Pulmonary vascular permeability changes in an ovine model of methicillin-resistant Staphylococcus aureus sepsis.
BACKGROUND
Endothelial dysfunction is a hallmark of sepsis, associated with lung transvascular fluid flux and pulmonary dysfunction in septic patients. We tested the hypothesis that methicillin-resistant Staphylococcus aureus (MRSA) sepsis following smoke inhalation increases pulmonary transvascular fluid flux via excessive nitric oxide (NO) production.


METHODS
Ewes were chronically instrumented, and randomised into either a control or MRSA sepsis (MRSA and smoke inhalation) group.


RESULTS
Pulmonary function remained stable in the control group, whereas the MRSA sepsis group developed impaired gas exchange and significantly increased lung lymph flow, permeability index and bloodless wet-to-dry weight-ratio (W/D ratio). The plasma nitrate/nitrite (NOx) levels, lung inducible nitric oxide synthases (iNOS) and endothelial nitric oxide synthases (eNOS), vascular endothelial growth factor (VEGF) protein expressions and poly-(ADP)-ribose (PAR) were significantly increased by MRSA challenge.


CONCLUSIONS
These results provide evidence that excessive NO production may mediate pulmonary vascular hyperpermeability in MRSA sepsis via up regulation of reactive radicals and VEGF.
Jonkam
Collette C
CC
Department of Anesthesiology, The University of Texas Medical Branch and Shriners Hospital for Children, Galveston, TX 77555-1102, USA. ccjonkam@utmb.edu
Bansal
Kamna
K
Traber
Daniel L
DL
Hamahata
Atsumori
A
Maybauer
Marc O
MO
Maybauer
Dirk M
DM
Cox
Robert A
RA
Lange
Matthias
M
Connelly
Rhykka L
RL
Traber
Lillian D
LD
Djukom
Clarisse D
CD
Salsbury
John R
JR
Herndon
David N
DN
Enkhbaatar
Perenlei
P
D000818:Animals; D002199:Capillary Permeability / Q000502:physiology*; D055370:Lung Injury / Q000378:metabolism* / Q000382:microbiology; D055624:Methicillin-Resistant Staphylococcus aureus / Q000378:metabolism*; D018805:Sepsis / Q000378:metabolism* / Q000382:microbiology; D034561:Sheep, Domestic; D013203:Staphylococcal Infections / Q000378:metabolism* / Q000382:microbiology