Effect of sepsis on skeletal muscle oxygen consumption and tissue oxygenation: interpreting capillary oxygen transport data using a mathematical model.
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.
Dept. of Mathematical Sciences, New Jersey Institute of Technology, Univ. Heights, Newark, NJ 07102, USA. dgoldman@oak.njit.edu
Daniel
D
Goldman
Ryon M
RM
Bateman
Christopher G
CG
Ellis
D000818:Animals; D002196:Capillaries / Q000378:metabolism; D006801:Humans; D008955:Models, Cardiovascular; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption / Q000502:physiology*; D012039:Regional Blood Flow / Q000502:physiology; D018805:Sepsis / Q000378:metabolism* / Q000503:physiopathology*
D010100:Oxygen