Quantitative knowledge of microcirculatory blood ow, molecular transport, and their regulation has been accumulated primarily in the past 40 years owing to signicant innovations in methods and techniques to measure microcirculatory parameters and analyze microcirculatory data. e development of these methods has required joint eorts of physiologists and biomedical engineers. Key innovations include signicant improvements in intravital microscopy, the dual-slit method (WaylandJohnson) for measuring velocity in microvessels, the servo-null method (Wiederhielm-Intaglietta) for measuring pressure in microvessels, the recessed oxygen microelectrode (Whalen) for polarographic measurements of partial pressure of oxygen, and the microspectrophotometric method (PittmanDuling) for measuring oxyhemoglobin saturation in microvessels. e single-capillary cannulation method (Landis-Michel) has provided a powerful tool for studies of transport of water and solutes through the capillary endothelium. New experimental techniques have appeared, many adapted from cell biology and modied for in vivo studies, that are having a tremendous impact on the eld. Examples include confocal and multiphoton microscopy for better three-dimensional resolution of microvascular structures, methods of optical imaging using uorescent labels (e.g., labeling blood cells for velocity measurements), uorescent dyes (e.g., calcium ion and nitric oxide sensitive dyes for measuring their dynamics in vascular smooth muscle, endothelium, and surrounding tissue cells in vivo), and quantum dots, development of sensors (glass laments, optical and magnetic tweezers, atomic force microscopy (AFM)) for measuring forces in the nanonewton to piconewton range that are characteristic of cell-cell and molecular interactions, phosphorescence decay measurements as an indicator of oxygen tension and oxygen consumption, and methods of manipulating receptors on the surfaces of blood cells and endothelial cells. In addition to the dramatic developments in experimental techniques, quantitative knowledge and understanding of the microcirculation have been signicantly enhanced by theoretical studies, perhaps having a larger impact than in other areas of physiology. Extensive theoretical work has been conducted on the mechanics of the red blood cell (RBC) and leukocyte, from the molecular to the cellular levels, mechanics of blood ow in single microvessels and microvascular networks, oxygen (O2), carbon dioxide (CO2), and nitric oxide (NO) exchange between microvessels and surrounding tissue, and water and solute transport through capillary endothelium and the surrounding tissue . ese theoretical studies not only aid in the interpretation of experimental data but in many cases also serve as a framework for quantitative testing of working hypotheses and as a guide in designing and conducting further experiments. e accumulated knowledge has led to signicant progress in our understanding of mechanisms of regulation of blood ow and molecular exchange in the microcirculation in many organs and tissues under a variety of physiological and pathological conditions (e.g., hypoxia, hypertension, sickle cell anemia, diabetes, inammation, hemorrhage, ischemia/reperfusion, sepsis, and cancer).
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)