The goal of this research is to study some of the mechanical factors affecting pleural pressure as they pertain to regional lung volume distribution and pleural liquid exchange. Regional lung volume distfibution is important to understanding the factors responsible for optimal gas exchange. The factors affecting pleural liquid exchange are important to understanding the etiology and pathogenesis of pleural effusions and to the efficient lubrication of the pleural surfaces. The first part of this proposal concerns the measurement of pleural liquid pressure as a reflection of regional lung volume. The factors responsible for the vertical-pleural pressure gradient in different body positions will be examined both experimentally and theoretically. In anesthetized animals, the effect of lung inflation on the regional lung expansion in different body positions will be measured using two techniques: measurement of pleural liquid pressure using rib capsules and measurement of alveolar size through pleural windows via videomicroscopy. Pleural pressure in the zone of apposition of the diaphragm to rib cage will be measured using fib capsules. The effects of body position and acceleration on regional lung expansion will be studied with a finite element model of the lung, chest wall and abdomen. Predictions of the pleural pressure gradient will be compared to experimental results. The second part of this proposal concerns the movement of pleural liquid within and through the pleural space. Pleural liquid pressure is governed by pleural surface pressure, the result of the interaction among the lung, chest wall and gravity. Thus the vertical gradient in pleural liquid pressure is less than hydrostatic, resuking in a net downward viscous flow of pleural liquid. In the steady state pleural liquid exchange rate equals the viscous flow, which is a function of the pleural space thickness. The effect of cardiogenic motion and ventilation on the movement of pleural liquid will be measured by injecting fluorescent microspheres and fluorescent liquid into the pleural space and following the movement of the fluorescent dye via videomicroscopy. The effect of hypertension on pleural capillary filtration will be examined by measuring in spontaneously hypertensive rats (SHR) pleural micmvascular pressure by micropuncture and the filtration rate by the movement of radioactive albumin from the blood into the pleural space.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL036597-06
Application #
3351676
Study Section
Pathology A Study Section (PTHA)
Project Start
1987-07-01
Project End
1995-06-30
Budget Start
1991-07-01
Budget End
1992-06-30
Support Year
6
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Kentucky
Department
Type
Other Domestic Higher Education
DUNS #
832127323
City
Lexington
State
KY
Country
United States
Zip Code
40506
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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