Tohoku J. Exp. Med., 2011, 223(4)

Edaravone, a Hydroxyl Radical Scavenger, Ameliorates the Severity of Pulmonary Hypertension in a Porcine Model of Neonatal Sepsis

SACHIKO YAMAGUCHI,¹ MOHAMED HAMED HUSSEIN,^1,2,3,5 GHADA ABDEL-HAMID DAOUD,⁴ TATENOBU GOTO,¹ SHIN KATO,¹ HIROKI KAKITA,¹ HARUO MIZUNO,¹ TETSUYA ITO,¹ SUMIO FUKUDA,¹ INEKO KATO,¹ SATOSHI SUZUKI,¹ TAKASHI HASHIMOTO⁵ and HAJIME TOGARI¹

¹Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
²Neonatal Intensive Care Unit, Pediatric Hospital, Cairo University, Cairo, Egypt
³Research Center, VACSERA, Giza, Egypt
⁴Department of Obstetrics and Gynecology, VACSERA, Giza, Egypt
⁵Department of Pediatric Surgery, Fujita Health University School of Medicine, Toyoake, Japan

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.

keywords —— newborn; infection; septic shock; oxidative stress; circulation

© 2011 Tohoku University Medical Press

===============================

Tohoku J. Exp. Med., 2011, 223, 235-241

Correspondence: Mohamed Hamed Hussein, Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.

e-mail: hamed@med.nagoya-cu.ac.jp or drmhamed@yahoo.com