We propose to study blood-lymph transport of plasma proteins and other large molecules in normal animals and in animals with experimental disturbances of fluid and protein distribution, and also to study blood-tissue exchange of these substances in whole animals and in isolated perfused organs. Our goals are to find out how large molecules, especially albumin and immunoglobulins, move through the capillary endothelium and how they become distributed throughout the interstitial compartment. We are particularly interested in how macromolecular transport is coupled to fluid movement, how fluid balance between plasma and interstitium is controlled under normal and abnormal conditions, and how abnormalities of fluid and plasma protein exchange affect delivery of albumin and immunoglobulins to the tissues. Abnormal states to be investigated include acute and chronic hypoproteinemia, volume expansion with plasma or colloid substitute or saline fluid, venous congestion and chronic mild inflammation. We will explore the influence of molecular size, shape and charge on transport parameters (permeability-surface area products and reflection coefficients), and be on the lookout for specific transport affinities for individual plasma proteins. An important part of our plan is to advance theoretical analysis of blood-tissue-lymph exchange in order to evaluate capillary transport pathwasy and interstitial barriers. Our investigations will further understanding of plasma and interstitial fluid volume control under normal conditions, and of how these control mechanisms are affected in edematous states (congestive heart failure, hypoproteinemia) or when plasma volume is restored with artificial colloid or saline fluids after blood loss. We hope to learn more about the ways in which the body resists development of edema, and how we may intervene more successfully to restore normal fluid and protein distribution.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL018010-12
Application #
3335515
Study Section
Cardiovascular and Pulmonary Research B Study Section (CVB)
Project Start
1975-01-01
Project End
1989-12-31
Budget Start
1986-01-01
Budget End
1986-12-31
Support Year
12
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of California Davis
Department
Type
Schools of Medicine
DUNS #
094878337
City
Davis
State
CA
Country
United States
Zip Code
95618
Renkin, E M; Tucker, V L (1998) Measurement of microvascular transport parameters of macromolecules in tissues and organs of intact animals. Microcirculation 5:139-52
Albert, T S; Tucker, V L; Renkin, E M (1997) Acute alveolar hypoxia increases blood-to-tissue albumin transport: role of atrial natriuretic peptide. J Appl Physiol 82:111-7
Aukland, K; Wiig, H; Tenstad, O et al. (1997) Interstitial exclusion of macromolecules studied by graded centrifugation of rat tail tendon. Am J Physiol 273:H2794-803
Albert, T S; Tucker, V L; Renkin, E M (1997) Atrial natriuretic peptide levels and plasma volume contraction in acute alveolar hypoxia. J Appl Physiol 82:102-10
Tucker, V L (1996) Contribution of ANP to plasma protein escape during VE: effects of thiorphan and atrial appendectomy. Am J Physiol 271:R610-8
Tucker, V L (1996) Plasma ANP levels and protein extravasation during graded expansion with equilibrated whole blood. Am J Physiol 271:R601-9
Tucker, V L; Bravo, E; Weber, C J et al. (1995) Blood-to-tissue albumin transport in rats subjected to acute hemorrhage and resuscitation. Shock 3:189-95
Wiig, H; Kaysen, G A; al-Bander, H A et al. (1994) Interstitial exclusion of IgG in rat tissues estimated by continuous infusion. Am J Physiol 266:H212-9
Renkin, E M; Wiig, H (1994) Limits to steady-state lymph flow rates derived from plasma-to-tissue uptake measurements. Microvasc Res 47:318-28
Aukland, K; Bogusky, R T; Renkin, E M (1994) Renal cortical interstitium and fluid absorption by peritubular capillaries. Am J Physiol 266:F175-84

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