The pulmonary interstitium is a pathway that drains microvascular filtrate from the lung. Thus its properties are important to the understanding how normal fluid balance is maintained and the pathogenesis of pulmonary edema. The clearance of interstitial fluid depends on bulk flow caused by differences in hydrostatic pressure and osmotic flow caused by differences in protein concentration. In previous studies, the effects of hydration, protein concentration, fluid viscosity, electric charge, and hyaluronidase on interstitial conductivity were measured. The effects of albumin and hyaluronidase were opposite to those expected from steric exclusion in solutions of albumin and hyaluronan. Recent studies indicated interstitial sieving of albumin and a finite reflection coefficient that increased at low concentrations with normal hydration, in conjunction with free diffusion of albumin. Such a membrane-like property is opposite to the properties of solutions usually assigned to interstitium. A major goal is to describe the interstitium in terms of its membrane properties. The effect of hyaluronidase on interstitial sieving of albumin and the effect of hydration on the reduced diffusive response to hyaluronidase will be studied. The sieving behavior measured in interstitial segments during steady state flow will be supported by studies of the longitudinal gradient in albumin concentration during interstitial cuff growth in liquid-inflated .lungs. These studies will measure steric exclusion of albumin in interstitial cuffs of vessels ranging from arterioles to large vessels.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL040362-16
Application #
6740800
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Program Officer
Denholm, Elizabeth M
Project Start
2001-07-01
Project End
2006-05-31
Budget Start
2004-06-01
Budget End
2006-05-31
Support Year
16
Fiscal Year
2004
Total Cost
$144,800
Indirect Cost
Name
University of Kentucky
Department
Biomedical Engineering
Type
Other Domestic Higher Education
DUNS #
939017877
City
Lexington
State
KY
Country
United States
Zip Code
40506
Lai-Fook, Stephen J; Houtz, Pamela K; Jones, Philip D (2005) Transdiaphragmatic transport of tracer albumin from peritoneal to pleural liquid measured in rats. J Appl Physiol 99:2212-21
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
Villarruel, Sandra; Ibbott, Geoffrey S; Lai-Fook, Stephen J (2002) Effect of concentration and hydration on restriction of albumin by lung interstitium. Microvasc Res 63:27-40
Lai-Fook, S J; Hyatt, R E (2000) Effects of age on elastic moduli of human lungs. J Appl Physiol 89:163-8
Wang, P M; Lai-Fook, S J (2000) Pleural tissue hyaluronan produced by postmortem ventilation in rabbits. Lung 178:12-Jan

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