Cardiovascular collapse and vascular permeability changes in an ovine model of methicillin-resistant Staphylococcus aureus sepsis.
Methicillin-resistant Staphylococcus aureus (MRSA) infections with severe outcomes such as sepsis and septic shock are progressively increasing in both the community and in hospital settings. We hypothesized that overexpression of reactive nitrogen and oxygen species and vascular endothelial growth factor (VEGF) play a pivotal role in cardiovascular collapse associated with vascular hyperpermeability in MRSA sepsis. Twelve sheep were surgically prepared and randomized into a control (noninjured; n = 6) and a sepsis (injured; n = 6) group. Animals in the sepsis group were subjected to cotton smoke inhalation and instillation of 2.5 x 10(11) colony-forming units of live MRSA into both lungs. Cardiovascular variables in the control group remained stable, whereas the MRSA sepsis group developed a hypotensive and hyperdynamic circulatory shock state beginning at 6 h associated with significantly increased vascular permeability evidenced by increased prefemoral lymph flow starting at 12 h and permeability index from 12 to 18 h, higher fluid accumulation from 12 to 24 h, and significantly decreased plasma protein concentration and oncotic pressure beginning at 6 h compared with control animals. Myocardial 3-nitrotyrosine (3-NT) protein, poly (adenosine diphosphate-ribose), and VEGF mRNA expressions measured after the 24-h experiment were significantly increased in the injured animals as well. These results evidence that excessive production of reactive radicals and VEGF may play a major role in cardiovascular collapse and vascular hyperpermeability in MRSA sepsis.
Jonkam
Collette C
CC
Department of Anesthesiology, The University of Texas Medical Branch and Shriners Hospital for Children, Galveston, Texas, USA. ccjonkam@utmb.edu
Lange
Matthias
M
Traber
Daniel L
DL
Maybauer
Dirk M
DM
Maybauer
Marc O
MO
Bansal
Kamna
K
Hamahata
Atsumori
A
Zhu
Yong
Y
Esechie
Aimalohi
A
Traber
Lillian D
LD
Sousse
Linda
L
Rehberg
Sebastian
S
Herndon
David N
DN
Enkhbaatar
Perenlei
P
D000818:Animals; D002199:Capillary Permeability; D002319:Cardiovascular System / Q000293:injuries; D024881:Drug Resistance, Bacterial; D005609:Free Radicals; D006321:Heart / Q000382:microbiology; D008168:Lung / Q000382:microbiology; D008712:Methicillin / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D018805:Sepsis / Q000382:microbiology* / Q000503:physiopathology*; D034561:Sheep, Domestic; D012772:Shock, Septic / Q000503:physiopathology; D013211:Staphylococcus aureus / Q000378:metabolism*; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D005609:Free Radicals; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D008712:Methicillin