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.