Luciano Zocchi

MECHANICAL COUPLING AND LIQUID EXCHANGES IN THE PLEURAL SPACE

The pleural space provides the mechanical coupling between lung and chest wall: two views about this coupling are reported and discussed. Information on volume, composition, thickness, and pressure of the pleural liquid under physiologic conditions in a few species is provided. The Starling pressures of the parietal pleura filtering liquid into pleural space, and those of the visceral pleura absorbing liquid from the space are considered along with the permeability of the mesothelium. Information on the lymphatic drainage through the parietal pleura and on the solute-coupled liquid absorption from the pleural space under physiologic conditions and with various kinds of hydrothorax are provided.

Solute-coupled liquid absorption from the pleural space

The occurrence of a solute-coupled absorption of liquid from the pleural space was studied by measuring in anesthetized rabbits the volume of liquid of the right pleural space 1 h after injecting into it 2 ml of Ringer solution or of Ringer with an inhibitor of a Na(+)-Cl- coupled transport or of the Na+/K+ pump. Volume collected after Ringer was 1.56 +/- 0.08 ml. Initial volume being 2.2 ml, net absorption rate was 0.64 ml/h. Volume collected after disulfonic stilbene (0.1 mM) or bumetanide (0.1 mM) was 2.01 +/- 0.06 and 2.01 +/- 0.05 ml, respectively; net absorption rate was reduced to 0.19 ml/h. This suggests the occurrence of Na(+)-Cl- coupled transports. Volume collected after ouabain (0.5 mM) was 2.08 +/- 0.08 ml; net absorption rate was reduced to 0.12 ml/h. This suggests the occurrence of the Na+/K+ pump. The marked reduction in the hydrothorax absorption produced by the inhibitors shows the occurrence of a solute-coupled liquid absorption from the pleural space. Liquid absorbed through the visceral pleura by the solute-coupled transport should be removed by the Starling forces of pulmonary capillaries. Solute-coupled absorption of liquid through the parietal pleura should oppose the filtration caused by the Starling forces.

Electrolyte transport across the pleura of rabbits

The amounts of Na+ and Cl- in the right pleural space of anesthetized rabbits were determined 10 and 60 min after a 2 ml hydrothorax with the following solutions: Ringer, Ringer with an inhibitor of the Na(+)-Cl- coupled transport or of the Na+/K+ pump, Ringer with gluconate instead of Cl- or with methylglucamine instead of Na+. During the 10-60 min period: (a) with Ringer Na+ and Cl- decreased (P less than 0.01) along with an iso-osmotic liquid absorption, (b) with disulfonic-stilbene (0.1 mM), amiloride (0.7 mM), acetazolamide (0.1 mM), or ouabain (0.5 mM) Na+ did not change and Cl- decreased less (P less than 0.01) than with Ringer. With gluconate-Ringer or methylglucamine-Ringer the liquid flow reversed: in the former case Cl- and, to a smaller extent, Na+ increased (P less than 0.01); in the latter only Na+ increased (P less than 0.01). These findings suggest: (1) the occurrence of a Na+/H+ and Cl-/HCO3- double exchange on the serosal side and of a Na+/K+ pump on the interstitial side of the pleural mesothelium; (2) a slow efflux from the pleural space of gluconate or methylglucamine relative to the corresponding influx of Cl- or Na+, respectively; this drags liquid into the space by osmotic gradient.

Active Na+ transport coupled liquid outflow from hydrothoraces of various size

The net rate of liquid flow and Na+ flux across the pleura was determined in anesthetised rabbit during hydrothoraces 0.5 to 5 ml in size, without and with amiloride. In the hydrothoraces with amiloride the net liquid flow and Na+ flux reversed when the volume injected approached zero. This indicates that the active Na+ transport and the consequent liquid absorption occur also under physiological conditions. The difference between the data obtained without and with amiloride provides the net solute-coupled liquid outflow and active Na+ efflux. These parameters increased linearly with the hydrothorax size up to 2 ml (0.39 ml/h and 54 muEq/h, respectively), and then levelled off. The linear relationship allowed their extrapolation to physiological conditions: 0.15 ml/h (0.07 ml.h-1.kg-1) and 21 muEq/h (0.1 muEq.h-1.cm-2). The increase in these parameters with the hydrothorax size seems due to the protein dilution caused by the Ringer injection, because it did not occur if Ringer was added with albumin to keep the protein concentration in the pleural liquid similar to that under physiological conditions.

Pleural liquid pressure in the zone of apposition and in the lung zone

Pleural liquid pressure in zone of apposition (Pliq,ap) and in lung zone (Pliq,L) was measured simultaneously through liquid filled cannulas in anesthetized dogs in lateral posture. At top Pliq,ap and Pliq,L at iso-height were -9.7 +/- 0.4 and -11.9 +/- 0.3 cm H2O, respectively, at end expiration (eE; P of delta less than 0.01; 11 dogs); -9.6 +/- 0.7 and -19.8 +/- 0.7 cm H2O at end inspiration (eI). At bottom they were -0.6 +/- 0.2 and -2.4 +/- 0.4 cm H2O, respectively, at eE (P of delta less than 0.05; 4 dogs); -1.5 +/- 0.3 and -8.5 +/- 1.0 cm H2O at eI. Vertical gradient of Pliq,ap was -0.97 +/- 0.02 cm H2O/cm. A 132% increase in ventilation (after 10 min dead space breathing) did not change eE and eI Pliq,ap, and eE Pliq,L, but decreased eI Pliq,L. These results imply: (1) no transmission to zone of apposition of tidal changes in Pliq,L; (2) a liquid flow from zone of apposition to lung zone; (3) a net filtration into zone of apposition. They suggest that absorption pressure of capillaries of visceral pleura is greater than that of lymphatics of zone of apposition. Lymphatic role in setting Pliq,L is discussed.

Liquid volume, Na+ and mannitol concentration in a hypertonic mannitol-Ringer hydrothorax

In anesthetised rabbits with a 2 ml hypertonic mannitol-Ringer hydrothorax in the right space 30 mM/L mannitol were required for an unchanged volume of the hydrothorax after 60 min. [Na+] in the pleural liquid 10, 30 and 60 min after this hydrothorax was 8, 7 and 5 mEq/L, respectively, lower (P less than 0.01) than the initial one and that in a Ringer-hydrothorax. This seems due to the active transport of Na+ out of the pleural space followed by little water because of the osmotic pressure exerted by mannitol. This finding provides further evidence for an active transport without using inhibitors, and implies that the mesothelium offers an appreciable resistance to small solute diffusion. Mannitol concentration, measured at corresponding times from the activity of labeled mannitol, was 76, 68 and 56%, respectively, of the initial one (24.5 mM/L). From 30 to 60 min 6.5 microM of mannitol left the right space mainly by diffusion. The diffusional permeability of the mesothelium was indirectly assessed from the diffusional outflux of mannitol, the surface of the pleural space, and an estimate of mannitol concentration in the interstitium next to the mesothelium: it is smaller than that found in vitro.

β-Agonist activation of an amiloride-insensitive transport mechanism in rabbit pleura

The beta-agonist terbutaline increases the net rate of liquid absorption from hydrothoraces with albumin-Ringer solution: since beta-agonists decrease lymphatic drainage, the effect of terbutaline seems due to an increase in solute-coupled liquid absorption, (Zocchi et al. 1994 Respir. Physiol. 97:347-356). In this research we determined in anesthetized rabbits the rate of volume change in albumin-Ringer hydrothoraces of different size with amiloride plus terbutaline, and compared it with that previously obtained in hydrothoraces with amiloride alone. The net rate of liquid absorption was 0.09 ml/h greater (P < 0.01) with amiloride plus terbutaline than with amiloride alone. This indicates that terbutaline activates an amiloride-insensitive mechanism of Na+ transport. The increase in net rate of liquid absorption produced by terbutaline persisted with bumetanide 10(-6) M and SITS 10(-4) M, disappeared almost completely with bumetanide 10(-5) M, and completely with furosemide 10(-3) M. These findings suggest that the mechanism activated by terbutaline, when the amiloride-sensitive mechanisms of the pleura have been blocked, is a Na(+)-K(+)-2 Cl- or Na(+)-Cl- symport little sensitive to bumetanide.

Effects of β-adrenergic blockade or stimulation on net rate of hydrothorax absorption

We determined in anesthetised rabbits the net rate of liquid absorption (NRLA) from Ringer or 1% albumin-Ringer hydrothoraces with the beta-blocker propranolol (or nadolol) or the beta-agonist terbutaline. The beta-blocker reduced NRLA by 38% in 2 ml Ringer hydrothoraces, and did not change it in 2 ml albumin-Ringer hydrothoraces; hence, with beta-blocker NRLA became similar in both kinds of hydrothorax (0.31 +/- 0.02 ml/h). Terbutaline decreased NRLA by 25% in 2 ml Ringer hydrothoraces, and increased it by 29% in 2 ml albumin-Ringer hydrothoraces; hence, with terbutaline NRLA became similar in both kinds of hydrothorax (0.40 +/- 0.02 ml/h), and 25% higher than with beta-blocker. Because beta-adrenoreceptor activity inhibits lymphatic smooth muscles and may increase Na+ transport in epithelia, these results suggest that: (1) pleural mesothelium is provided with beta-receptors, which increase Na+ transport and seem activated by protein dilution, (2) beta-receptors of the pleural lymphatics are essentially silent with and without protein dilution, (3) the lymphatic drainage produced by smooth muscle activity is smaller than the increase in solute-coupled liquid absorption caused by mesothelium beta-receptors.

Starling forces and lymphatic drainage in pleural liquid and protein exchanges

Pleural liquid volume and protein concentration (C) were determined in rabbits 60 min after a 2 ml hydrothorax with various albumin concentrations in Ringer, homologous serum or plasma. The absorption rate of the hydrothorax decreased with the increase in colloid osmotic pressure of the pleural liquid (pi), being 0.56 +/- 0.03, 0.32 +/- 0.02 and 0.17 +/- 0.05 ml/h with Ringer, 1.1 and 3 g% albumin, respectively, and nil with 5% albumin, serum or plasma. C increased with Ringer and 1.1% albumin, did not change with 3% albumin, and decreased with 5% albumin, serum or plasma. The protein content in the pleural liquid increased with Ringer, did not change with 1.1% albumin, and decreased with the other hydrothoraces. These findings indicate that with hydrothoraces of this size: (1) the Starling forces plus the solute-coupled liquid absorption [Agostoni and Zocchi (1990) Respir. Physiol. 81: 19-28] provide most of the pleural liquid absorption when pi is less than or equal to physiological; (2) the lymphatic drainage increases with pi, providing most of the liquid outflow when pi is similar to that of plasma. This increase in lymphatic drainage, however, does not compensate for the effects of the changes in Starling forces produced by the increased pi.

Pleural pressure from abdominal to pulmonary rib cage: sweep of the lung border

Pleural pressure was measured by a capsule placed in the superior part of right 8th or 9th intercostal space of dogs in left lateral posture. Transit of lung border was observed through endothoracic fascia at sides of the capsule. During inspiration the capsule membrane faced sequentially: diaphragm, lung border, lung; vice versa during expiration. Pressure on the diaphragm at end expiration was -5.3 +/- 0.5 cm H2O, reflecting outward recoil of the rib cage. At transit of lung border during inspiration (bor. I) a marked negative pressure spike occurred; a smaller spike occurred at expiratory transit (bor. E). These spikes should reflect pleural liquid pressure at lung border. At bor. I lung volume and radial displacement of rib 9 or 10 were greater during active than passive ventilation, whereas at bor. E they were similar under both conditions. Hence, during spontaneous inspiration displacement of lung border lags behind lung and rib expansion. Speed of lung border (assessed from duration of negative spike) ranged from 0.8 to 2.3 cm/sec during spontaneous breathing. On average it was similar at bor. I and bor. E, while air flow was greater at bor. I.