The proposed program is focused on mechanisms of transport of small solutes from the blood into the myocardium and in particular on the characterization of transport across the capillary wall, via trans- and inter-endothelial cell routes. Previous work has gone a long way in obtaining clear mathematical descriptions of intravascular and transcapillary transport. The new emphasis is on the mechanisms of transport, particularly for fatty acids and adenosine into or across endothelial cells via facilitated or passive mechanisms. The multiple indicator dilution technique will be used to evaluate the unidirectional plasmalemmal fluxes of adenosine and fatty acids. Specific experiments will be done to test the hypothesis that the membrane transporters for adenosine and inosine can behave as facilitating countertransporters, that is, show augmentation of cis to trans flux by raising the trans-concentrations. The program should result in proven new techniques for estimating fluxes across endothelial cell walls in intact organs and provide data on specific solutes in the myocardium of dogs and rabbits.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37HL019139-15
Application #
3485627
Study Section
Cardiovascular and Renal Study Section (CVB)
Project Start
1977-12-01
Project End
1991-06-30
Budget Start
1990-07-01
Budget End
1991-06-30
Support Year
15
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Washington
Department
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Yipintsoi, Tada; Kroll, Keith; Bassingthwaighte, James B (2016) Fractal regional myocardial blood flows pattern according to metabolism, not vascular anatomy. Am J Physiol Heart Circ Physiol 310:H351-64
Bassingthwaighte, James B; Raymond, Gary M; Butterworth, Erik et al. (2010) Multiscale modeling of metabolism, flows, and exchanges in heterogeneous organs. Ann N Y Acad Sci 1188:111-20
Bassingthwaighte, James B (2008) Linking cellular energetics to local flow regulation in the heart. Ann N Y Acad Sci 1123:126-33
Kellen, Michael R; Bassingthwaighte, James B (2003) Transient transcapillary exchange of water driven by osmotic forces in the heart. Am J Physiol Heart Circ Physiol 285:H1317-31
Bassingthwaighte, J B; Beard, D A; Li, Z (2001) The mechanical and metabolic basis of myocardial blood flow heterogeneity. Basic Res Cardiol 96:582-94
Schwartz, L M; Bukowski, T R; Ploger, J D et al. (2000) Endothelial adenosine transporter characterization in perfused guinea pig hearts. Am J Physiol Heart Circ Physiol 279:H1502-11
Schwartz, L M; Bukowski, T R; Revkin, J H et al. (1999) Cardiac endothelial transport and metabolism of adenosine and inosine. Am J Physiol 277:H1241-51
Bassingthwaighte, J B (1997) Design and strategy for the Cardionome Project. Adv Exp Med Biol 430:325-39
King, R B (1996) Modeling membrane transport. Adv Food Nutr Res 40:243-62
Stapleton, D D; Moffett, T C; Baskin, D G et al. (1995) Autoradiographic assessment of blood flow heterogeneity in the hamster heart. Microcirculation 2:277-82

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