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Loss of erythrocyte deformability during systemic sepsis is prevented by nitric oxide synthase inhibition

Introduction

`Rigid' red cells in sepsis are thought to play a role in multiorgan failure by plugging the microvasculature and compromising oxygen delivery. During sepsis endogenous nitric oxide (NO) production is increased. What effect this has on erythrocyte deformability (RBCd) is unclear. We report the effects on RBCd and capillary blood flow when NO overproduction was prevented in septic rats.

Methods

Acute sepsis was induced in Sprague-Dawley rats via cecal ligation and perforation (CLP). At 2 h post CLP, amino-guanidine (AG), a selective inducible nitric oxide synthase inhibitor was infused (i.v. 60 mg/kg/h) to maintain baseline NOx levels. Capillary blood flow in the EDL skeletal muscle was filmed using intravital video microscopy. Plasma Nox (NO2 -/NO3 -) levels were measured by chemiluminescence and deformability was assessed by membrane displacement, using the micropipette aspiration technique.

Results

At 6 h, an increase in plasma NOx of 260% ± 46 SEM in CLP animals was associated with a 12% ± 1.6 SEM loss in red cell deformability and a twofold increase in stopped flow capillaries (P < 0.05, relative to Sham). Infusion of AG prevented the increase in NOx, the loss of deformability and the increase in stopped capillary flow, (P < 0.05). In sham rats, AG augmented RBCd (P < 0.05), but had no effect on stopped flow.

Conclusion

Eliminating nitric oxide overproduction in septic rats was associated with preventing 1) the loss of red cell deformability and 2) the increase in stopped capillary blood flow, resulting in the maintenance of the microvascular circulation.

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Bateman, R., Jagger, J., Sharpe, M. et al. Loss of erythrocyte deformability during systemic sepsis is prevented by nitric oxide synthase inhibition. Crit Care 3, P074 (2000). https://doi.org/10.1186/cc449

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Keywords

  • Nitric Oxide
  • Capillary Blood Flow
  • Erythrocyte Deformability
  • Endogenous Nitric Oxide
  • Micropipette Aspiration