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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)2132-2139
Number of pages8
JournalIntensive Care Medicine
Volume36
Issue number12
DOIs
Publication statusPublished - 01-12-2010

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Arterial Pressure
Tumor Necrosis Factor-alpha
Pulmonary Hypertension
Cardiac Output
Ligation
Gases
HMGB1 Protein
Nitrites
Nitrates
Hypotension
Shock
Heart Rate
Neonatal Sepsis
Endothelin Receptor Antagonists
Oxygen
Lung
Peptides
Serum

All Science Journal Classification (ASJC) codes

  • Critical Care and Intensive Care Medicine

Cite this

Goto, Tatenobu ; Hussein, Mohamed Hamed ; Kato, Shin ; Daoud, Ghada Abdel Hamid ; Kato, Takenori ; Kakita, Hiroki ; Mizuno, Haruo ; Imai, Masaki ; Ito, Tetsuya ; Kato, Ineko ; Suzuki, Satoshi ; Okada, Noriko ; Togari, Hajime ; Okada, Hidechika. / Endothelin receptor antagonist attenuates inflammatory response and prolongs the survival time in a neonatal sepsis model. In: Intensive Care Medicine. 2010 ; Vol. 36, No. 12. pp. 2132-2139.
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abstract = "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.",
author = "Tatenobu Goto and Hussein, {Mohamed Hamed} and Shin Kato and Daoud, {Ghada Abdel Hamid} and Takenori Kato and Hiroki Kakita and Haruo Mizuno and Masaki Imai and Tetsuya Ito and Ineko Kato and Satoshi Suzuki and Noriko Okada and Hajime Togari and Hidechika Okada",
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Goto, T, Hussein, MH, Kato, S, Daoud, GAH, 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, vol. 36, no. 12, pp. 2132-2139. https://doi.org/10.1007/s00134-010-2040-0

Endothelin receptor antagonist attenuates inflammatory response and prolongs the survival time in a neonatal sepsis model. / Goto, Tatenobu; Hussein, Mohamed Hamed; Kato, Shin; Daoud, Ghada Abdel Hamid; Kato, Takenori; Kakita, Hiroki; Mizuno, Haruo; Imai, Masaki; Ito, Tetsuya; Kato, Ineko; Suzuki, Satoshi; Okada, Noriko; Togari, Hajime; Okada, Hidechika.

In: Intensive Care Medicine, Vol. 36, No. 12, 01.12.2010, p. 2132-2139.

Research output: Contribution to journalArticle

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T1 - Endothelin receptor antagonist attenuates inflammatory response and prolongs the survival time in a neonatal sepsis model

AU - Goto, Tatenobu

AU - Hussein, Mohamed Hamed

AU - Kato, Shin

AU - Daoud, Ghada Abdel Hamid

AU - Kato, Takenori

AU - Kakita, Hiroki

AU - Mizuno, Haruo

AU - Imai, Masaki

AU - Ito, Tetsuya

AU - Kato, Ineko

AU - Suzuki, Satoshi

AU - Okada, Noriko

AU - Togari, Hajime

AU - Okada, Hidechika

PY - 2010/12/1

Y1 - 2010/12/1

N2 - 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.

AB - 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.

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