The goal of this research is to study some factors that contribute to the formation of pleural liquid. The primary function of pleural liquid is lubrication of the pleural surfaces during breathing. Thus the mechanisms by which pleural liquid is formed in and cleared from the pleural space are important to understanding the pathogenesis of diseases, such as pleural effusions and pleural adhesions. Our recent studies in the excised rat diaphragm showed transport properties similar to those of pleural and other interstitial membranes and suggested that part of the pleural liquid might be derived from the peritoneal cavity via the diaphragm. Studies by other investigators have suggested a role for active mesothelial transport of liquid and protein. This proposal focuses on two areas. One is the contribution to pleural liquid and protein from the peritoneal cavity via the diaphragm relative to the contribution from the microcirculation. The transport of radioactive tracer albumin from the circulation into the pleural space, diaphragm, and peritoneal cavity will be measured in conscious rats. Other experiments will study transport from the peritoneal cavity into the diaphragm, circulation and pleural space. The effect of hypertension on transport will be studied using spontaneously hypertensive rats and its genetic normotensive control, the Wistar-Kyoto rat. The second area of research deals with the contribution of active transport of liquid and protein across pleural membrane relative to passive transport by diffusion and bulk flow. The pericardial membrane and diaphragm will be studied because these tissues are free standing, unlike the visceral and parietal pleurae that need to be stripped for in vitro studies. A specific objective is to develop a method to separate passive from active transport properties of pericardium and diaphragm, tissues that have both mesothelium and interstitium.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Respiratory Physiology Study Section (RESP)
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Denholm, Elizabeth M
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University of Kentucky
Biomedical Engineering
Other Domestic Higher Education
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
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
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; 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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