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Capillary ischemia and abnormal capillary O2 flux during sepsis is not prevented by nitric oxide inhibition

Sepsis causes increased capillary stopped-flow, loss of capillary density, maldistribution of blood flow and increased oxygen extraction from 'normal' capillaries [1] in skeletal muscle. Since nitric oxide overproduction has been associated with refractory hypotension, capillary stopped-flow and decreased RBC deformability [2], we hypothesized that NO inhibition would prevent microvascular dysfunction. In a rat cecal ligation and perforation sepsis model, plasma NOx- level (NO chemiluminescence) was maintained at baseline by NO inhibition (L-NIL) and skeletal muscle capillary geometry, hemodynamics and RBC O2 saturation (SO2) were quantified (spectrophotometric functional imaging). O2 flux, amount of O2 leaving the capillary per unit surface area, was calculated from capillary dimensions and O2 flow rates. Sepsis increased plasma NOx- (145%), capillary stopped-flow (140%) and O2 flux (70%) and decreased MAP (30%) and RBC supply rate (SR) (25%) (P < 0.05). NO inhibition maintained RBC SR and partially maintained MAP (90% of base-line), but had no effect on capillary stopped-flow or O2 flux. We conclude that NO-independent capillary ischemia caused functional capillaries to off-load greater amounts of O2 to supply larger tissue volumes. Capillary SO2 < 8% indicated microvascular dysregulation and inefficient matching of local O2 delivery to local O2 demand. Improving capillary flow may benefit the septic patient.

References

  1. Ellis CG, Bateman RM, Sharpe MD, Sibbald WJ, Gill R: Effect of a maldistribution of microvascular blood flow on capillary O2extraction in sepsis. Am J Physiol Heart Circ Physiol 2002, 282: H156-H164.

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Bateman, R., Sharpe, M. & Ellis, C. Capillary ischemia and abnormal capillary O2 flux during sepsis is not prevented by nitric oxide inhibition. Crit Care 7, P051 (2003). https://doi.org/10.1186/cc1940

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  • DOI: https://doi.org/10.1186/cc1940

Keywords

  • Nitric Oxide
  • Supply Rate
  • Capillary Flow
  • Unit Surface Area
  • Microvascular Dysfunction