Blood flow, capillary transit times, and tissue oxygenation. The centennial of capillary recruitment.

The transport of oxygen between blood and tissue is limited by blood's capillary transit time: The time available for diffusion exchange before blood returns to the heart. If all capillaries had identical extraction properties, this physical limitation would render vasodilation and increased blood flow insufficient means to meet increased metabolic demands in the brain, heart, and other organs. In 1920, Danish physiologist August Krogh was awarded the Nobel Prize in Physiology or Medicine for his solution to this conceptual problem: Capillary recruitment, the opening of previously closed capillaries. Today, capillary recruitment mainly lives on i textbooks. When we suspect symptoms might represent hypoxia of a vascular origin, we search for relevant, flow-limiting conditions in our patients and rarely ascribe hypoxia or hypoxemia to short capillary transit times. This Primer describes how natural changes in capillary transit-time heterogeneity (CTH) and capillary hematocrit (across open capillaries) during increases in blood flow can match oxygen availability to metabolic demands in normal tissue, and how the assumption of negligible CTH lead us to underestimate capillaries' role in tissue oxygenation. CTH and capillary hematocrit depend on plasma viscosity, on the number, size and deformability of blood cells and their interactions with capillary endothelium, on the glycocalyx, endothelial cells, basement membrane, and pericytes that define the capillary lumen, and on any external compression. The Primer describes how risk factor- and disease-related changes in CTH and capillary hematocrit interfere with flow-metabolism coupling and tissue oxygenation, and discusses whether such capillary dysfunction contributes to vascular disease pathology.