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Role of Nitric Oxide in an Ovine Model of Methicilin‐Resistant Staphylococcus aureus (MRSA) Sepsis
Author(s) -
Jonkam Collette,
Enkbaatar Perenlei,
Wang Jianpu,
Hamahata Atsumori,
Nakano Yoshimitsu,
Traber Lillian,
Herndon David,
Traber Daniel
Publication year - 2007
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.21.5.a524-a
Subject(s) - medicine , sepsis , nitric oxide , bolus (digestion) , staphylococcus aureus , vascular resistance , anesthesia , cardiac index , smoke inhalation injury , methicillin resistant staphylococcus aureus , hemodynamics , smoke inhalation , gastroenterology , inhalation , cardiac output , biology , bacteria , genetics
Over production of nitric oxide (NO) may play a central role in refractory hypotension and multiorgan dysfunction in MRSA sepsis. This study was designed to evaluate the role of NO in MRSA sepsis associated with smoke inhalation injury using L‐NAME (a nonspecific NOS inhibitor). METHODS: Sheep were surgically prepared and randomized to the groups: sham (non injured, non treated, n=6), control (injured, non treated, n=6) and L‐NAME (injured, treated with L‐NAME n=4). Injury was performed by insufflating 48 breaths of cotton smoke followed by instillation of 2–5 × 10^11 CFU of live MRSA into the airways of the sheep. L‐NAME (25mg/kg) was given as a bolus at 1h and 13h post injury. Results: Hemodynamic variables were stable in sham animals. Control sheep developed hyperdynamic sepsis as evidenced by a significant increase in cardiac index (CI)(BL: 6.2±0.3, 24h: 10.2±1.1) associated with severe drops in mean arterial pressure (MAP)(BL: 93.3±1.7, 24h: 65.0±5.3) and systemic vascular resistance index (SVRI)(BL: 1137.5±44.3, 24h: 419.1±71.1). L‐NAME stabilized the cardiovascular changes: CI (BL: 6.2±0.4, 24h: 6.3±0.4), MAP (BL: 102.5±3.5, 24h: 130.5±15.4) and SVRI (BL: 1254.2±123.0, 24h: 1156.2±88.7). Plasma nitrite/nitrate level increased 5‐fold 12h after injury and was significantly reduced by L‐NAME. Conclusion: NOS inhibition by L‐NAME reversed cardiovascular dysfunction, suggesting that excessive NO play a central role in MRSA‐induced cardiovascular collapse. For possible therapeutic intervention, effects of truly specific nitric oxide synthase inhibitors should be tested. Support: NIH GM066312 , SBI8450, 8820