The emphasis in the proposed program is on the elucidation of mechanisms of transport of small solutes from the blood into myocardial cells and on the evaluation of the characterizing transport rates across the capillary wall, via trans- or inter-endothelial cell routes through the interstitium and across the sarcolemma. Previous work has gone a long way in obtaining clear mathematical descriptions of intravascular transport; the proposed work puts a new emphasis on the mechanisms of capillary transport, particularly for fatty acids and substances which traverse the endothelial cells via facilitated or passive mechanisms. The work includes a sequence of studies designed to obtain more precise evaluations of transport of hydrophilic solutes across the capillary wall for a variety of sizes of probing molecules and to """"""""finally"""""""" resolve the disparities in estimates of capillary permeability by osmotic and tracer transient techniques. The multiple indicator dilution technique will be used to evaluate the unidirectional transsarcolemmal fluxes of glucoses and fatty acids. External detection approaches will be developed to refine the estimates of parameters. The program should produce and evaluate new techniques for estimating fluxes across cell walls in intact organs and provide data on specific solutes in the myocardium of dogs and rabbits. Data on metabolism obtained by tissue sampling techniques will be used in evaluating the ability to assess intracellular reactions from data on intact organs. Our goal is to demonstrate that in vivo organ metabolism can be explored by outflow or external detection.
| 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; Beard, Daniel A; Carlson, Brian E et al. (2012) Modeling to link regional myocardial work, metabolism and blood flows. Ann Biomed Eng 40:2379-98 |
| 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 |
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