Assessment of vascular permeability in an ovine model of acute lung injury and pneumonia-induced Pseudomonas aeruginosa sepsis.
OBJECTIVE
To assess the time changes and mechanism of pulmonary and peripheral vascular permeability in sheep with acute lung injury and sepsis.


METHODS
Prospective, controlled, randomized trial.


METHODS
University research laboratory.


METHODS
A total of 21 chronically instrumented, adult female sheep.


METHODS
Sheep were instrumented with lung and prefemoral lymph fistulas and allocated to either an uninjured control group (n = 5) or sepsis group (n = 5). The sheep in the sepsis group received cotton smoke inhalation injury followed by instillation of Pseudomonas aeruginosa into the lungs. All sheep were mechanically ventilated and fluid resuscitated for the entire duration of the 24-hr experiment. Additional sheep (n = 11) received injury and were killed at different time points for the measurement of vascular endothelial growth factor in lung tissue.


RESULTS
The injury induced a hypotensive-hyperdynamic circulation; increases in pulmonary capillary pressure, net fluid balance, lung and prefemoral lymph flow and protein content, lung water content, abdominal and thoracic fluid and protein content, neutrophil accumulation in the lung, and vascular endothelial growth factor expression in lung tissue; and decreases in PaO2/FiO2 ratio, plasma protein concentration, plasma oncotic pressure, and myocardial contractility.


CONCLUSIONS
Lung edema formation in this model was the result of marked increases in both pulmonary microvascular permeability and pressure. Pulmonary vascular hyperpermeability peaked 12 hrs postinjury and was related to vascular endothelial growth factor overexpression. Early myocardial failure was a potential contributor to the constant increase in pulmonary capillary pressure. The sepsis-induced increase in peripheral microvascular permeability was associated with significant accumulation of fluid and protein in the third space.
Lange
Matthias
M
Department of Anesthesiology, Investigational Intensive Care Unit, The University of Texas Medical Branch and Shriners Burns Hospital for Children, Galveston, TX, USA. lanm@gmx.de
Hamahata
Atsumori
A
Enkhbaatar
Perenlei
P
Esechie
Aimalohi
A
Connelly
Rhykka
R
Nakano
Yoshimitsu
Y
Jonkam
Collette
C
Cox
Robert A
RA
Traber
Lillian D
LD
Herndon
David N
DN
Traber
Daniel L
DL
D000818:Animals; D002199:Capillary Permeability; D004195:Disease Models, Animal; D005260:Female; D006439:Hemodynamics; D011550:Pseudomonas aeruginosa; D012128:Respiratory Distress Syndrome / Q000378:metabolism / Q000503:physiopathology*; D018805:Sepsis / Q000378:metabolism / Q000382:microbiology / Q000503:physiopathology*; D012756:Sheep; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D042461:Vascular Endothelial Growth Factor A