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


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


METHODS
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((R)) (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-alpha, IL-1beta, IFN-gamma), 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, NFkappaB.


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 NFkappaB. Treatment with A reduced mortality to 0%, significantly decreased BT, MPO, Cytokines and OFR (P < 0.05), but did not reduce CAMs or NFkappaB. 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 NFkappaB).


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.
Departamento de Cirugía, Facultad de Medicina. Avda. Alfonso X El Sabio s/n, 37007, Salamanca, Spain. marcellobb@bol.com.br
F S
FS
Lozano
M B
MB
Barros
M J
MJ
Fresnadillo
F J
FJ
García-Criado
A
A
Gomez-Alonso
D000818:Animals; D018988:Bacterial Translocation / Q000187:drug effects*; D001807:Blood Vessel Prosthesis / Q000009:adverse effects*; D002374:Catalase / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D007150:Immunohistochemistry; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000382:microbiology / Q000517:prevention & control*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D015996:Survival Rate; D015054:Zymosan / Q000494:pharmacology*
D016207:Cytokines; D005609:Free Radicals; D016328:NF-kappa B; D009569:Nitric Oxide; D015054:Zymosan; D002374:Catalase; D009195:Peroxidase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase