Abstract | BACKGROUND: METHODS: Anesthetized Wistar-Kyoto rats (250-300 g) underwent 40% blood volume hemorrhage over 10 minutes followed by 30 minutes of unresuscitated shock and were treated with either VPA (300 mg/kg) or vehicle control. Blood samples were obtained at baseline, after shock, and before death (at 1, 4, and 20 hours; n = 3-4/timepoint/group). Serum samples were screened for possible biomarkers using a multiplex electrochemiluminescence detection assay, and results were confirmed using enzyme-linked immunosorbent assay (ELISA). In addition, lung tissue lysate was examined for chemokine and myeloperoxidase (MPO) levels as a marker for neutrophil infiltration and ALI. Lung cytokine-induced neutrophil chemoattractant-1 (CINC-1; a chemokine belonging to the interleukin-8 family that promotes neutrophil chemotaxis) mRNA levels were measured by real-time polymerase chain reaction studies. RESULTS: Serum screening revealed that hemorrhage rapidly altered levels of circulating CINC-1. ELISA confirmed that CINC-1 protein was significantly elevated in the serum as early as 4 hours and in the lung at 20 hours after hemorrhage, without any significant changes in CINC-1 mRNA expression. Lung MPO levels were also elevated at both 4 and 20 hours after hemorrhage. VPA treatment attenuated these changes. CONCLUSION:
Hemorrhage resulted in the development of ALI, which was prevented with VPA treatment. Circulating CINC-1 levels rose rapidly after hemorrhage, and serum CINC-1 levels correlated with lung CINC-1 and MPO levels. This suggests that circulating CINC-1 levels could be used as an early marker for the subsequent development of organ inflammation and injury.
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Authors | Eugene Y Fukudome, Yongqing Li, Ashley R Kochanek, Jennifer Lu, Eleanor J Smith, Baoling Liu, Kyuseok Kim, George C Velmahos, Marc A deMoya, Hasan B Alam |
Journal | Surgery
(Surgery)
Vol. 152
Issue 2
Pg. 254-61
(Aug 2012)
ISSN: 1532-7361 [Electronic] United States |
PMID | 22657731
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Copyright | Copyright © 2012 Mosby, Inc. All rights reserved. |
Chemical References |
- Chemokine CXCL1
- Cxcl1 protein, rat
- Histone Deacetylase Inhibitors
- RNA, Messenger
- Valproic Acid
- Peroxidase
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Topics |
- Acute Lung Injury
(etiology, prevention & control)
- Animals
- Chemokine CXCL1
(blood)
- Histone Deacetylase Inhibitors
(therapeutic use)
- Lung
(enzymology)
- Peroxidase
(metabolism)
- RNA, Messenger
(metabolism)
- Rats
- Rats, Inbred WKY
- Resuscitation
- Shock, Hemorrhagic
(complications)
- Valproic Acid
(therapeutic use)
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