Abstract | BACKGROUND: METHODS: Series 1: Sepsis was induced by cecal ligation and puncture (CLP). Animals received treatment of vehicle or sabiporide (10 mg/kg, p.o.). The experiment was terminated 20 h after CLP. Series 2: At 20 h after CLP, the necrotic cecum was excised and the abdominal cavity was washed. The animals were then returned to their cages. The experiment was terminated 7 d after CLP. RESULTS: Series 1: Compared with vehicle treatment, administration of sabiporide prevented hemodynamic derangement and improved cardiac function as evidenced by improved arterial pressure, left ventricle systolic pressure, ±dp/dt max, ejection fraction and fractional shorting, attenuated left ventricle end-diastolic pressure elevation, and wall motion abnormality. Furthermore, administration of sabiporide attenuated intestinal mucosal hyperpermeability and reduced accumulation of abdominal ascites. In addition, treatment with sabiporide also reduced plasma levels of tumor necrosis factor-α, interleukin 6, interleukin 10, cardiac troponin, aspartate aminotransferase, alanine aminotransferase, urea, and lactate, and attenuated neutrophil infiltration in the liver and gut. Series 2: Administration of sabiporide improved the 7-day survival rate after CLP in rats (42% in vehicle group versus 75% in sabiporide group). CONCLUSIONS: Administration of sabiporide improved cardiovascular performance, lessened the inflammatory response, tissue hypoperfusion and multiorgan injury, and most importantly reduced mortality.
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Authors | Xinchun Lin, Dongwon Lee, Dongmei Wu |
Journal | The Journal of surgical research
(J Surg Res)
Vol. 188
Issue 1
Pg. 231-7
(May 01 2014)
ISSN: 1095-8673 [Electronic] United States |
PMID | 24411641
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Copyright | Copyright © 2014 Elsevier Inc. All rights reserved. |
Chemical References |
- Biomarkers
- Guanidines
- Sodium-Hydrogen Exchangers
- sabiporide
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Topics |
- Animals
- Ascites
(prevention & control)
- Biomarkers
(blood)
- Cardiovascular Diseases
(etiology, prevention & control)
- Disease Models, Animal
- Drug Evaluation, Preclinical
- Guanidines
(pharmacology, therapeutic use)
- Heart
(drug effects)
- Hemodynamics
(drug effects)
- Intestinal Mucosa
(drug effects, metabolism)
- Male
- Multiple Organ Failure
(prevention & control)
- Permeability
(drug effects)
- Random Allocation
- Rats
- Rats, Sprague-Dawley
- Sepsis
(blood, complications, drug therapy)
- Sodium-Hydrogen Exchangers
(antagonists & inhibitors)
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