Whole Organ Approaches to Cellular Metabolism

Knowledge of how living organisms function is the province of physiology. This book takes on the challenge of summarizing our knowledge of processes that take place at microscopic levels in cells and tissues, but using physiological methods that involve whole organs, where physiological phenomena are measured differently than at cellular and subcellular scales.

The field of capillary-tissue exchange physiology has been galvanized twice in the past 25 years. A 1969 conference at the National Academy of Sciences in Copenhagen resulted in the book Capillary Permeability: The Transfer of Mole cules and Ions Between the Capillary Blood and the Tissue (Crone and Lassen, 1970). It focused on the physiochemical aspects of transcapillary water and solute transport. The field has matured considerably since. This volume was designed as the successor to the 1970 book, and was created at a gathering of the authors at McGill University. It too captures the breadth of a field that has been dramatically enriched by numerous technical and conceptual advances. In 1970 it was already known that the capillary wall was not merely a "cellophane bag" exerting steric hindrances on solute particles. Instead, the endothelial surface was recognized as the site of binding reactions and permeation by passive or carrier-mediated trans port. Furthermore, the cells of the blood could traverse evanescent wide openings in the "zippered" clefts. Today, research priorities have turned more to cell-cell interactions, toward understanding the utility of the gap junctional connections between endothelial cells and neighboring smooth muscle cells, neuronal twigs, and the parenchymal cells of organs. New discoveries in the past few years have revealed the critical importance of the close relationships between the endothelial cells and the parenchymal cells.

Knowledge of how living organisms function is the province of physiology. This book takes on the challenge of summarizing our knowledge of processes that take place at microscopic levels in cells and tissues, but using physiological methods that involve whole organs, where physiological phenomena are measured differently than at cellular and subcellular scales.

1. Introduction.- 1. Modeling in the Analysis of the Processes of Uptake and Metabolism in the Whole Organ.- 2. Mechanisms of Endothelial Transport, Exchange, and Regulation.- 2. Transport Functions of the Glycocalyx, Specific Proteins, and Caveolae in Endothelium.- 3. Study of Blood Capillary Permeability with the Rete Mirabile.- 4. Interactions Between Bovine Adrenal Medulla Endothelial and Chromaffin Cells.- 5. Studies of the Glomerular Filtration Barrier: Integration of Physiologic and Cell Biologic Experimental Approaches.- 6. Endothelial Barrier Dynamics: Studies in a Cell-Column Model of the Microvasculature.- 3. Metabolism in the Heart and Skeletal Muscle.- 7. Strategies for Uncovering the Kinetics of Nucleoside Transport and Metabolism in Capillary Endothelial Cells.- 8. Norepinephrine Kinetics in Normal and Failing Myocardium: The Importance of Distributed Modeling.- 9. Metabolic Response Times: A Generalization of Indicator Dilution Theory Applied to Cardiac O2 Consumption Transients.- 10. Quantitative Assessment of Sites of Adenosine Production in the Heart.- 11. Role of Capillary Endothelial Cells in Transport and Metabolism of Adenosine in the Heart: An Example of the Impact of Endothelial Cells on Measures of Metabolism.- 12. Distribution of Intravascular and Extravascular Resistances to Oxygen Transport.- 4. Metabolism in the Liver.- 13. Liver Cell Entry In Vivo and Enzymic Conversion.- 14. Probing the Structure and Function of the Liver with the Multiple-Indicator Dilution Technique.- 15. A Generalized Mathematical Theory of the Multiple-Indicator Dilution Method.- 16. Impact of Extracellular and Intracellular Diffusion on Hepatic Uptake Kinetics.- 5. Metabolism in the Lung.- 17. The Uptake and Metabolism of Substrates by Endothelium in the Lung.- 18. Pulmonary Endothelial Surface Reductase Kinetics.- 19. Water and Small Solute Exchanges in the Lungs.- 20. Pulmonary Perfusion and the Exchange of Water and Acid in the Lungs.- 21. The Transport of Small Molecules Across the Microvascular Barrier as a Measure of Permeability and Functioning Exchange Area in the Normal and Acutely Injured Lung.- 22. Lipophilic Amines as Probes for Measurement of Lung Capillary Transport Function and Tissue Composition Using the Multiple-Indicator Dilution Method.- Publications of Carl A. Goresky.