title: Edaravone, a hydroxyl radical scavenger, ameliorates the severity of pulmonary hypertension in a porcine model of neonatal sepsis.
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.
authors.affiliation: Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: Mohamed Hamed
authors.initials: MH
authors.lastname: Hussein
authors.forename: Ghada AbdEl-Hamid
authors.initials: GA
authors.lastname: Daoud
authors.forename: Tatenobu
authors.initials: T
authors.lastname: Goto
authors.forename: Shin
authors.initials: S
authors.lastname: Kato
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kakita
authors.forename: Haruo
authors.initials: H
authors.lastname: Mizuno
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ito
authors.forename: Sumio
authors.initials: S
authors.lastname: Fukuda
authors.forename: Ineko
authors.initials: I
authors.lastname: Kato
authors.forename: Satoshi
authors.initials: S
authors.lastname: Suzuki
authors.forename: Takashi
authors.initials: T
authors.lastname: Hashimoto
authors.forename: Hajime
authors.initials: H
authors.lastname: Togari
mesh_terms: D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D017665:Hydroxyl Radical / Q000378:metabolism*; D006976:Hypertension, Pulmonary / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D018805:Sepsis / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D016166:Free Radical Scavengers; D014409:Tumor Necrosis Factor-alpha; D017665:Hydroxyl Radical; D000077553:Edaravone; D000983:Antipyrine