Therapeutic time-window of a group IIA phospholipase A2 inhibitor in rabbit acute lung injury: Correlation with lung surfactant protection

作者：Shingo Furue, Katsuya Mikawa, Kahoru Nishina, Makoto Shiga, Masahiko Ueno, Yasuhiko Tomita, Kenji Kuwabara, Isao Teshirogi, Takashi Ono, Yozo Hori, Akihiro Matsukawa, Masaru Yoshinaga, Hidefumi Obara · 发表于：Critical Care Medicine · 年份：2001 · DOI：10.1097/00003246-200104000-00004 · 被引用次数：62 · 研究领域：Neonatal Respiratory Health Research、Respiratory Support and Mechanisms、Trauma, Hemostasis, Coagulopathy, Resuscitation

OBJECTIVE: We attempted to determine whether group IIA secretory phospholipase A2 (sPLA2-IIA) blockade after the onset of lung injury exerted therapeutic efficacy in the treatment of oleic acid (OA)-induced acute lung injury by using S-5920/LY315920Na, a novel specific inhibitor of sPLA2-IIA, with special interest in the changes of lung surfactant. DESIGN: Prospective animal study. SETTING: University laboratory. SUBJECTS: Forty Japanese white rabbits. INTERVENTIONS: The rabbits, under anesthesia, were endotracheally intubated and mechanically ventilated and then were divided into the following groups: OA + vehicle groups, intravenous infusion of OA for the first 2 hrs (0.1 mL x kg(-1) x hr(-1)) with the addition of vehicle (1 or 2 hrs after OA administration, each n = 9, total 18 rabbits); OA + S-5920/LY315920Na groups, treated identically to the OA control with the addition of S-5920/LY315920Na (1 mg/kg bolus followed by infusion at 0.5 mg x kg(-1) x hr(-1)) after OA (1 or 2 hrs after OA administration, each n = 9, total 18 rabbits); saline control groups, treated with saline instead of OA with the addition of vehicle (1 hr after OA administration, 4 rabbits). Arterial blood gas, lung mechanics, lung inflammation, lung surfactant phospholipids, and production of inflammatory mediators in the lung were measured. MEASUREMENTS AND MAIN RESULTS: Treatment with S-5920/LY315920Na 1 hr after OA infusion, but not 2 hrs after infusion, significantly attenuated the lung injury, as es...