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

¹Departments of Mathematical Sciences and Biomedical Engineering, New Jersey Institute of Technology, Newark, New Jersey 07102; ²James Hogg iCAPTURE Centre, St. Paul's Hospital, University of British Columbia, Vancouver, British Columbia V6Z 1Y6; and ³Advanced Microvascular Imaging Laboratory, Lawson Health Research Institute and Department of Medical Biophysics, University of Western Ontario, London, Ontario, Canada N6A 5C1

Submitted 15 September 2003 ; accepted in final form 11 August 2004

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 (O₂), tissue PO₂ (P_t) 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 O₂ in AS and ES, respectively. Average (minimum) P_t 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 P_t 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 O₂ in sepsis expose skeletal muscle to significant regions of hypoxia, which could affect local cellular and organ function.

inflammation; computational model; microcirculation; spatial heterogeneity

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