Document Detail

Endothelin receptor antagonist attenuates inflammatory response and prolongs the survival time in a neonatal sepsis model.
MedLine Citation:
PMID:  20845025     Owner:  NLM     Status:  In-Process    
PURPOSE: To evaluate effects of endothelin receptor antagonist ETR-P1/fl in a neonatal sepsis model.
METHOD: Eighteen anesthetized and mechanically ventilated 3-day-old piglets were divided into three groups. Six piglets received cecal ligation and perforation (CLP group). Six piglets were administrated a continuous infusion of ETR-P1/fl (0.05 mg/kg/h), an antisense homology box-derived peptide with an endothelin A receptor antagonist effect, starting 30 min after CLP (ETR-P1/fl group). Six piglets acted as the sham group. Mean arterial pressure (MAP), heart rate, cardiac output, arterial blood gas, body temp (BT), serum nitrite and nitrate (NOx), tumor necrosis factor (TNF)-α, and high-mobility group box 1 (HMGB-1) were measured before CLP and at 1, 3, 6, and 9 h after CLP.
RESULTS: Cecal ligation and perforation exposure evoked a state of shock and showed deteriorated cardiac output, pulmonary hypertension, decreased MAP, low oxygen saturation, and base excess (BE) with elevated TNF-α, NOx, and HMGB1. ETR-P1/fl administration resulted in higher MAP at 6 and 9 h after CLP, less negative BE, lower mean pulmonary arterial pressure (mPAP)/MAP ratio at 9 h after CLP, and lower TNF-α, NOx, and HMGB-1 compared to the CLP group. BT showed no differences between the groups. Survival time in the ETR-P1/fl group was longer than in the CLP group (18.9 ± 2.3 h vs. 9.0 ± 0.8 h, p < 0.01).
CONCLUSIONS: ETR-P1/fl treatment significantly attenuated the elevation of NOx, TNF-α, and HMGB-1, which improved the systemic hypotension, pulmonary hypertension, and blood gases, thereby causing improvement of survival time in a progressive neonatal sepsis CLP model.
Tatenobu Goto; Mohamed Hamed Hussein; Shin Kato; Ghada Abdel-Hamid Daoud; Takenori Kato; Hiroki Kakita; Haruo Mizuno; Masaki Imai; Tetsuya Ito; Ineko Kato; Satoshi Suzuki; Noriko Okada; Hajime Togari; Hidechika Okada
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Publication Detail:
Type:  Journal Article     Date:  2010-09-16
Journal Detail:
Title:  Intensive care medicine     Volume:  36     ISSN:  1432-1238     ISO Abbreviation:  Intensive Care Med     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7704851     Medline TA:  Intensive Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2132-9     Citation Subset:  IM    
Department of Pediatrics and Neonatology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-Cho, Mizuho-Ku, Nagoya, 467-8601, Japan.
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