Pleural liquid pressure in dogs measured using a rib capsule

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.     

Permeability-surface area product and reflection coefficient of the parietal pleura in dogs.

The parameters describing the permeability of the parietal pleura to liquid and total plasma proteins were measured in five anesthetized adult dogs. Small areas of parietal pleura (approximately 1 cm2) and the underlying endothoracic fascia were exposed through resection of the skin and the intercostal muscles. The portion of the thorax containing the pleural windows was removed from the chest and fixed over a bath of whole autologous plasma, the inner parietal pleural surface facing the bath. Small hemispheric Perspex capsules (surface area 0.28 cm2) connected to a pressure manometer were glued to the pleural windows; a subatmospheric pressure was set into the capsule chamber to create step hydraulic transpleural pressure gradients (delta P) ranging from 5 to 60 cmH2O. Transpleural liquid flows (Jv) and protein concentration of the capsular filtrate (Cfilt) and of the plasma bath were measured at each delta P. The transpleural protein flux (Js) at each delta P was calculated by multiplying Jv by the corresponding Cfilt. The hydraulic conductivity (Lp) of the parietal pleura was obtained from the slope of the Jv vs. delta P linear regression. The average Lp from 14 capsules was 9.06 +/- 4.06 (SD) microliters.h-1.cmH2O-1.cm-2. The mathematical treatment of the Js vs. Jv relationship allowed calculation of the unique Peclet number at the maximal diffusional protein flux and a corresponding osmotic permeability coefficient for plasma protein of 1 x 10(-5) +/- 0.97 x 10(-5) cm/s. The reflection coefficient calculated from the slope of the linear phase of the Js vs. Jv relationship was 0.11 +/- 0.05.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pleural and extrapleural interstitial liquid pressure measured by cannulas and micropipettes

In 15 anesthetized apneic, oxygenated rabbits we simultaneously measured pleural liquid and interstitial extrapleural parietal pressures by using catheters and/or cannulas and micropipettes connected to a servonull system. With the animal in lateral posture, at an average recording height of 4.4 +/- 0.9 (SD) cm from the most dependent part of the cavity, the extrapleural catheter and the pleural cannula yielded -2.5 +/- 0.6 and -5.5 +/- 0.2 cmH2O; the corresponding values for micropipette readings in the two compartments were -2.4 +/- 0.6 and -5.4 +/- 0.4 cmH2O, respectively (not significantly different from those measured with catheters and cannulas). In the supine animal, interstitial extrapleural catheter pressure data obtained at recording heights ranging from 15 to 80% of pleural cavity lay on the identity line when plotted vs. the micropipette pressure values simultaneously gathered from the same tissues. We conclude that 1) micropipettes and catheters-cannulas yield similar results when recording from the same compartment and 2) the hydraulic pressure in the parietal extrapleural interstitium is less negative than that in the pleural space.     

Transdiaphragmatic transport of tracer albumin from peritoneal to pleural liquid measured in rats.

In conscious Wistar-Kyoto rats, we studied the uptake of radioactive tracer (125)I-albumin into the pleural space and circulation after intraperitoneal (IP) injections with 1 or 5 ml of Ringer solution (3 g/dl albumin). Postmortem, we sampled pleural liquid, peritoneal liquid, and blood plasma 2-48 h after IP injection and measured their radioactivity and protein concentration. Tracer concentration was greater in pleural liquid than in plasma approximately 3 h after injection with both IP injection volumes. This behavior indicated transport of tracer through the diaphragm into the pleural space. A dynamic analysis of the tracer uptake with 5-ml IP injections showed that at least 50% of the total pleural flow was via the diaphragm. A similar estimate was derived from an analysis of total protein concentrations. Both estimates were based on restricted pleural capillary filtration and unrestricted transdiaphragmatic transport. The 5-ml IP injections did not change plasma protein concentration but increased pleural and peritoneal protein concentrations from control values by 22 and 30%, respectively. These changes were consistent with a small (approximately 8%) increase in capillary filtration and a small (approximately 20%) reduction in transdiaphragmatic flow from control values, consistent with the small (3%) decrease in hydration measured in diaphragm muscle. Thus the pleural uptake of tracer via the diaphragm with the IP injections occurred by the near-normal transport of liquid and protein.     

Size-related differences in parietal extrapleural and pleural liquid pressure distribution

The hydraulic pressure in the extrapleural parietal interstitium (Pepl) and in the pleural space over the costal side (Pliq) was measured in anesthetized spontaneously breathing supine adult mammals of increasing size (rats, dogs, and sheep) using saline-filled catheters and cannulas, respectively. From the Pliq and Pepl vs. lung height regressions it appears that in all species Pliq was significantly more subatmospheric than Pepl simultaneously measured at the same lung height. The vertical pleural liquid pressure gradient increased with size, amounting to -1, -0.69, and -0.44 cmH2O/cm in rats, dogs, and sheep, respectively. The vertical extrapleural liquid pressure gradient also increased with size, being -0.6, -0.52, and -0.33 cmH2O/cm in rats, dogs, and sheep, respectively. With increasing body size, the transpleural hydraulic pressure gradient (Ptp = Pepl - Pliq) at the level of the right atrium increased from 1.45 to 5.6 cmH2O going from rats to sheep. In all species Ptp increased, with lung height being greatest in the less dependent part of the pleural space.     

Distribution of diaphragmatic lymphatic lacunae.

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.     

Liquid thickness vs. vertical pressure gradient in a model of the pleural space

In recent studies using relatively noninvasive techniques, the vertical gradient in pleural liquid pressure was 0.2-0.5 cmH2O/cm ht, depending on body position, and pleural liquid pressure closely approximated lung recoil (J. Appl. Physiol. 59: 597-602, 1985). We built a model to discover why the vertical gradient in pleural pressure is less than hydrostatic (1 cmH2O/cm). A long rubber balloon of cylindrical shape was inflated in a plastic cylinder. The "pleural" space between the balloon and cylinder was filled with blue-dyed water. With the cylinder vertical, we measured pleural pressure by a transducer through side taps at 2-cm intervals up the cylinder. The pressure was measured with different amounts of water in the pleural space. With a clear separation between the balloon and the container, the vertical gradient in pleural liquid pressure was hydrostatic. As water was withdrawn from the pleural space, the balloon approached the wall of the container. Over an 8-cm-long midregion of the model where the balloon diameter matched the cylinder diameter, the vertical gradient was not hydrostatic and was virtually absent. In this region, the pleural liquid pressure was uniform and equal to the recoil of the balloon. In this section we could not see any pleural space. By scintillation imaging using 99mTc-diethylenetriamine pentaacetic acid in the water, we estimated the thickness of this flat "costal" pleural space to be approximately 20 microns. Radioactive tracer injected at the top of the pleural space appeared by 24 h at the bottom, which indicated a slow drainage of liquid by gravity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intrapleural liquid flow down a gravity-dependent hydraulic pressure gradient

We studied the vertical movement of 2 mg technetium-labeled albumin injected intrapleurally in 0.5 ml saline (15% of pleural liquid volume) in eight spontaneously breathing anesthetized dogs subject to a sudden change in posture (prone to supine or vice versa). The albumin movements were evaluated through a large field gamma camera placed laterally to the animal and detecting total (AT) and regional activities from two superimposed equal areas (At and Ab, top and bottom, respectively). The At/Ab ratio decreased from 2.1 to 1.3 in four animals up to 20 min from the change in posture and from 0.9 to 0.5 in four more animals studied from 50 to 90 min from turning maneuver. The rate of change in At and Ab was similar in the two groups of animals and unaffected by the acquisition posture. AT decreased by 7.7 and 3.5% for the two groups, respectively, reflecting albumin clearance from the pleural space. The opposite time course of regional activities and the independence of their rate of change of the At/Ab ratio and of the animal posture suggest a top-to-bottom albumin transfer occurring through a bulk flow of liquid estimated at 0.006 ml.kg-1.h-1. The data are consistent with a measured vertical pleural liquid pressure gradient that does not reflect a hydrostatic condition.     

Pleural space thickness in situ by light microscopy in five mammalian species

The thickness of the pleural space was measured by a focusing method using a light microscope (X157, 2.5-micron depth of focus). In anesthetized animals, thin transparent parietal pleural windows were made by dissection of intercostal muscle. Multiple postmortem measurements were made of the combined thickness of the pleural space and the window by focusing in sequence on the lung surface and on 1- to 2-micron tantulum particles sprayed on the window. The window thickness was measured after creating a pneumothorax and retracting the lungs. In supine rabbits the pleural space measured at various heights on the costal surface was of uniform thickness (16 micron) except for a thicker region (62 micron) located within 3 mm of the most dependent part of the lung. The thicker region reverted to the uniform thickness after it was placed in a nondependent position by inverting the animal from the supine to prone position, indicating fluid drainage by gravity. In the prone position near midchest, pleural space thickness (t) averaged 6.9 micron in the mouse, 10.2 in the rat, 17.2 in the rabbit, 18.3 in the cat, and 23.6 in the dog. Animals of larger body mass (M, kg) had a wider pleural space: t = 13.1 X M0.20. There was no contact between the two pleurae, indicating that fluid lubrication facilitates sliding between the lung and chest wall. Based on the t vs. M relationship and estimates of the viscous flow of pleural liquid, pleural fluid exchange rate would be proportional to body mass and the work of sliding as a fraction of the work of breathing would be smaller in larger animals.     

Respiratory syncytial virus infection in anesthetized weanling rather than adult rats prolongs the apneic responses to right atrial injection of capsaicin.

Apnea is a common complication in infants infected by respiratory syncytial virus (RSV). A recent study has shown that intranasal inoculation of RSV in conscious weanling rats strengthens the apneic responses to right atrial injection of capsaicin (CAP), leading to 66% mortality. The objectives of the present study were to determine 1) whether RSV infection changes baseline minute ventilation (Ve) and arterial blood gases in anesthetized rats; 2) what the effects of RSV infection are on the respiratory responses to CAP; and 3) whether the RSV-strengthened apneic responses are age dependent. Our experiments were conducted in anesthetized and spontaneously breathing rats divided into four groups of weanling and adult rats that received either intranasal inoculation of RSV or virus-free medium. Two days after RSV infection (0.7 ml/kg), animal blood gases, baseline Ve, and Ve responses to right atrial injection of three doses of CAP (4, 16, and 64 microg/kg) were measured and compared among the four groups. Our results showed that RSV infection increased respiratory frequency (approximately 25%, P<0.05) in weanling but not adult rats, with little effect on arterial blood gases. RSV infection amplified the apneic responses to CAP in weanling but not adult rats, characterized by increases in the initial (40%) and the longest apneic duration (650%), the number of apneic episodes (139%), and the total duration of apneas (60%). These amplifications led to 50% mortality (P<0.05). We conclude that RSV infection increases respiratory frequency and strengthens the apneic responses to CAP only in anesthetized weanling but not adult rats.     

No evidence for mesothelial cell contact across the costal pleural space of sheep

Pleural space width was measured by four morphological approaches using either frozen hydrated or freeze-substituted blocks of chest wall and lung. Anesthetized sheep were held in the lateral (n = 2), sternal recumbent (n = 2), or vertical (head-up; n = 2) position for 30 min. The ribs and intercostal muscles were excised along a 20-cm vertical distance of the chest wall region, which was sprayed with liquid Freon 22, cooled with liquid nitrogen, to facilitate the fastest possible freezing of the visceral and parietal pleura. We measured pleural space width in frozen hydrated blocks by reflected-light and low-temperature scanning electron microscopy and in freeze-substituted, fixed, and embedded tissue blocks by light and transmission electron microscopy. We combined the data from the two groups of sheep held sternally recumbent and vertical because the results were comparable. The average arithmetic mean data for pleural space width determined by reflected-light analysis for samples near the top (18.5 microns) and bottom (20.3 microns) of the chest, separated by 15 cm of lung height, varied inversely with lung height (n = 4; P less than 0.009). The average harmonic mean data demonstrated a similar gravity-dependent gradient (17.3 and 18.8 microns, respectively; P less than 0.02). Therefore a slight vertical gradient of approximately -0.10 micron/cm of lung height was found for costal pleural space width. Pleural space width in the most dependent recesses, such as the costodiaphragmatic recess, reached 1-2 mm. We never found any contacts between the visceral and parietal pleura with either of the frozen hydrated preparations. No points of mesothelial cell contact were revealed in the light- and transmission electron microscopic views of the freeze-substituted tissue, despite an apparent narrower pleural space associated with the tissue-processing steps. We conclude that the pleural space has a slightly nonuniform width, contacts if they occur must be very infrequent, and pleural liquid clearance is probably facilitated by liquid accumulation in dependent regions where lymphatic pathways exist.     

Hydrodynamic thickening of lubricating fluid layer beneath sliding mesothelial tissues

The delicate mesothelial surfaces of the pleural space and other serosal cavities slide relative to each, lubricated by pleural fluid. In the absence of breathing motion, differences between lung and chest wall shape could eventually cause the lungs and chest wall to come into contact. Whether sliding motion keeps lungs and chest wall separated by a continuous liquid layer is not known. To explore the effects of hydrodynamic pressures generated by mesothelial sliding, we measured the thickness of the liquid layer beneath the peritoneal surface of a 3-cm disk of rat abdominal wall under a normal stress of 2 cm H2O sliding against a glass plate rotating at 0-1 rev/s. Thickness of the lubricating layer was determined microscopically from the appearance of fluorescent microspheres adherent to the tissue and glass. Usually, fluid thickness near the center of the tissue disk increased with the onset of glass rotation, increasing to 50-200 microm at higher rotation rates, suggesting hydrodynamic pumping. However, thickness changes often differed substantially among tissue samples and between clockwise and counter-clockwise rotation, and sometimes thickness decreased with rotation, suggesting that topographic features of the tissue are important in determining global hydrodynamic effects. We conclude that mesothelial sliding induces local hydrodynamic pressure gradients and global hydrodynamic pumping that typically increases the thickness of the lubricating fluid layer, moving fluid against the global pressure gradient. A similar phenomenon could maintain fluid continuity in the pleural space, reducing frictional force and shear stress during breathing.     

Liquid and protein dynamics using a new minimally invasive pleural catheter in rabbits.

To obtain continuous access to the pleural space without causing injury, we tested a new transdiaphragmatic pleural catheter for its ability 1) to drain the pleural space without injury and 2) to drain liquid at a rate equal to normal pleural liquid production. In 13 anesthetized rabbits, we opened the abdomen and dissected through the diaphragm to insert a flared-tip catheter into the ventral pleural space on one side and then turned the rabbit prone. In 10 of the rabbits (8 for 6 h, 2 for 24 h), we continuously collected draining pleural liquid, and in 3 rabbits (6 h), we did not open the catheter. We injected radiolabeled albumin intravenously as a protein marker. Terminally, we collected pleural liquid from both pleural spaces and lavaged for total radioactivity. In 14 awake control rabbits without catheters, we measured normal pleural liquid production by the rate of equilibration of radiolabeled albumin from plasma to pleural liquid. We found that, although the percentage of neutrophils was increased on the side with the catheter (54 vs. 1% in control rabbits), the pleural liquid volume, protein concentration, specific activity of albumin, and total radioactivity in the pleural space were the same on the side with the catheter as on the opposite side and in the control rabbits. The liquid flow rate through the catheter over 6 h was 53 +/- 23 microliters/h [0.017 +/- 0.008 (SD) ml.kg-1.h-1], which was not significantly different from the computed rate of normal pleural liquid production in the control rabbits, 49 +/- 14 microliters/h (0.016 +/- 0.004 ml.kg-1.h-1).(ABSTRACT TRUNCATED AT 250 WORDS)     

Pleural stress pressure as a force to control liquid accumulation and maintain lung expansion

Total gas pressure in the pleural space is more subatmospheric than that in the alveolar cavity. This pressure difference minus elastic recoil pressure of the lung was termed stress pressure. We investigated the relationship between stress pressure and a force that would hold the lung against the chest wall to prevent accumulation of liquid. The condition was a pleural space with an enlarged pleural surface pressure. Dogs anesthetized with pentobarbital sodium were placed in a box maintained subatmospherically at approximately -30 cmH2O and breathed atmospheric air for 4 h. Liquid volume in the pleural space of the dogs was measured under conditions of thoracotomy. In the normal group, the volume of the pleural liquid was within the normal range of approximately 2.0 ml and the visceral and the parietal pleura made contact. In the pneumothorax group, established by injecting 50 ml of air into the pleural space, the liquid increased significantly in all cases by a mean value of approximately 12 ml. Thus pleural stress pressure seems to be an important force holding the lung against the chest wall and aiding in the control of accumulation of liquid in a more subatmospheric pleural space.     

Role of adenosine in hypoxic ventilatory depression

The role of adenosine in the ventilatory depression induced by hypoxia was studied in 82 spontaneously breathing urethan-anesthetized 4-day-old rabbit pups. Respiration was monitored with a pneumotachograph. The animals were exposed to hypoxia (6% O2 in N2) for 30 min or until the occurrence of terminal apnea. In all animals hypoxia produced an initial increase in ventilation followed by a decrease. In the control group 52% of the animals became apneic after 7 min of hypoxic exposure. By contrast, pretreatment with dipyridamole (10 or 20 mg/kg), an adenosine uptake blocker, significantly shortened the time needed to reach apnea. Thus at 7 min of hypoxia 93% of the animals that received dipyridamole became apneic. On the other hand, administration of adenosine antagonists 8-p-sulfophenyltheophylline (5 or 8 mg/kg) and aminophylline (10 or 25 mg/kg) significantly prolonged the time required to produce apnea. Only 20% of the animals that received these antagonists became apneic at 7 min of hypoxia. These results suggest that adenosine is potentially involved in the ventilatory depression produced by hypoxia in neonatal rabbit pups.     

Regional variations in lung expansion in rabbits: prone vs. supine positions

We studied the vertical gradient in lung expansion in rabbits in the prone and supine body positions. Postmortem, we used videomicroscopy to measure the size of surface alveoli through transparent parietal pleural windows at dependent and nondependent sites separated in height by 2-3 cm at functional residual capacity (FRC). We compared the alveolar size measured in situ with that measured in the isolated lungs at different deflationary transpulmonary pressures to obtain transpulmonary pressure (pleural surface pressure) in situ. The vertical gradient in transpulmonary pressure averaged 0.48 +/- 0.16 (SD) cmH2O/cm height (n = 10) in the supine position and 0.022 +/- 0.014 (SD) cmH2O/cm (n = 5) in the prone position. In mechanically ventilated rabbits, we used the rib capsule technique to measure pleural liquid pressure at different heights of the chest in prone and supine positions. At FRC, the vertical gradient in pleural liquid pressure averaged 0.63 cmH2O/cm in the supine position and 0.091 cmH2O/cm in the prone position. The vertical gradients in pleural liquid pressure were all less than the hydrostatic value (1 cmH2O/cm), which indicates that pleural liquid is not generally in hydrostatic equilibrium. Both pleural surface pressure and pleural liquid pressure measurements show a greater vertical gradient in the supine than in the prone position. This suggests a close relationship between pleural surface pressure and pleural liquid pressure. Previous results in the dog and pony showed relatively high vertical gradients in the supine position and relatively small gradients in the prone position. This behavior is similar to the present results in rabbits. Thus the vertical gradient is independent of animal size and might be related to chest shape and weight of heart and abdominal contents.     

Measurement of the CO2 apneic threshold in newborn infants: possible relevance for periodic breathing and apnea.

We measured the PCO2 apneic threshold in preterm and term infants. We hypothesized that, compared with adult subjects, the PCO2 apneic threshold in neonates is very close to the eupneic PCO2, likely facilitating the appearance of periodic breathing and apnea. In contrast with adults, who need to be artificially hyperventilated to switch from regular to periodic breathing, neonates do this spontaneously. We therefore measured the apneic threshold as the average alveolar PCO2 (PaCO2) of the last three breaths of regular breathing preceding the first apnea of an epoch of periodic breathing. We also measured the PaCO2 of the first three breaths of regular breathing after the last apnea of the same periodic breathing epoch. In preterm infants, eupneic PaCO2 was 38.6 +/- 1.4 Torr, the preperiodic PaCO2 apneic threshold was 37.3 +/- 1.4 Torr, and the postperiodic PaCO2 was 37.2 +/- 1.4 Torr. In term infants, the eupneic PaCO2 was 39.7 +/- 1.1 Torr, the preperiodic PaCO2 apneic threshold was 38.7 +/- 1.0 Torr, and the postperiodic value was 37.9 +/- 1.2 Torr. This means that the PaCO2 apneic thresholds were 1.3 +/- 0.1 and 1.0 +/- 0.2 Torr below eupneic PaCO2 in preterm and term infants, respectively. The transition from eupneic PaCO2 to PaCO2 apneic threshold preceding periodic breathing was accompanied by a minor and nonsignificant increase in ventilation, primarily related to a slight increase in frequency. The findings suggest that neonates breathe very close to their PCO2 apneic threshold, the overall average eupneic PCO2 being only 1.15 +/- 0.2 Torr (0.95-1.79, 95% confidence interval) above the apneic threshold. This value is much lower than that reported for adult subjects (3.5 +/- 0.4 Torr). We speculate that this closeness of eupneic and apneic PCO2 thresholds confers great vulnerability to the respiratory control system in neonates, because minor oscillations in breathing may bring eupneic PCO2 below threshold, causing apnea.     

Effects on breathing of rostral pons glutamate injection during opossum development

To determine whether pathways from the rostral pons, capable of influencing breathing, were present in immature mammals, the excitatory amino acid glutamate (sodium salt) was pressure injected in very small volumes into the rostral pons of suckling and adult opossums. The youngest animals tested were approximately 3 wk old (1.5-2.9 g). Animals were anesthetized with the thiobarbituric acid derivative, Inactin, and the electromyogram of the diaphragm was used to assess changes in breathing rhythm and ventilatory output. Glutamate concentrations of 50, 150, and 1,000 mM were injected into the rostral pons. Active sites were generally located between parabrachial and either lateral lemniscal or trigeminal nuclei. Effects of glutamate in opossums of all ages included changes in diaphragm activity and respiratory timing over several breaths. In the youngest animals, a very high incidence of apnea occurred as an initial response (17 of 20 sites) at the 1,000 mM concentration. The high incidence of apneic response in the youngest animals suggests that strong activation of rostral pontine neurons can more easily disrupt respiratory output; a physiological circumstance of such activation might include a diving response stimulated by trigeminal afferents.     

Respiratory reflex responses to stimulation of tracheal mucosa in enflurane-anesthetized humans

We investigated respiratory reflex responses to tracheal mucosa stimulation induced by injection of distilled water in 13 female patients under three different depths of enflurane anesthesia (0.7, 1.0, and 1.3 minimum alveolar concentration). Detailed analysis of the types of reflex responses revealed that there are at least six different responses: 1) the apneic reflex, 2) the expiration reflex, 3) spasmodic, panting breathing, 4) the cough reflex, 5) slowing of breathing, and 6) rapid, shallow breathing. Among these reflex responses, the cough reflex was the most sensitive and the apneic reflex followed by slowing of breathing was the most resistant to deepening anesthesia, whereas the sensitivity of other types of reflex responses was in between. Our results indicate that the types of respiratory reflex responses to tracheal mucosa stimulation are associated with depths of anesthesia and that the differences in sensitivity to anesthesia may be a valuable sign in clinical assessment of depth of anesthesia.     

Albumin transcytosis from the pleural space.

Occurrence of transcytosis in pleural mesothelium was verified by measuring removal of labeled macromolecules from pleural liquid in experiments without and with nocodazole. To this end, we injected 0.3 ml of Ringer-albumin with 750 microg of albumin-Texas red or with 600 microg of dextran 70-Texas red in the right pleural space of anesthetized rabbits, and after 3 h we measured pleural liquid volume, labeled macromolecule concentration, and, hence, labeled macromolecule quantity in the liquid of this space. Labeled albumin left was 318 +/- 28 microg in control and 419 +/- 17 microg in nocodazole experiments (means +/- SE); hence, whereas ventilation was similar its removal was greater (P < 0.01) in control experiments. Labeled dextran left was 283 +/- 10 microg in control and 381 +/- 21 microg in nocodazole experiments; hence, whereas ventilation was similar its removal was greater (P < 0.01) in control experiments. These findings indicate occurrence of transcytosis from the pleural space. Liquid removed by transcytosis was 0.05 ml/h. This amount times unlabeled albumin concentration under physiological conditions (10 mg/ml) times lumen-vesicle partition coefficient for albumin (0.78) provides fluid-phase albumin transcytosis: approximately 203 microg. h(-1) kg(-2/3). Transcytosis might contribute a relevant part of protein and liquid removal from the pleural space.