Methicillin-resistant Staphylococcus aureus-induced vascular leakage is associated with excessive production of nitric oxide and vascular endothelial growth factor
© BioMed Central Ltd 2007
Published: 26 September 2007
Methicillin-resistant Staphylococcus aureus (MRSA)-related pneumonia and/or sepsis are a frequent serious menace. The aim of the study was to establish a standardized and reproducible model of MRSA-related ovine septic pneumonia and to compare the pathophysiological responses to those seen in a previously established Pseudomonas aeruginosa-induced ovine sepsis model.
Materials and methods
Twenty-four sheep were operatively prepared for chronic study. After 5 days recovery, tracheostomy was performed under anesthesia and injury was given. Sheep were randomly allocated into four groups: (1) Sham group, no injury (n = 6); (2) Smoke group, exposed to smoke inhalation (n = 6); (3) PS group, exposed to smoke inhalation and instilled with P. aeruginosa (2.5 × 1011 CFU) into the lungs by bronchoscope (n = 6); and (4) MRSA group, exposed to smoke inhalation and instilled with MRSA (2.5 × 1011 CFU) into the lungs by bronchoscope (n = 6). Smoke inhalation injury was induced by inhalation of cotton smoke (48 breaths, <40°C). After the injury, animals were awakened and maintained on mechanical ventilation by 100% O2 for first 3 hours, and thereafter the O2 concentration was adjusted according to blood gases. The sheep, including the Sham group, were resuscitated by lactated Ringer's solution with an initial rate of 2 ml/kg/hour that was further adjusted according to hematocrit and filling pressure. The experiment lasted 24 hours.
Fluid net balance (ml/kg), 24 hours
-0.01 ± 6.0
12.7 ± 8.8
64.3 ± 14.8*†
167.0 ± 7.0*†#
Plasma nitrite/nitrate (μM), 24 hours
5.12 ± 0.7
4.85 ± 0.5
12.09 ± 0.7*†
22.3 ± 3.4*†#
The severe vascular leakage syndrome seen in the MRSA group may be due to excessive production of nitric oxide and vascular endothelial growth factor, a potent permeability factor. MRSA is largely responsible for these pathological changes rather than smoke inhalation alone.