The goal of this research is to study some of the mechanical factors affecting the normal physiology of pleural liquid exchange and their relationship to lung static recoil. Classical studies have postulated that pleural liquid pressure is less than pleural surface pressure (lung static recoil) and that pleural liquid is in hydrostatic equilibrium (1 cm H20/cm height). The more negative pleural liquid pressure is presumed to be the result of an absorptive mechanism which reduced the pleural liquid until the pleural surfaces make contact. We will re-examine these postulates using new techniques. We developed two relatively noninvasive techniques for measureing pleural liquid pressure: the micropipet-servonulling and the rib capsule techniques. Measurement in rabbits and dogs indicate that pleural liquid pressure is not in static equilibrium but show a vertical gradient of less than 1 cmH20/cm. Measurements of pleural liquid thickness by a new method using light microscopy show no contact between the two pleurae. We shall use these techniques to explore the relationship between pleural liquid pressure, pleural liquid thickness and lung height. First, we shall measure by micropuncture the vertical gradient in pleural liquid pressure in the prone and supine dog. Second, we shall compare pleural liquid pressure in the lobar margins and on the diaphragmatic surface with the pressure over the costal surface. Also we shall measure pleural thickness at the fissure by light microscopy. Third, we found that the pleural space thickness measured using light microscopy in 5 species increased with animal size. We will extend these measurements to a larger species, the sheep. Fourth, we will measure by a gamma camera the pleural liquid thickness and the dynamics of pleural liquid. Our results suggest that the dynamics of pleural liquid is important. Recently, we proposed a theory of pleural liquid exchange which includes viscous flow within the pleural space. Pleural liquid exchange is governed by the laws of liquid and solute exchange across the microvasclar barrier. The viscous flow is driven by regional differences in pleural surface pressure and gravity. Pleural liquid pressure equals surface pressure. In the steady state the exchange rate equals the viscous flow which is a funciton of the pleural space thickness. To test our hypothesis, we will measure pleural liquid thickness, microvascular pressure and pleural liquid protein concentration in spontaneously hypertensive rats (SHR) and control normotensive rats (WKY). Elevation in blood pressure should increase flow, increase thickness, and decrease protein concentration.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
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Respiratory and Applied Physiology Study Section (RAP)
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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Lai-Fook, Stephen J; Houtz, Pamela K (2008) Airway constriction measured from tantalum bronchograms in conscious mice in response to methacholine. J Appl Physiol 105:933-41
Lai-Fook, Stephen J; Houtz, Pamela K; Lai, Yih-Loong (2008) End-expiratory and tidal volumes measured in conscious mice using single projection x-ray images. J Appl Physiol 104:521-33
Tang, Sonja M Moe; Lai-Fook, Stephen J (2005) Transport properties of the mesothelium and interstitium measured in rabbit pericardium. Microvasc Res 70:152-64
Houtz, P K; Jones, P D; Aronson, N E et al. (2004) Effect of pancreatic and leukocyte elastase on hydraulic conductivity in lung interstitial segments. J Appl Physiol 97:2139-47
Moe, Sonja M; Conhaim, Robert L; Lai-Fook, Stephen J (2004) Interstitial albumin concentration measured during growth of perivascular cuffs in liquid-filled rabbit lung. J Appl Physiol 96:283-92
Lai-Fook, Stephen J (2004) Pleural mechanics and fluid exchange. Physiol Rev 84:385-410
Moe, Sonja M; Lai-Fook, Stephen J (2003) Effect of concentration on restriction and diffusion of albumin in the excised rat diaphragm. Microvasc Res 65:96-108
Aronson, N E; Houtz, P K; Villarruel, S et al. (2003) Effect of concentration and hyaluronidase on restriction of hetastarch flux through lung interstitial segments. Microvasc Res 66:218-26
Wang, P M; Lai-Fook, S J (2000) Pleural tissue hyaluronan produced by postmortem ventilation in rabbits. Lung 178:12-Jan
Parameswaran, S; Brown, L V; Ibbott, G S et al. (1999) Hydraulic conductivity, albumin reflection and diffusion coefficients of pig mediastinal pleura. Microvasc Res 58:114-27

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