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This Article Full Text Full Text (PDF) All Versions of this Article: 290/6/H2277    most recent 00547.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (11) Citing Articles via Google Scholar Google Scholar Articles by Goldman, D. Articles by Ellis, C. G. Search for Related Content PubMed PubMed Citation Articles by Goldman, D. Articles by Ellis, C. G.

Effect of decreased O₂ supply on skeletal muscle oxygenation and O₂ consumption during sepsis: role of heterogeneous capillary spacing and blood flow

¹Departments of Mathematical Sciences and Biomedical Engineering, New Jersey Institute of Technology, Newark, New Jersey; ²iCAPTURE Centre, University of British Columbia, Vancouver, British Columbia; and ³Department of Medical Biophysics, University of Western Ontario, London, Ontario, Canada

Submitted 24 May 2005 ; accepted in final form 23 December 2005

One of the main aspects of the initial phase of the septic inflammatory response to a bacterial infection is abnormal microvascular perfusion, including decreased functional capillary density (FCD) and increased blood flow heterogeneity. On the other hand, one of the most important phenomena observed in the later stages of sepsis is an increased dependence of tissue O₂ utilization on the convective O₂ supply. This "pathological supply dependency" is associated with organ failure and poor clinical outcomes. Here, a detailed theoretical model of capillary-to-tissue O₂ transport during sepsis is used to examine the origins of abnormal supply dependency. With use of three-dimensional arrays of capillaries with heterogeneous spacing and blood flow, steady-state O₂ transport is simulated numerically during reductions in the O₂ supply. Increased supply dependency is shown to occur in sepsis for hypoxic (decreased hemoglobin O₂ saturation) and stagnant (decreased blood flow) hypoxia. For stagnant hypoxia, a reduction in FCD with decreasing blood flow is necessary to obtain the observed increase in supply dependency. Our results imply that supply dependency observed under normal conditions does not have its origin at the level of individual capillaries. In sepsis, however, diffusion limitation and shunting of O₂ by individual capillaries occur to a degree that is dependent on the heterogeneity of septic injury and the arrangement of capillary networks. Thus heterogeneous stoppage of individual capillaries is a likely factor in pathological supply dependency.

inflammation; computational model; microcirculation; supply dependency; functional shunting

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