Endothelial and coagulation dysfunction during porcine bacteremia: effects of combining iNOS inhibitor and radical scavenger

Introduction

We showed recently that both selective iNOS inhibition and the radical scavenger Tempol prevented live bacteria from causing key features of hemodynamic, microcirculatory and metabolic derangements in porcine sepsis [1, 2]. Here we investigated the effects of combined selective iNOS inhibition (L-NIL) with a free radical scavenger (Tempol) on P. aeruginosa-induced endothelial and hemostatic stress.

Methods

Twelve hours after induction of sepsis with continuous i.v. P. aeruginosa, 16 pigs received either no drug (CONT, n = 8) or a combination of L-NIL + Tempol (COMB, n = 8). Before and 12, 18 and 24 hours after the start of P. aeruginosa, plasma levels of markers related to endothelial function (von Willebrand factor [vWf]), hypercoagulability (thrombin-antithrombin complexes [TAT]), oxidative stress (8-isoprostane) and inflammation (TNF-α) were assessed.

Results

See Table 1. Combined treatment prevented a sepsis-induced increase in plasma 8-isoprostane and substantially attenuated the gradual increase in TNF-α.

Table 1

Conclusion

Live bacteria-induced sepsis resulted in endothelial activation/dysfunction associated with activated coagulation, which were markedly attenuated by the combined iNOS blockade and radical scavenging. Suppression of oxidative stress and excessive inflammation might contribute to these results.