also provide an estimate of the filtration coefficient for the visceral pleura.

When an excised lung lobe undergoes atelectasis, its shape differs from that observed when lobar atelectasis occurs in an intact animal: the chest wall deforms the collapsing lobe. In eight anesthetized dogs in the left lateral position we measured lung volume and transpulmonary pressure during the development of atelectasis. We then induced atelectasis of the left lower lobe with the rest of the lung maintained at FRC and measured lobar volume and "translobar" (lobar minus esophageal) pressure. Lung and lobar volumes were measured by prebreathing the animal with 88% O2-12% N2, occluding the airway and observing the increase in lung or lobar N2 concentration. When the left lower lobe alone collapsed, translobar pressures were more negative than transpulmonary pressure at the same relative volume when the whole lung collapsed. This pressure difference, which represents the deforming force applied to the lobe minus the pressure costs of deformation, averaged 3 cmH2O at 50% FRC. Infusion of 25 ml of normal saline into the pleural space sharply reduced the difference pulmonary pressure during lung collapse: this difference was abolished at 80% FRC and halved at 50% FRC. The large effect of the small volume of fluid suggested that deforming forces were largely generated in relatively local areas, such as regions of the chest wall with sharp angulation.

Pleural liquid pressure was measured at end expiration in 11 spontaneously breathing anesthetized ponies in the prone and supine positions. A liquid-filled capsule was implanted into a rib to measure pleural liquid pressure with minimal distortion of the pleural space (Wiener-Kronish et al., J. Appl. Physiol. 59: 597-602, 1985). Capsule position relative to lung height was measured from thoracic radiographs taken in each position. In each body position, pleural liquid pressure was most negative in the superior lung regions and least negative in the inferior lung regions. In the supine position, the magnitude of the vertical gradient in pleural liquid pressure was 0.67 cmH2O/cm ht and was not significantly different from 1 cmH2O/cm ht. In the inferior lung regions (less than 50% lung ht), pleural liquid pressure averaged -1.3 cmH2O, indicating a low transpulmonary pressure over the region of the chest where most of the lung mass is located. When animals were in the prone position, the magnitude of the vertical gradient in pleural liquid pressure was 0.14 cmH2O/cm ht and was not statistically different from 0 cmH2O/cm ht. In each body position, mean transpulmonary pressure, measured postmortem, was similar to the estimated magnitude of pleural liquid pressure at 50% lung ht. This suggests that pleural liquid pressure is closely related to pleural surface pressure. These results are consistent with the poor ventilation distribution and reduced lung volumes measured in anesthetized horses in the supine position compared with values measured in horses in the prone position.

Regional lung ventilation is modulated by the spatiotemporal distribution of alveolar distending forces. During positive-pressure ventilation, regional transmission of airway pressure (Paw) to the pleural surface may vary with ventilatory frequency (f), thus changing interregional airflow distribution. Pendelluft phenomena may result owing to selective regional hyperventilation or phase differences in alveolar distension. To define the effects of f on regional alveolar distension during positive-pressure ventilation, we compared regional pleural pressure (Ppl) swings from expiration to inspiration (delta Ppl) and end-expiratory Ppl over the f range 0-150 min-1 in anesthetized, paralyzed, close-chested dogs with normal lungs. We inserted six pleural balloon catheters to analyze Ppl distribution along three orthogonal axes of the right hemithorax. Increases in regional Ppl were synchronously coupled with inspiratory increases in Paw regardless of f. However, at a constant tidal volume and percent inspiratory time, end-expiratory Paw and Ppl increased in all regions once a f threshold was reached (P less than 0.01). Supradiaphragmatic delta Ppl were less than in other regions (P less than 0.05), but thoracoabdominal binding abolished this difference by decreasing thoracoabdominal compliance. We conclude that the distribution of forces determining dynamic regional alveolar distension are temporally synchronous but spatially asymmetric during positive-pressure ventilation at f less than or equal to 150/min.

We measured the changes in pleural surface pressure (delta Ppl) in the area of apposition of the rib cage to the diaphragm (Aap) in anesthetized dogs during spontaneous breathing, inspiratory efforts after airway occlusion at functional residual capacity, and phrenic stimulation. Intact dogs were in supine or lateral posture; partially eviscerated dogs were in lateral posture. delta Ppl,ap often differed significantly from changes in abdominal pressure (delta Pab); sometimes they differed in sign (except during phrenic stimulation). Changes in transdiaphragmatic pressure in Aap (delta Pdi,ap) could be positive or negative and were less in eviscerated than in intact dogs. delta Pdi,ap could differ in sign among respiratory maneuvers and over different parts of Aap. Hence average delta Pdi,ap should be closer to zero than delta Pdi,ap at a given site. Since delta Ppl,ap = delta Prc,ap, where Prc,ap represents rib cage pressure in Aap, delta Pdi,ap = delta Pab - delta Prc,ap. Hence, considering that delta Pab and delta Prc depend on different factors, delta Pdi,ap may differ from zero. This pressure difference seems related to the interaction between two semisolid structures (contracted diaphragm and rib cage in Aap) constrained to the same shape and position.

Several manifestations of lung disease during infancy suggest that mechanical interdependence can be relatively high in newborn lungs. To test this possibility, we measured elastic moduli and pleural membrane tension in lungs excised from piglets ranging in age from less than 12 h to 85 days. Near maximum inflation, newborn lungs (less than 12 h, n = 6) had no detectable pleural membrane tension, although 3- to 5-day-old lungs (n = 6) had tension greater than 5,000 dyn/cm. In contrast, parenchymal recoil was greater in the newborn lungs [19.3 +/- 3.0 (SD) vs. 14.3 +/- 2.4 cmH2O at 90% of maximum inflation volume, P less than 0.01]. Shear moduli were higher (13.5 +/- 4.6 vs. 9.2 +/- 1.5 cmH2O at 15 cmH2O transpulmonary pressure, P less than 0.05) and Poisson ratios were lower in the newborn lungs as compared with the 3- to 5-day-old lungs. Postnatal lung growth between 3 and 85 days was characterized by 1) a constant shear modulus (0.6 times transpulmonary pressure); 2) decrease in the bulk modulus (from 6.8 to 5.1 times transpulmonary pressure, P less than 0.005); and 3) evidence of gas trapping at progressively higher transpulmonary pressures. Therefore, growth of parenchyma in the piglet lung is associated with reduced stiffness to volume change but with no effect on overall stiffness to shape change. Nevertheless, a relatively great stiffness to shape change occurs transiently in newborn piglet lungs.

The indirect measurement of pleural pressure in neonates is obtained from measurements of esophageal pressure (Pes) with either a liquid-filled catheter or an esophageal balloon-catheter system. The purpose of this investigation was to assess the validity of the water-filled esophageal catheter by comparing the simultaneous changes in Pes and airway opening pressure (Pao) during occluded respiratory efforts. Equal changes in Pes and Pao under this condition indicate that Pes is a valid measurement of pleural pressure. In six healthy unsedated term neonates (aged 2–3 days) we measured Pes in the lower third of the esophagus with a water-filled catheter of eight French gage (FC), which has a 2-mm internal diameter. During occlusions, changes in Pes and Pao were almost identical in magnitude and timing in each body position studied (right lateral, prone, and supine). We conclude that the water-filled 8-FG esophageal catheter gives an accurate measurement of pleural pressure changes in healthy neonates.

We applied high-frequency oscillatory ventilation (HFOV) of low amplitude to the pleural surface of the isolated rat lung (IPL) perfused at 10 ml X min-1 with Krebs bicarbonate containing 4.5% albumin (hematocrit 34%). Lung volume was held constant by a continuous positive airways pressure (CPAP) of 5 cmH2O. Varying CPAP from 2 to 15 cmH2O did not affect O2 uptake. Tidal volume (VT) was estimated with an impedance pneumograph, and it bore a direct linear relationship to the amplitude of both the loudspeaker input signal and the pressure change in the chamber up to 30 Hz; VT was inversely proportional to the frequency (f). However, at a constant loudspeaker input of 10 V, minute expired ventilation (VE) remained constant (mean 104 ml X min-1) as f increased from 5 to 30 Hz. Hemoglobin saturation increased by more than 80% during HFOV of 5–30 Hz and amplitude of 10 V, the maximum O2 uptake being 14.6 ml O2 per 100 ml perfusate. Whereas dead space was approximately 335 microliters, a VT of less than 40 microliters could effect normal O2 uptake, suggesting that bulk flow is playing only a minor role in gas exchange. HFOV for 60 min (CPAP 5 cmH2O) did not affect the amount of alveolar surfactant compared with conventional ventilation at the same mean airway pressure. We conclude that normal O2 uptake can be maintained by applying HFOV to the pleural surface of the IPL held at constant volume.

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.

If the pulmonary lymphatics and/or interstitium of the lung participate in visceral pleural (VP) fluid exchange, then increasing the water content of the interstitial compartment by lymphatic ligation (L) should increase the filtration and/or decrease the absorption of fluid across the VP membrane. To test this hypothesis, the hydraulic conductivity (Lp) and diffusional permeability for protein (Pd) of the visceral pleura were determined in eight spontaneously breathing anesthetized chronic L dogs and seven sham-operated (S) controls. The left lung was enclosed in a water-impermeable membrane, creating a VP space; fluid flux was determined as the filtration or reabsorption of water and protein in the VP space. Intravascular and pleural pressures and the protein concentration of plasma and pleural fluid were monitored during two or more experimental periods in which different mixtures of plasma and saline were introduced in the VP space. At similar pulmonary capillary pressures, the extravascular lung water of the L animals [5.36 (+/- 0.32) g/g dry blood-free lung] was significantly (P less than 0.001) greater than that of the S dogs [3.79 (+/- 0.13)]. The Lp of the L dogs [6.8 (+/- 1.6) X 10(-7) ml X s-1 X cm-2 X Torr-1] was virtually identical (P greater than 0.8) to the 6.7 (+/- 1.4) ml X s-1 X cm-2 X Torr-1 of the S controls. Similarly, Pd in the L group [4.3 (+/- 0.5) X 10(-6) cm/s] was similar (P greater than 0.5) to that of the S animals [5.1 (+/- 1.1) X 10(-6) cm/s]. We conclude that neither the pulmonary lymphatics nor the interstitium of the lung contribute to VP fluid exchange.

We determined a rate of protein egress from the pleural cavity into thoracic duct lymph in seven anesthetized sheep in whom we had made 10-ml/kg hydrothoraces containing 1% plasma protein labeled with 125I-albumin. The labeled protein left the pleural space at an average rate of 0.02 ml X kg-1 X h-1. In 25 unanesthetized sheep we injected labeled protein intravenously and collected pleural fluid and plasma at intervals up to 48 h. The radioactivity in the sheeps' plasma fell twice as rapidly as the rate observed in humans. The half time for equilibration between plasma and pleural fluid protein specific activity was approximately 6 h. In seven sheep we gave a continuous infusion of tracer protein. In six of these seven sheep we collected superficial cervical lymph. The protein concentration in the lymph was three times that of pleural fluid. The half time for protein specific activity equilibration between plasma and pleural fluid was 5 h and 3–4 h between plasma and superficial cervical lymph. The rate of protein turnover in the pleural space appears to be much slower than previously reported.

We studied cardiopulmonary interdependence in ten pentobarbital sodium-anesthetized dogs by 1) measuring the increase of left atrial pressure (Pla) required to hold cardiac output (Q) constant on application of a positive end-expiratory pressure (PEEP), 2) determining the reduction of Pla required to mimic the Q fall observed when PEEP was applied while Pla was held constant, and 3) comparing left ventricular pressure-volume curves measured in freshly dead dogs during ventilation with and without PEEP. The atrial pressure changes can be divided into terms for pleural pressure change, lung deformation, and an undefined residual component and can be used to obtain a compliance opposing ventricular filling. Another compliance was derived from the pressure-volume curves. The latter compliance (6.8 ml/cm H2O) significantly exceeded the former (3.9 ml/cm H2O). The difference may have been caused by ventricular interdependence. The respiratory system compliance opposing ventricular filling was approximately one-twentieth of that predicted from lung and chest wall compliances. Deformation of lungs and chest wall appears to be a significant component of the elastic load imposed on ventricular diastolic filling.