A computational model of oxygen delivery by hemoglobin-based oxygen carriers in three-dimensional microvascular networks

Abstract

A detailed computational model is developed to simulate oxygen transport from a three-dimensional microvascular network to surrounding tissue in the presence of hemoglobin-based oxygen carriers. The model accounts for nonlinear O 2 consumption, myoglobin facilitated diffusion and nonlinear oxyhemoglobin dissociation in the RBCs and plasma. It also includes a detailed description of intravascular resistance to O 2 transport and is capable of incorporating realistic three-dimensional microvascular network geometries. Simulations in this study were performed using a computergenerated microvascular architecture that mimics morphometric parameters for the hamster cheek pouch retractor muscle. Theoretical results are presented next to corresponding experimental data. Phosphoresence quenching microscopy provided PO 2 measurements at the arteriolar and venular ends of capillaries in the hamster retractor muscle before and after isovolemic hemodilution with three different hemodilutents; a non-oxygen-carrying plasma expander and two hemoglobin solutions with different oxygen affinities. Sample results in a microvascular network show an enhancement of diffusive shunting between arterioles, venules and capillaries and a decrease in hemoglobin's effectiveness for tissue oxygenation when its affinity for O 2 is decreased. Model simulations suggest that microvascular network anatomy can affect the optimal hemoglobin affinity for reducing tissue hypoxia. O 2 transport simulations in realistic representations of microvascular networks should provide a theoretical framework for choosing optimal parameter values in the development of hemoglobin-based blood-substitutes.

The capillary bed offers the largest hemodynamic resistance to the cortical blood supply

“…Furthermore, non-linear oxygen-hemoglobin dissociation kinetics 37,54,66,67 from the erythrocytes to plasma were implemented. The rate of oxygen desaturation from hemoglobin to plasma, _ R R!P , in equation (3) was given by a first-order kinetic rate law, described in equations (13) to (15) of Supplemental Information, where additional details on the full binding kinetics are provided. It is important to note that the proposed oxygen dissociation kinetics obeys to the well-known Hill equation when reaching equilibrium.…”

Vascular Graph Model to Simulate the Cerebral Blood Flow in Realistic Vascular Networks

“…The more general models that have been introduced, either make highly simplified approximations of the angioarchitecture or focus on a small fraction of the cerebral vasculature only, for example, the microvascular network (Tsoukias et al, 2007) or large vascular structures, such as the Circle of Willis (Castro et al, 2006). Boas et al have recently presented a framework that is restricted neither to a specific imaging method nor to a particular fraction of the vasculature .…”

Quantification of the effects of vasomotion on mass transport to tissue from axisymmetric blood vessels

“…amongst others, Goldman et al, 2001, andTsoukias et al, 2007. The former found that at physiological levels of tissue myoglobin vasomotion did not improve tissue oxygenation (but did so under other conditions).…”