Edaravone, a hydroxyl radical Scavenger, ameliorates the severity of pulmonary hypertension in a porcine model of neonatal sepsis

Sachiko Yamaguchi, Mohamed Hamed Hussein, Ghada Abd El Hamid Daoud, Tatenobu Goto, Shin Kato, Hiroki Kakita, Haruo Mizuno, Tetsuya Ito, Sumio Fukuda, Ineko Kato, Satoshi Suzuki, Lakashi Hashimoto, Hajime Togari

Research output: Contribution to journalArticle

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Abstract

Systemic infection in the newborn (neonatal sepsis) is the most common cause of neonatal mortality. Neonatal sepsis is complicated by pulmonary hypertension. In this study, we analyzed the effect of edaravone, a free radical scavenger that is known to reduce the production of inflammatory mediators, such as tumor necrosis factor α (TNFα), on pulmonary hypertension. Experimental and sham groups were drawn from 19 three-day-old piglets; 5 underwent a modified procedure of cecal ligation and perforation (CLP) (CLP group), 8 underwent CLP followed 30 min later by edaravone intravenous administration (edaravone group), and 6 did not undergo CLP and did not receive edaravone (sham group). To evaluate the pulmonary blood pressure despite the sepsis-induced low cardiac output, mean arterial blood pressure (mABP), mean pulmonary arterial pressure (mPAP), and comparative pulmonary hypertension ratio (mPAP/ mABP) were determined. Serum TNFα levels were measured before the procedure and at 1, 3, and 6 h after. The mPAP levels were higher in the CLP group at 9 h compared to the edaravone group. The mPAP/mABP ratio was lower in the edaravone and sham groups compared to the CLP group at 6 and 9 h. TNFα in the edaravone and sham groups were lower at 1 and 3 h compared to that in the CLP group. In all animals, mPAP/mABP at 6 h correlated with serum levels of TNFα at 1, 3, and 6 h. These findings suggest that edaravone ameliorates the severity of pulmonary hypertension in a neonatal sepsis model by reducing serum TNFα levels.

Original languageEnglish
Pages (from-to)235-241
Number of pages7
JournalTohoku Journal of Experimental Medicine
Volume223
Issue number4
DOIs
Publication statusPublished - 11-04-2011

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Pulmonary Hypertension
Hydroxyl Radical
Arterial Pressure
Swine
Blood pressure
Tumor Necrosis Factor-alpha
Ligation
Lung
Free Radical Scavengers
Neonatal Sepsis
phenylmethylpyrazolone
Serum
Animals
Low Cardiac Output
Infant Mortality
Intravenous Administration
Sepsis
Blood Pressure

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Yamaguchi, Sachiko ; Hussein, Mohamed Hamed ; Daoud, Ghada Abd El Hamid ; Goto, Tatenobu ; Kato, Shin ; Kakita, Hiroki ; Mizuno, Haruo ; Ito, Tetsuya ; Fukuda, Sumio ; Kato, Ineko ; Suzuki, Satoshi ; Hashimoto, Lakashi ; Togari, Hajime. / Edaravone, a hydroxyl radical Scavenger, ameliorates the severity of pulmonary hypertension in a porcine model of neonatal sepsis. In: Tohoku Journal of Experimental Medicine. 2011 ; Vol. 223, No. 4. pp. 235-241.
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abstract = "Systemic infection in the newborn (neonatal sepsis) is the most common cause of neonatal mortality. Neonatal sepsis is complicated by pulmonary hypertension. In this study, we analyzed the effect of edaravone, a free radical scavenger that is known to reduce the production of inflammatory mediators, such as tumor necrosis factor α (TNFα), on pulmonary hypertension. Experimental and sham groups were drawn from 19 three-day-old piglets; 5 underwent a modified procedure of cecal ligation and perforation (CLP) (CLP group), 8 underwent CLP followed 30 min later by edaravone intravenous administration (edaravone group), and 6 did not undergo CLP and did not receive edaravone (sham group). To evaluate the pulmonary blood pressure despite the sepsis-induced low cardiac output, mean arterial blood pressure (mABP), mean pulmonary arterial pressure (mPAP), and comparative pulmonary hypertension ratio (mPAP/ mABP) were determined. Serum TNFα levels were measured before the procedure and at 1, 3, and 6 h after. The mPAP levels were higher in the CLP group at 9 h compared to the edaravone group. The mPAP/mABP ratio was lower in the edaravone and sham groups compared to the CLP group at 6 and 9 h. TNFα in the edaravone and sham groups were lower at 1 and 3 h compared to that in the CLP group. In all animals, mPAP/mABP at 6 h correlated with serum levels of TNFα at 1, 3, and 6 h. These findings suggest that edaravone ameliorates the severity of pulmonary hypertension in a neonatal sepsis model by reducing serum TNFα levels.",
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Yamaguchi, S, Hussein, MH, Daoud, GAEH, Goto, T, Kato, S, Kakita, H, Mizuno, H, Ito, T, Fukuda, S, Kato, I, Suzuki, S, Hashimoto, L & Togari, H 2011, 'Edaravone, a hydroxyl radical Scavenger, ameliorates the severity of pulmonary hypertension in a porcine model of neonatal sepsis', Tohoku Journal of Experimental Medicine, vol. 223, no. 4, pp. 235-241. https://doi.org/10.1620/tjem.223.235

Edaravone, a hydroxyl radical Scavenger, ameliorates the severity of pulmonary hypertension in a porcine model of neonatal sepsis. / Yamaguchi, Sachiko; Hussein, Mohamed Hamed; Daoud, Ghada Abd El Hamid; Goto, Tatenobu; Kato, Shin; Kakita, Hiroki; Mizuno, Haruo; Ito, Tetsuya; Fukuda, Sumio; Kato, Ineko; Suzuki, Satoshi; Hashimoto, Lakashi; Togari, Hajime.

In: Tohoku Journal of Experimental Medicine, Vol. 223, No. 4, 11.04.2011, p. 235-241.

Research output: Contribution to journalArticle

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T1 - Edaravone, a hydroxyl radical Scavenger, ameliorates the severity of pulmonary hypertension in a porcine model of neonatal sepsis

AU - Yamaguchi, Sachiko

AU - Hussein, Mohamed Hamed

AU - Daoud, Ghada Abd El Hamid

AU - Goto, Tatenobu

AU - Kato, Shin

AU - Kakita, Hiroki

AU - Mizuno, Haruo

AU - Ito, Tetsuya

AU - Fukuda, Sumio

AU - Kato, Ineko

AU - Suzuki, Satoshi

AU - Hashimoto, Lakashi

AU - Togari, Hajime

PY - 2011/4/11

Y1 - 2011/4/11

N2 - Systemic infection in the newborn (neonatal sepsis) is the most common cause of neonatal mortality. Neonatal sepsis is complicated by pulmonary hypertension. In this study, we analyzed the effect of edaravone, a free radical scavenger that is known to reduce the production of inflammatory mediators, such as tumor necrosis factor α (TNFα), on pulmonary hypertension. Experimental and sham groups were drawn from 19 three-day-old piglets; 5 underwent a modified procedure of cecal ligation and perforation (CLP) (CLP group), 8 underwent CLP followed 30 min later by edaravone intravenous administration (edaravone group), and 6 did not undergo CLP and did not receive edaravone (sham group). To evaluate the pulmonary blood pressure despite the sepsis-induced low cardiac output, mean arterial blood pressure (mABP), mean pulmonary arterial pressure (mPAP), and comparative pulmonary hypertension ratio (mPAP/ mABP) were determined. Serum TNFα levels were measured before the procedure and at 1, 3, and 6 h after. The mPAP levels were higher in the CLP group at 9 h compared to the edaravone group. The mPAP/mABP ratio was lower in the edaravone and sham groups compared to the CLP group at 6 and 9 h. TNFα in the edaravone and sham groups were lower at 1 and 3 h compared to that in the CLP group. In all animals, mPAP/mABP at 6 h correlated with serum levels of TNFα at 1, 3, and 6 h. These findings suggest that edaravone ameliorates the severity of pulmonary hypertension in a neonatal sepsis model by reducing serum TNFα levels.

AB - Systemic infection in the newborn (neonatal sepsis) is the most common cause of neonatal mortality. Neonatal sepsis is complicated by pulmonary hypertension. In this study, we analyzed the effect of edaravone, a free radical scavenger that is known to reduce the production of inflammatory mediators, such as tumor necrosis factor α (TNFα), on pulmonary hypertension. Experimental and sham groups were drawn from 19 three-day-old piglets; 5 underwent a modified procedure of cecal ligation and perforation (CLP) (CLP group), 8 underwent CLP followed 30 min later by edaravone intravenous administration (edaravone group), and 6 did not undergo CLP and did not receive edaravone (sham group). To evaluate the pulmonary blood pressure despite the sepsis-induced low cardiac output, mean arterial blood pressure (mABP), mean pulmonary arterial pressure (mPAP), and comparative pulmonary hypertension ratio (mPAP/ mABP) were determined. Serum TNFα levels were measured before the procedure and at 1, 3, and 6 h after. The mPAP levels were higher in the CLP group at 9 h compared to the edaravone group. The mPAP/mABP ratio was lower in the edaravone and sham groups compared to the CLP group at 6 and 9 h. TNFα in the edaravone and sham groups were lower at 1 and 3 h compared to that in the CLP group. In all animals, mPAP/mABP at 6 h correlated with serum levels of TNFα at 1, 3, and 6 h. These findings suggest that edaravone ameliorates the severity of pulmonary hypertension in a neonatal sepsis model by reducing serum TNFα levels.

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