2011-05-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/649159摘要：在美國2009年估計心衰竭的直接和間接醫療費用達三百七十二億美元。葉克膜（Extracorporeal membrane oxygenation, ECMO）提供嚴重心臟衰竭患者短期的機械循環支持和給予的機會恢復或心臟移植。 B-Natriuretic paptide(BNP): 心肌細胞合成proBNP（1-108），並分解成 BNP（1-32）和NT - proBNP。只有BNP（1-32）的生理活性，同時 NT - proBNP和Pro-BNP不具任何生理作用。BNP提高尿量和血管擴張，這有利於患者容量超負荷狀態，如心臟衰竭。 血中BNP的濃度被認為是一個心臟衰竭的標誌。目前有三種主要的商業的BNP檢測試劑。然而，所有檢測試劑和不具任何生理作用的Pro-BNP有交叉反應。 BNP的測量應用在葉克膜患者是我們醫院的獨特應用，我們已經發表初步結果。深入研究BNP系統，包括它的各種形式和轉換酶可能有很大的潛力進一步改善其臨床指標的準確及應用在加護病房及葉克膜患者的監測。本研究的目的是探討在葉克膜患者B -利鈉肽（BNP）的系統，包括proBNP，BNP，N -端proBNP(NT - proBNP），轉換酶（Corin）濃度，並找到作為一種生物標誌物的臨床意義，指導治療。 方法： 將收集葉克膜患者的血液。我們計劃收集50個病人中。利用免疫沉澱與 BNP和NT - proBNP的特異抗體和SDS - PAGE電泳，分別定量測量BNP（4 kDa），NT - proBNP（8 kDa）和proBNP（12 kDa）的量。Biosite BNP和羅氏NT - proBNP的檢測將被用於比較。 Corin的血漿濃度將用ELISA檢測。BNP(1-32)可再被DPP IV切成BNP(3-32). BNP(4-32)也被報告在心衰竭病患報告其生理意義未明 因此計劃更進一步將利用質譜(Mass spectrometry MS)免疫沉澱和SDS - PAGE研究各種形式的BNP（1-32，3-32，4-32）。研究是否在葉克膜患者產生的BNP 具有不同形式。 這些數據將是相關病人的生理參數和臨床過程，以使一個生物標記，以做為葉克膜患者或心衰竭的新治療標計或新藥開發的基礎。<br> Abstract: Heart failure is a common cardiac condition and the estimated direct and indirect cost of heart failureF in the United States for 2009 is $37.2 billion. Extracorporeal membrane oxygenation support (ECMO) provides short-term mechanical circulation support and give chance of recovery or bridge to heart transplantation in patients with severe heart failure status.The cardiomyocyte synthesizes proBNP (1-108), and enzymatically cuts it into BNP(1-32) and NT-proBNP. Only BNP (1-32) is physiologically active; both NT-proBNP and pro-BNP do not exert any physiologic effect. BNP enhances urine output and vasodilatation, which is beneficial for patients in volume overload status, such as heart failure.The level of BNP was considered as a marker of heart failure. There are currently three major commercial kits for BNP system detection. However, all have cross-reactive with the circulation, non-functioning Pro-BNP.The application of BNP measurement in patients with ECMO support is unique in our hospital, and we have publication in this topic. Further understanding of the BNP system including its various form and converting enzymes may have great potential to further improvement of the clinical managements in the critical setting. The purpose of this study is to investigate the B-natriuretic peptide (BNP) system, including the proBNP, BNP, N-terminal proBNP (NT-proBNP), converting enzyme (Corin), and various form of circulation BNP(1-32,3-32,4-32) in patients with extracorporeal membrane oxygenation support (ECMO), and find the clinical implication as a biomarker to guide therapy.Methods:Blood samples will be collected from HF patients needing ECMO support. We plan to collect 50 patients in this study. For specific measurement of BNP, NT-proBNP, and proBNP, plasma immunoglobulins and albumin will be first depleted with commercial depletion column, immuno-precipitated with commercial BNP and NT-proBNP antibodies and protein A beads, resolved with SDS-PAGE, electro-transferred-to membrane, and finally detected with BNP and NT-proBNP antibodies. BNP (4 kDa), NT-proBNP (8 kDa) and proBNP (12 kDa) will be identified by sizes as well as synthetic controls and the relative ratio will be assessed and correlated with patient’s outcome. Commercial available kits, the Biosite Triage BNP test for measuring BNP and proBNP, and the Roche NT-ProBNP test for detecting proBNP and NT-proBNP will be used for comparison.The plasma corin levels will be measured with commercial ELISA kits. The various forms of circulation BNP(1-32, 3-32,4-32) have need reported, but the clinical implication is not clear yet. So, the relation between various forms of BNP (1-32, 3-32, 4-32) and the outcome of patients will be the next approach. The same immuno-precipitation and SDS-PAGE process will be conducted; BNP spots will be cut, gel-eluted, and finally analyzed by Mass spectrometry (MS) to understand the exact BNP forms in the patients.The data will be correlated to the patients' physiologic parameter and the clinical course, in order to make a biomarker to guide daily therapy for heart failure patients with ECMO support; and served as further development of new drug/intervention.心臟衰竭葉克膜B -利鈉肽