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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.

Table 1

References

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    Pastor CM, et al.: . AJP 1999, in press.

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    Mehta S, et al.: . Crit Care Med 1999, 27: 385-393. 10.1097/00003246-199902000-00047

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    Santak B, et al.: . Br J Pharmacol 1998, 124: 1689-1697. 10.1038/sj.bjp.0701998

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    Mehta S, et al.: . Chest 1997, 111: 1045-1049.

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Acknowledgement

Supported by the Deutsche Forschungsgemeinschaft, Deutscher Akademischer Austauschdienst and ESICM.

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Theisen, M., Vasilev, D., Altherr, J. et al. Effect of iNOS inhibition on exhaled NO and serum nitrate in hyperdynamic porcine endotoxemia. Crit Care 4, P50 (2000). https://doi.org/10.1186/cc770

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Keywords

  • Nitric Oxide
  • iNOS Inhibition
  • Selective iNOS
  • Hepatic Venous
  • Plasma Nitrate