A Translational Study of a New Therapeutic Approach for Acute Myocardial Infarction:Nanoparticle-Mediated Delivery of Pitavastatin into Reperfused Myocardium Reduces Ischemia-Reperfusion Injury in a Preclinical Porcine Model

• Material Type: 博士論文
• Title: A Translational Study of a New Therapeutic Approach for Acute Myocardial Infarction:Nanoparticle-Mediated Delivery of Pitavastatin into Reperfused Myocardium Reduces Ischemia-Reperfusion Injury in a Preclinical Porcine Model
• Author/Editor: 市村, 研三
• Author Heading: 市村, 研三
• Publication Date: 2018-02-28
• Publication Date (W3CDTF): 2018-02-28
• Alternative Title: ピタバスタチン封入ナノ粒子による心筋虚血再灌流傷害に対する心保護的治療効果の検討-ブタモデルを用いた全臨床試験-
• Contributor: 笹栗, 俊之; 北園, 孝成; 塩瀬, 明
• Degree grantor/type: 九州大学
• Date Granted: 2018-02-28
• Date Granted (W3CDTF): 2018-02-28
• Dissertation Number: 甲第13900号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第13900号
• Text Language Code: eng
• Target Audience: 一般
• Note (General): Background: There is an unmet need to develop an innovative cardioprotective modality for acute myocardial infarction, for which interventional reperfusion therapy is hampered by ischemia-reperfusion (IR) injury. We recently reported that bioabsorbable poly(lactic acid/glycolic acid) (PLGA) nanoparticle-mediated treatment with pitavastatin (pitavastatin-NP) exerts a cardioprotective effect in a rat IR injury model by activating the PI3K-Akt pathway and inhibiting inflammation. To obtain preclinical proof-of-concept evidence, in this study, we examined the effect of pitavastatin-NP on myocardial IR injury in conscious and anesthetized pig models. / Methods and Results: Eighty-four Bama mini-pigs were surgically implanted with a pneumatic cuff occluder at the left circumflex coronary artery (LCx) and telemetry transmitters to continuously monitor electrocardiogram as well as to monitor arterial blood pressure and heart rate. The LCx was occluded for 60 minutes, followed by 24 hours of reperfusion under conscious conditions. Intravenous administration of pitavastatin-NP containing ≥ 8 mg/body of pitavastatin 5 minutes before reperfusion significantly reduced infarct size; by contrast, pitavastatin alone (8 mg/body) showed no therapeutic effects. Pitavastatin-NP produced anti-apoptotic effects on cultured cardiomyocytes in vitro. Cardiac magnetic resonance imaging performed 4 weeks after IR injury revealed that pitavastatin-NP reduced the extent of left ventricle remodeling. Importantly, pitavastatin-NP exerted no significant effects on blood pressure, heart rate, or serum biochemistry. Exploratory examinations in anesthetized pigs showed pharmacokinetic analysis and the effects of pitavastatin-NP on no-reflow phenomenon. / Conclusions: NP-mediated delivery of pitavastatin to IR-injured myocardium exerts cardioprotective effects on IR injury without apparent adverse side effects in a preclinical conscious pig model. Thus, pitavastatin-NP represents a novel therapeutic modality for IR injury in acute myocardial infarction.; PubMed番号 : 27603665
• DOI: 10.15017/1931753; https://doi.org/10.15017/1931753
• Persistent ID (NDL): info:ndljp/pid/11116161; https://dl.ndl.go.jp/pid/11116161
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2018-07-03T21:49:10+09:00
• Date Created (W3CDTF): 2018-05-30
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://dx.doi.org/10.15017/1931753; http://hdl.handle.net/2324/1931753
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp

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