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Role of Inducible Nitric Oxide Synthase In Septic Shock
Author(s) -
Enkhbaatar Perenlei,
Cox R,
Traber LD,
Maybauer MO,
Maybauer DM,
Nakano YY,
Hawkins H,
Schmalstieg F,
Herndon D,
Traber DL
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1391
Pneumonia and/or sepsis increase mortality of burn victims. It is reported that nitric oxide plays a major role in pathogenesis of sepsis. However, there is a question as to which of the three isoforms of nitric oxide synthase (NOS) are involved in pathological lesions of sepsis. To shed some light on this issue, we tested effect of a highly selective NOS‐2 inhibitor on ovine model of septic shock. Method After recovery from operative preparation (7 d), sheep were anesthetized, insufflated with cotton smoke and Ps. aeruginosa (5X10 11 CFU) in the lung through a tracheostomy. Sheep were ventilated for 24h and equally resuscitated. Animal grouping: sham, (no injury, no treatment, n=6); injured (injured, not‐treated, n=6); treated, injured treated with iNOS inhibitor, BBS‐2 (100ug/kg/h, iv., 1h post‐injury, n=6). Results Cardiopulmonary variables were stable in sham animals. In injured untreated animals PaO 2 /FiO 2 fell, pulmonary shunt fraction rose, lung water content (W/D), airway obstruction (AO) lung inflammation (LI), and plasma nitrite/nitrate (NOx) increased. Treatment with NOS‐2 (1h post injury) significantly attenuated all these changes except lung water content. The fall in arterial pressure (MAP) and systemic vascular resistance (SVRI, dyn.s.cm −5 .m −2 ) was not affected by iNOS inhibition (Table 1).Conclusion iNOS is only partially responsible for the cardiopulmonary lesions of sepsis in this clinically relevant ovine model. *p<0.05 vs. injured (I). T, treated. Support: RO1GM060688, CON14589 (AHA)