Effect of iNOS inhibition on exhaled NO and serum nitrate in hyperdynamic porcine endotoxemia

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Introduction

Controversial data have been reported on the pivotal role of excessive nitric oxide (NO) production for sepsis-induced vasodilatation in higher species [1,2,3]. Since both the measurement of plasma nitrate (NO₃) and exhaled NO levels are used as a surrogate for excess NO formation, we investigated the effect of selective iNOS inhibition on these parameters during longterm porcine endotoxemia [4].

Methods

12 h after shock induction with continuous i.v. endotoxin (LPS) anesthetized pigs were randomly assigned to receive either LPS alone (CNT, n=13) or LPS plus the selective iNOS inhibitor 1400W (1400W, n=9) tritrated to keep MAP at pre-shock levels (range 0.1-0.5 mg/kg/h). Hydroethyl starch was infused to maintain sustained increase in cardiac output. Before, as well as 12, 18 and 24 h after, the start of LPS we measured expired NO levels and arterial (A), portal (PV) and hepatic venous (HV) NO₃ concentrations (after chemical reduction to NO) using chemiluminescence. Exhaled NO was calculated as described in [5].

Results

Data are median (25/75% quartiles), P<0.05 *vs pre-shock (RM ANOVA on ranks, SNK test for multiple comparison), ^†1400W vs CNT (Mann-Whitney Rank Sum Test). There was no significant relationship between exhaled NO and blood NO₃ concentration.

Conclusions

Remaining plasma NO₃ levels do not reflect excess NO release during sepsis, probably due to variable volume of distribution resulting from interstitial edema and/or flux into third spaces such as ascites. Exhaled NO may be more appropriate for on-line monitoring of NO production in sepsis.

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