Endothelin receptor antagonist attenuates inflammatory response and prolongs the survival time in a neonatal sepsis 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

研究成果: Article

9 引用 (Scopus)

抜粋

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.

元の言語English
ページ(範囲)2132-2139
ページ数8
ジャーナルIntensive Care Medicine
36
発行部数12
DOI
出版物ステータスPublished - 01-12-2010
外部発表Yes

All Science Journal Classification (ASJC) codes

  • Critical Care and Intensive Care Medicine

フィンガープリント Endothelin receptor antagonist attenuates inflammatory response and prolongs the survival time in a neonatal sepsis model' の研究トピックを掘り下げます。これらはともに一意のフィンガープリントを構成します。

  • これを引用

    Goto, T., Hussein, M. H., Kato, S., Daoud, G. A. H., Kato, T., Kakita, H., Mizuno, H., Imai, M., Ito, T., Kato, I., Suzuki, S., Okada, N., Togari, H., & Okada, H. (2010). Endothelin receptor antagonist attenuates inflammatory response and prolongs the survival time in a neonatal sepsis model. Intensive Care Medicine, 36(12), 2132-2139. https://doi.org/10.1007/s00134-010-2040-0