Nitric oxide prevents the bacterial translocation and inhibits the systemic inflammatory response produced by implantation of a vascular prosthesis followed by Zymosan A

Abstract.

Objective and design: To evaluate the beneficial effects of exogenous NO and its levels of action in a model of SIRS/Bacterial Translocation (BT) induced by two sequential insults.

Material or subjects: Eighty-six Wistar rats were submitted to different treatments and their tissue and blood samples were accessed at the end of the experiment.

Treatment: Nitric Oxide was compared to Gentamicin as the tested guideline for our study.

Methods: Dacron graft implantation (first insult) and subsequent administration of Zymosan A^® (second insult) were performed in Wistar rats. The animals were divided into 6 groups: I) No manipulation (BASAL); II) Laparotomy (L) + mineral oil (SHAM); III) L + Graft-Zymosan (GZ) (CONTROL); IV) L + GZ + Antibiotic (A) (ASSAY I); V) L + GZ + NO (ASSAY II) and VI) L + GZ + A + NO (ASSAY III). Determinations: Survival, Bacterial Translocation, myeloperoxidase (MPO), Cytokines (TNF-α, IL-1β, IFN-γ), Oxygen Free Radical (OFR) SOA and detoxifying enzymes (SOD, Superoxide Dismutase, CAT, Catalase and GPX, Glutathione Peroxidase), Cell Adhesion Molecules, CAMs (ICAM-1, VCAM-1 and PECAM-1) and Nuclear Transcription Factor, NFκB.

Results: The model established induced a mortality rate of 20% and generated BT in all samples. It also significantly increased all variables, with P < 0.001 for MPO and all Cytokines; P < 0.01 for all OFR, and P < 0.05 for CAMs and for NFκB. Treatment with A reduced mortality to 0%, significantly decreased BT, MPO, Cytokines and OFR (P < 0.05), but did not reduce CAMs or NFκB. NO, either alone or associated, reduced mortality to 0% and abolished BT, significantly decreasing nearly all the variables studied (P < 0.001 for MPO and all Cytokines; P < 0.01 for OFR, and P < 0.05 for CAMs and for NFκB).

Conclusions: The exogenous administration of NO before the two sequential insults prevented BT and controlled SIRS peripherally and at both cellular and transcriptional level in a lasting manner. In contrast, antibiotic treatment only exerted its action at peripheral level. The association of both treatments did not provide any important advantages.