Effect of sepsis on skeletal muscle oxygen consumption and tissue oxygenation: interpreting capillary oxygen transport data using a mathematical model

Abstract

Inherent in the inflammatory response to sepsis is abnormal microvascular perfusion. Maldistribution of capillary red blood cell (RBC) flow in rat skeletal muscle has been characterized by increased 1) stopped-flow capillaries, 2) capillary oxygen extraction, and 3) ratio of fast-flow to normal-flow capillaries. On the basis of experimental data for functional capillary density (FCD), RBC velocity, and hemoglobin O2 saturation during sepsis, a mathematical model was used to calculate tissue O2 consumption (Vo2), tissue Po2 (Pt) profiles, and O2 delivery by fast-flow capillaries, which could not be measured experimentally. The model describes coupled capillary and tissue O2 transport using realistic blood and tissue biophysics and three-dimensional arrays of heterogeneously spaced capillaries and was solved numerically using a previously validated scheme. While total blood flow was maintained, capillary flow distribution was varied from 60/30/10% (normal/fast/stopped) in control to 33/33/33% (normal/fast/stopped) in average sepsis (AS) and 25/25/50% (normal/fast/stopped) in extreme sepsis (ES). Simulations found approximately two- and fourfold increases in tissue Vo2 in AS and ES, respectively. Average (minimum) Pt decreased from 43 (40) mmHg in control to 34 (27) and 26 (15) mmHg in AS and ES, respectively, and clustering fast-flow capillaries (increased flow heterogeneity) reduced minimum Pt to 14.5 mmHg. Thus, although fast capillaries prevented tissue dysoxia, they did not prevent increased hypoxia as the degree of microvascular injury increased. The model predicts that decreased FCD, increased fast flow, and increased Vo2 in sepsis expose skeletal muscle to significant regions of hypoxia, which could affect local cellular and organ function.

Divergent effects of low-O2tension and iloprost on ATP release from erythrocytes of humans with type 2 diabetes: implications for O2supply to skeletal muscle

“…Transport between the blood and tissue is described using a flux boundary condition with mass transfer coefficients calculated previously using a discrete erythrocyte model (7). For all O2 transport simulations, an array of 19 parallel capillaries was used to represent a typical capillary network (14,15) with the placement of capillaries and relative distribution of hemodynamic parameters (erythrocyte velocity and hematocrit) determined from in vivo measurements in the rat extensor digitorum longus muscle (8). The tissue domain surrounding the capillary array was 80 ϫ 331 ϫ 300 m. Capillary entrance saturations (71.5%) and the tissue O2 consumption rate (6.4 ϫ 10 Ϫ5 ml O2·ml…”

Evaluation of Vitamin C for Adjuvant Sepsis Therapy

“…The progression from infection to organ failure is precipitated by excessive accumulation of interstitial fluid (edema) and increased heterogeneity (maldistribution) of capillary blood flow, both of which lengthen the diffusion distance for oxygen and allow tissues to become hypoxic (23,34). The edema and blood flow maldistribution are consequences of capillary leakage and plugging, respectively.…”

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

“…The purpose of this paper is to extend a previously described mathematical/computational model (Goldman and Popel, 1999;Goldman and Popel, 2000;Goldman and Popel, 2001;Goldman et al, 2004;Popel et al, 2003) so that it can describe oxygen delivery to tissue in the presence and absence of plasma-based hemoglobin.. The current work modifies the original model by the addition of arterioles and venules to the geometric component and the addition of plasma hemoglobin to the blood flow and O 2 transport components.…”