IN VITRO MODELS OF MICROCIRCULATION IN THE HUMAN FETUS, NEONATE AND ADULT

Abstract

Intravital studies on microcirculation in humans have been limited to superficial structures such as the skin or eye. We have used the lubrication theory to describe blood flow in capillaries with diameters of 3 to 6 μm. According to this model red blood cell (RBC) surface area and volume, plasma viscosity and capillary diameter determine the necessary driving pressure for a given RBC flow velocity, the intracapillary hematocrit and blood viscosity, and the critical capillary diameter for RBC passage. Plasma viscosity determines the friction in the gap between RBC and capillary wall (“lubrication”). Plasma viscosity (tube viscometer), surface area and volume of RBCs and the validity of the model (micropipette system) were studied using blood from 10 adults and cord blood from 10 fetuses (18-22 wk), 20 preterm (24-36 wk) and 10 full-term neonates. Results. Plasma viscosity increased with increasing maturity due to rising plasma protein concentrations. Volume and surface area of RBCs increased with increasing maturity. The flow model lead to the following conclusions: If the cells are suspended in the same medium, fetal and neonatal RBCs require 27% (term neonates) to 100% (fetuses) higher driving pressures than adult RBCs to achieve the necessary elongation for passing through a 4.5-μm capillary. However, the different RBCs require similar driving pressures if the cells are suspended in the corresponding autologous plasma. This suggests that the disadvantage of the large size of neonatal RBCs is compensated for by the low plasma viscosity. Blood viscosity is 9% (term neonates) to 29% (fetuses) less than in adults. Below a critical vessel diameter (3.3 μm for adults, 3.6 μm for full-term neonates, 3.8 μm for preterm infants, and 4.1 μm for fetuses), the driving pressure and blood viscosity increase steeply as a result of rising friction between RBC and vessel wall. Direct microscopic observation of RBCs flowing in pipettes with diameters of 3.5 and 4 um showed the validity of the model.