A model for microcirculatory fluid and solute exchange in the heart
Kellen, Michael R., 1975-
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The exchange of fluids and solutes across the capillary wall is necessary to sustain multicellular life. Although the basic physiology of these processes is understood qualitatively, predicting the detailed kinetics of processes remains a challenge. An quantitatively precise understanding of the exchange process would benefit several practical application areas, including the optimization of drug delivery, engineering of new tissues, and understanding mechanisms of diseases including diabetes and cardiac edema.I have developed a quantitative model of microvascular exchange which includes a detailed description of the physical processes and anatomical structures involved in this process. Three features advance the model beyond previous work. First, my description of the transcapillary exchange process contains separate descriptions of coupled water and solute exchange through the endothelial junction, as well as a pathway for water exchange only across the endothelial cells. Treating each of these pathways individually provides a more accurate representation of the exchange process than models that lump different pathways into a single set of parameters. Second, an axially-distributed blood-tissue exchange region accounts for axial concentration gradients in the exchange region, and provides more accurate parameters estimates. Finally, the presence of a lymphatic drain in the interstitium permits net filtration across the capillary wall at steady-state, which is necessary to set the correct interstitial concentrations of chemical species.I have validated the model by comparison to osmotic weight transient experiments conducted in an isolated heart preparation. These experiments consist of the measurement of water fluxes across the capillary wall caused by changes in the solute concentration of the perfusate. Additionally, I have applied the model to two additional sets of experimental data: multiple indicator dilution curves, and lymph sampling methods. These methods provide independent and complementary information to my own data. The fact that a single model can be matched all of these diverse sets of data is powerful evidence that is the model is an accurate representation of the underlying physiology. The model therefore provides an integrative framework for understanding the microvascular exchange process.
- Bioengineering