Whitaker Lecture 1996: microcirculation, biomedical engineering, and artificial blood.

The development of artificial blood requires the understanding of how blood behaves at the level of the microcirculation. A number of measuring systems have recently become available that allow analysis of the transport properties of blood and the microvessels in terms of pressure, flow, the dynamics of their diameter changes, and the rate and manner of oxygen delivery. Findings from this technology have led to the development of an analytical framework with which to assess the consequences of altering the physical properties of blood and to verify quantitatively theoretical predictions. Results show that blood viscosity and oxygen-carrying capacity are directly related, and must be jointly modified in a prescribed manner to maintain tissue oxygen delivery. The use of optical techniques to assess flow and oxygen delivery in experimental animal models show that the consumption of oxygen by the microvessel wall is an important determinant of tissue oxygenation. Furthermore, the viscosity of blood and/or the mixture of blood and an artificial substitute must achieve a viscosity that is close to normal. Low blood viscosity is not necessarily beneficial, unless blood flow velocity rises to maintain the shear stress at the wall needed for the generation of local vasodilators. Manipulating physical properties of currently available modified hemoglobins by mixing them with conventional plasma expanders yield fluids that may provide optimal blood replacements.