Biomedical subjects
L Zocchi
Publications and source records attributed to L Zocchi.
Physiology and pathophysiology of pleural fluid turnover.
Tight control of the volume and composition of the pleural liquid is necessary to ensure an efficient mechanical coupling between lung and chest wall. Liquid enters the pleural space through the parietal pleura down a net filtering pressure gradient. Liquid removal is provided by an absorptive pressure gradient through the visceral pleura, by lymphatic drainage through the stomas of the parietal pleura, and by cellular mechanisms. Indeed, contrary to what was believed in the past, pleural mesothelial cells are metabolically active, and possess the cellular features for active transport of solutes, including vesicular transport of protein. Furthermore, the mesothelium was shown, on the basis of recent experimental evidence, both in vivo and in vitro, to be a less permeable barrier than previously believed, being provided with permeability characteristics similar to those of the microvascular endothelium. Direct assessment of the relative contribution of the different mechanisms of pleural fluid removal is difficult, due to the difficulty in measuring the relevant parameters in the appropriate areas, and to the fragility of the mesothelium. The role of the visceral pleura in pleural fluid removal under physiological conditions is supported by a number of findings and considerations. Further evidence indicates that direct lymphatic drainage through the stomas of the parietal pleura is crucial in removing particles and cells, and important in removing protein from the pleural space, but should not be the main effector of fluid removal. Its importance, however, increases markedly in the presence of increased intrapleural liquid loads. Removal of protein and liquid by transcytosis, although likely on the basis of morphological findings and suggested by recent indirect experimental evidence, still needs to be directly proven to occur in the pleura. When pleural liquid volume increases, an imbalance occurs in the forces involved in turnover, which favours fluid removal. In case of a primary abnormality of one ore more of the mechanisms of pleural liquid turnover, a pleural effusion ensues. The factors responsible for pleural effusion may be subdivided into three main categories: those changing transpleural pressure balance, those impairing lymphatic drainage, and those producing increases in mesothelial and capillary endothelial permeability. Except in the first case, pleural fluid protein concentration increases above normal: this feature underlies the classification of pleural effusions into transudative and exudative.
Electrical resistance and ion diffusion through mesothelium.
(1) Since phospholipids (PHL) added on the luminal side of specimens of parietal pericardium of rabbits decrease diffusional permeability (P) to Na+, but not to Cl-, P to Rb+, a cation with hydrated radius similar to that of Cl- was measured. P(Rb+) was 13.1 (+/-1.1, S.E.)x10(-5) cm/sec and it was not decreased by PHL. This suggests that PHL decrease size of intercellular "pores" of mesothelium, and restrict diffusion of solutes with radius>0.2 nm. (2) Electrical resistance (Re) of pericardium specimens was measured without PHL, with PHL, and after mesothelium was scraped away, to obtain Re of connective tissue and, thus, to compute Re of mesothelium. Re of connective tissue was 1.0+/-0.2 Omega cm(2); Re of mesothelium was 10.1+/-0.6 and 12.3+/-0.9 Omega cm(2) without and with PHL, respectively. The fraction of electrical current carried by Na+ indicates that Na+ diffusion through mesothelium without PHL is nearly free. (3) Re of cultured mesothelial cell monolayers of rat visceral pleura was 6.1+/-0.2 Omega cm(2), i.e. smaller than that of specimen mesothelium; it did not increase with PHL. P(Na+) of cultured mesothelial cell monolayers was 20.0x10(-5) cm/sec, i.e. greater than that of specimen mesothelium.
Macromolecule transfer through mesothelium and connective tissue.
Diffusional permeability (P) to inulin (P(in)), albumin (P(alb)), and dextrans [70 (P(dx 70)), 150 (P(dx 150)), 550 (P(dx 550)), and 2, 000 (P(dx 2,000))] was determined in specimens of parietal pericardium of rabbits, which may be obtained with less damage than pleura. P(in), P(alb), P(dx 70), P(dx 150), P(dx 550), and P(dx 2, 000) were 0.51 +/- 0.06 (SE), 0.18 +/- 0.03, 0.097 +/- 0.021, 0. 047 +/- 0.011, 0.025 +/- 0.004, and 0.021 +/- 0.005 x 10(-5) cm/s, respectively. P(in), P(alb), and P(dx 70) of connective tissue, obtained after removal of mesothelium from specimens, were 10.3 +/- 1.42, 2.97 +/- 0.38, and 2.31 +/- 0.16 x 10(-5) cm/s, respectively. Hence, P(in), P(alb), and P(dx 70) of mesothelium were 0.54, 0.20, and 0.10 x 10(-5) cm/s, respectively. Inulin (like small solutes) fitted the relationship P-solute radius for restricted diffusion with a 6-nm "pore" radius, whereas macromolecules were much above it. Hence, macromolecule transfer mainly occurs through "large pores" and/or transcytosis. In line with this, the addition of phospholipids on the luminal side (which decreases pore radius to approximately 1.5 nm) halved P(in) but did not change P(alb) and P(dx 70). P(in) is roughly similar in mesothelium and capillary endothelium, whereas P to macromolecules is greater in mesothelium. The albumin diffusion coefficient through connective tissue was 17% of that in water. Mesothelium provides 92% of resistance to albumin diffusion through the pericardium.
Equivalent radius of paracellular "pores" of the mesothelium.
Diffusional permeability (P) to water (P(w)), Cl(-) (P(Cl(-))), and mannitol (P(man)) was determined in specimens of rabbit parietal pericardium without and with phospholipids added on the luminal side, as previously done with sucrose and Na(+). P to the above-mentioned molecules and to Na(+) (P(Na(+))) was also determined after mesothelium was scraped away from specimens. P(w), P(Cl(-)), P(Na(+)), and P(man) of connective tissue were the following (x10(-5) cm/s): 73.1 +/- 7.3 (SE), 59.5 +/- 4.5, 41.7 +/- 3.4, and 23.4 +/- 2.4, respectively. From these and corresponding data on integer pericardium, P(w), P(Cl(-)), P(Na(+)), and P(man) of mesothelium were computed. They were the following: 206, 17.9, 9.52, and 3.93, and 90.2, 14.4, 4.34, and 1.75 x 10(-5) cm/s without and with phospholipids, respectively. As previously found for P to sucrose, P to solutes is smaller in mesothelium than in connective tissue, although the latter is approximately 35-fold thicker; instead, P(w) is higher in mesothelium, suggesting marked water diffusion through cell membrane. Equivalent radius of paracellular "pores" of mesothelium was computed with two approaches, disregarding P(w). The former, a graphical analysis on a P-molecular radius diagram, yielded 6.0 and 1.7 nm without and with phospholipids, respectively. The latter, on the basis of P(man), P to sucrose, and function for restricted diffusion, yielded 7.8 and 1. 1 nm, respectively.
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.
Diffusional permeability of rabbit mesothelium.
Diffusional permeability (P) to sucrose (Psuc) and Na+ (PNa+) was determined in specimens of rabbit sternal parietal pericardium, which may be obtained without stripping. Specimens were mounted in an Ussing apparatus with 3H-labeled sucrose and 22Na+ in a luminal (L) or interstitial (I) chamber. Psuc was 2.16 +/- 0.44 for L-->I and 2.63 +/- 0.45 (SE) x 10(-5) cm/s for I-->L, i.e., approximately 10 times smaller than that previously obtained in stripped specimens of pleura despite the similarity of intercellular junctions in pericardium and pleural mesothelium of various species. These findings suggest that previous Psuc was overestimated because stripping damages the mesothelium. PNa+ (x10(-5) cm/s) was 7.07 +/- 0.71 for L-->I and 7.37 +/- 0.69 x 10(-5) cm/s for I-->L. Measurements were also done with phospholipids, which are adsorbed on the luminal side of mesothelium in vivo. With phospholipids in L, Psuc was 0.75 +/- 0.10 and 0.65 +/- 0.08 and PNa+ was 3.80 +/- 0.32 and 3.76 +/- 0.15 x 10(-5) cm/s for L-->I and I-->L, respectively, i. e., smaller than without phospholipids. With phospholipids in I (where they are not adsorbed), Psuc (2.33 +/- 0.42 x 10(-5) cm/s) and PNa+ (7.01 +/- 0.45 x 10(-5) cm/s) were similar to those values without phospholipids. Hence, adsorbed phospholipids decrease P of mesothelium. If the mesothelium were scraped away from the specimen, Psuc of the connective tissue would be 13.2 +/- 0.76 x 10(-5) cm/s. Psuc of the mesothelium, computed from Psuc of the unscraped and scraped specimens, corrected for the effect of unstirred layers (2. 54 and 19.4 x 10(-5) cm/s, respectively), was 2.92 and 0.74 x 10(-5) cm/s without and with phospholipids, respectively. Hence, most of the resistance to diffusion of the pericardium is provided by the mesothelium.
Effect of adrenaline and alpha-agonists on net rate of liquid absorption from the pleural space of rabbits.
Indirect evidence supporting a solute-coupled liquid absorption from the pleural space of rabbits has recently been provided; moreover, the beta 2-adrenoceptor agonist terbutaline has been found to increase this absorption. In this study the effect of adrenaline and alpha-adrenoceptor agonists on net rate of liquid absorption (Jnet) from albumin Ringer hydrothoraces of various sizes has been determined in anaesthetized rabbits. In hydrothoraces with adrenaline (5 x 10(-6) M) the relationship between Jnet and volume of liquid injected was displaced upwards by 0.09 ml h-1 relative to that in control hydrothoraces (P < 0.01). This displacement did not occur with lower adrenaline concentrations or after pretreatment with the beta-blocker propranolol. Hence, this increase in Jnet is mediated by stimulation of beta-receptors. It seems to be caused by an increase in solute-coupled liquid absorption, since beta-agonists inhibit lymphatic activity while, at relatively high concentrations, they may increase active transport. Conversely, the strong stimulation of lymphatic alpha-receptors that should occur with adrenaline after beta-blockade may fail to increase lymphatic drainage, because it has been shown that the increase in contraction frequency of lymphatics may be balanced by the decrease in their stroke volume. Arterial blood pressure during the hydrothoraces with adrenaline was unchanged. In hydrothoraces with the alpha 2-agonist clonidine (5 x 10(-6) M; a less potent agent than adrenaline) the slope of the relationship between Jnet and volume injected increased by 26% (P < 0.01), while its origin did not change. This increase in slope did not occur with a lower clonidine concentration or after pretreatment with the alpha-blocker phentolamine. Hence, it is caused by stimulation of alpha 2-receptors, which probably lead to an increase in lymphatic drainage related to liquid load. In hydrothoraces with the alpha 1-agonist phenylephrine (5 x 10(-6) or 10(-7) M) Jnet was simlar to control values.
[Intravascular surgery in the treatment of peripheral arteriopathies: our experience].
The Authors, through a review of their vascular surgery experience in the treatment of PAOD at the III General Surgery Institute directed by Prof. G. Di Matteo (University, of Rome), focus their attention on endovascular surgery. Initially considered as an effective complement to "traditional surgery" rapidly its role has grown as an effective alternative for a number of vascular patients.
Effect on phloridzin on net rate of liquid absorption from the pleural space of rabbits.
Previous indirect findings have suggested the occurrence of solute-coupled liquid absorption from the pleural space, consistent with Na(+)-K(+)-ATPase on the interstitial side plus a Na(+)-H+ and CI(-)-HCO3- double exchange on the luminal side of the pleural mesothelium. To assess whether Na(+)-glucose cotransport also operates on the luminal side, the relationship between net rate of liquid absorption from the right pleural space (Jnet) and volume of liquid injected into this space (0.5, 1 or 2 ml) was determined in anaesthetized rabbits during hydrothoraces with phloridzin (10(-3)M) or with phloridzin plus 4-acetamido-4'-isothiocyanatostilbene-2, 2'-disulphonic acid (SITS; 1.5 x 10(-4)M). The relationship obtained during hydrothoraces with phloridzin was displaced downwards by 0.09 ml h-1 relative to that in control hydrothoraces (P < 0.01). The decrease in Jnet was similar in hydrothoraces of various sizes. The relationship obtained in hydrothoraces with phloridzin plus SITS was displaced downwards by 0.16 ml h-1 relative to that in control hydrothoraces (P < 0.01), i.e. the decrease in Jnet was similar to the sum (0.17 ml h-1) of the decreases in Jnet produced individually by phloridzin and by SITS (0.08 ml h-1). The decrease in Jnet was similar in hydrothoraces of differing size. The above findings are consistent with the occurrence of Na(+)-glucose cotransport on the luminal side of the pleural mesothelium, operating simultaneously with the double exchange also under physiological conditions.
Beta-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.
Mechanisms involved in pleural liquid turnover.
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Effects of beta-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.
Active Na+ transport and 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.
Effect of pressure and timing of contraction on human rib cage muscle fatigue.
Breathing against inspiratory loads can be accomplished with different degrees of coupling between the diaphragm and the other muscles attached to the rib cage (RCM). Thus, the electromyographic signs of fatigue develop separately in each muscle group. While breathing with diaphragm emphasis, the occurrence of diaphragmatic fatigue was found to be related to the tension-time index TTdi (= Pdi/Pdimax x Ti/Ttot). Above the critical range of 0.15 to 0.18, the endurance of the diaphragm is less than 1 h and it is inversely related to the TTdi value. However, in most loaded breathing conditions, the spontaneous pattern of breathing is characterized by predominant activation of RCM. The tension-time conditions at which fatigue develops during breathing with RCM emphasis are not known. We assessed the critical tension-time value in four normal subjects breathing with RCM emphasis against inspiratory threshold loads. RCM predominance was achieved by developing negative abdominal pressure swings during inspiration, and it was characterized by the tension-time index TTrc (Ppl/Pplmax x Tl/Ttot), where Ppl is pleural pressure developed under this condition. Above a critical TTrc value of 0.30, endurance time was inversely related to TTrc, and it resulted from failure of the RCM rather than of the diaphragm. We conclude that the critical threshold, as assessed by TTrc, is higher for breathing patterns with RCM emphasis than previously described by TTdi for diaphragm emphasis. However, when predominantly recruited, as in breathing patterns commonly adopted in loaded conditions, the RCM fatigue earlier than the diaphragm.
[The changes in the sexual behavior of patients undergoing aorto-iliac revascularization].
A correct approach to sexual disorders in vascular patients presupposes an accurate investigation before and after operation. The authors evaluate the reliability of the diagnostic methods used, pre- and postoperatively, to ascertain sexual disorders, and analyse the influence of surgery on sexual function.
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.
Thrombotic and hemorrhagic complications in essential thrombocythemia. A retrospective study of 103 patients.
A retrospective study of 103 patients with essential thrombocythemia was carried out to evaluate the incidence of thrombohemorrhagic complications and establish whether there were any correlations between these events and clinical or laboratory data. At onset or during the course of the disease, 26 patients (25.2%) presented thrombotic and 12 (11.6%) hemorrhagic complications: among the latter, six patients had gastrointestinal bleeding during antiaggregant therapy. No significant correlations were observed between thrombohemorrhagic complications and platelet count, age, sex, platelet function, bleeding time, or therapeutic regimen. However, there was a statistically significant correlation between a positive patient history for thrombotic events and an increase in thromboses. In agreement with other authors, it is believed that the best approach in asymptomatic patients is strict surveillance without treatment. Chemotherapy and/or treatment with antiaggregant agents should be reserved for symptomatic patients or patients with a positive history for thrombotic events.