The endothelial lining of blood vessels presents a large surface area for exchange of materials between blood and tissues, and is critically involved in many other processes such as regulation of blood flow, inflammatory responses and blood coagulation. It has long been known that the luminal surface of the endothelium is lined with a glycocalyx, a layer of membrane-bound macromolecules which has been determined by electron microscopy to be several tens of nanometers thick. However, investigations in vivo have indicated the presence of a much thicker endothelial surface layer (ESL), with an estimated thickness ranging from 0.5 microm to over 1 microm, that restricts the flow of plasma and can exclude red blood cells and some macromolecular solutes. The evidence for the existence of the ESL, hypotheses about its composition and biophysical properties, its relevance to physiological processes, and its possible clinical implications are considered in this review.

Since the original publications by Martini et al. (Dtsch. Arch. Klin. Med. 169: 212-222, 1930) and Fahraeus and Lindqvist (Am. J. Physiol. 96: 562-568, 1931), it has been known that the relative apparent viscosity of blood in tube flow depends on tube diameter. Quantitative descriptions of this effect and of the dependence of blood viscosity on hematocrit in the different diameter tubes are required for the development of hydrodynamic models of blood flow through the microcirculation. The present study provides a comprehensive data base for the description of relative apparent blood viscosity as a function of tube diameter and hematocrit. Data available from the literature are compiled, and new experimental data obtained in a capillary viscometer are presented. The combined data base comprises measurements at high shear rates (u > or = 50 s-1) in tubes with diameters ranging from 3.3 to 1,978 microns at hematocrits of up to 0.9. If corrected for differences in suspending medium viscosity and temperature, the data show remarkable agreement. Empirical fitting equations predicting relative apparent blood viscosity from tube diameter and hematocrit are presented. A pronounced change in the hematocrit dependence of relative viscosity is observed in a range of tube diameters in which viscosity is minimal. While a linear hematocrit-viscosity relationship is found in tubes of < or = 6 microns, an overproportional increase of viscosity with hematocrit prevails in tubes of > or = 9 microns. This is interpreted to reflect the hematocrit-dependent transition from single- to multifile arrangement of cells in flow.

A theoretical model has been developed to simulate blood flow through large microcirculatory networks. The model takes into account the dependence of apparent viscosity of blood on vessel diameter and hematocrit (the Fahraeus-Lindqvist effect), the reduction of intravascular hematocrit relative to the inflow hematocrit of a vessel (the Fahraeus effect), and the disproportionate distribution of red blood cells and plasma at arteriolar bifurcations (phase separation). The model was used to simulate flow in three microvascular networks in the rat mesentery with 436,583, and 913 vessel segments, respectively, using experimental data (length, diameter, and topological organization) obtained from the same networks. Measurements of hematocrit and flow direction in all vessel segments of these networks tested the validity of model results. These tests demonstrate that the prediction of parameters for individual vessel segments in large networks exhibits a high degree of uncertainty; for example, the squared coefficient of correlation between predicted and measured hematocrit of single vessel segments ranges only between 0.15 and 0.33. In contrast, the simulation of integrated characteristics of the network hemodynamics, such as the mean segment hematocrit or the distribution of blood flow velocities, is very precise. In addition, the following conclusions were derived from the comparison of predicted and measured values: 1) The low capillary hematocrits found in mesenteric microcirculatory networks as well as their heterogeneity can be explained on the basis of the Fahraeus effect and phase-separation phenomena. 2) The apparent viscosity of blood in vessels of the investigated tissue with diameters less than 15 microns is substantially higher than expected compared with measurements in glass tubes with the same diameter.

Resistance to blood flow through peripheral vascular beds strongly influences cardiovascular function and transport to tissue. For a given vascular architecture, flow resistance is determined by the rheological behavior of blood flowing through microvessels. A new approach for calculating the contribution of blood rheology to microvascular flow resistance is presented. Morphology (diameter and length), flow velocity, hematocrit, and topological position were determined for all vessel segments (up to 913) of terminal microcirculatory networks in the rat mesentery by intravital microscopy. Flow velocity and hematocrit were also predicted from mathematical flow simulations, in which the assumed dependence of flow resistance on diameter, hematocrit, and shear rate was optimized to minimize the deviation between measured and predicted values. For microvessels with diameters below %z40 ,um, the resulting flow resistances are markedly higher and show a stronger dependence on hematocrit than previously estimated from measurements of blood flow in narrow glass tubes. For example, flow resistance in 10-am microvessels at normal hematocrit is found to exceed that of a corresponding glass tube by a factor of =4. In separate experiments, flow resistance of microvascular networks was estimated from direct measurements of total pressure drop and volume flow, at systemic hematocrits intentionally varied from 0.08 to 0.68. The results agree closely with predictions based on the above-optimized resistance but not with predictions based on glass-tube data. The unexpectedly high flow resistance in small microvessels may be related to interactions between blood components and the inner vessel surface that do not occur in smooth-walled tubes. (Circ Res. 1994;75: 904-915.) Key Words * blood viscosity * peripheral resistancemicrovascular networks * pressure drop * hematocrit E arly in the 19th century direct measurements of arterial and venous blood pressure by Jean Leonard Marie Poiseuille12 revealed that the pressure drop in the circulation occurs mainly in the peripheral vascular bed (the microcirculation), which consists of large numbers of tiny vessels. The microcirculation is therefore the site of most of the resistance to flow, which depends on the architecture of the microvascular network and on the rheological behavior of blood flowing through it. Information about bulk rheological properties of blood has been obtained using rotational viscometers. The findings of such studies, including the nonlinear increase of viscosity with increasing hematocrit and with decreasing shear rate,3-5 have strongly influenced the interpretation of physiological and pathophysiological behavior of the peripheral circulation.However, knowledge of the bulk material properties of blood does not provide a sufficient basis for understanding blood flow through narrow cylindrical tubes. In tubes with diameters >1 mm, the measured apparent viscosities correspond to bulk values from rotational viscometry, but a marked reduction of viscosity is...

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