2014-08-012024-05-14https://scholars.lib.ntu.edu.tw/handle/123456789/656051摘要：背景：大約有 10%的瓣膜開心手術在手術台上有可能需要再次阻斷心臟血流以進行後續手術，特別是複雜的二尖瓣膜或主動瓣膜整形手術。心臟的『前置保護』和『後置保護』早於 1986 年及 1993 年就分別被提出，並且其機轉已在實驗室被深入研究。從『前置保護』和『後置保護』的觀點來分析，心臟剛從第一次缺血恢復時，心肌正承受『缺血』的傷害並正逐漸展開『再灌流』的傷害，所以，『何時』和『如何』去執行心臟第二次缺血可能對其後心臟的『缺血/再灌流』傷害以及心臟功能的恢復有重大影響。 目標：本研究計劃擬研究下列主題(1)兩次缺血間最佳的『再灌流』時間(我們好奇究竟是『越短越好』還是『越長越好』)(2)以『缺血/再灌流』的觀點，不同種類的心臟保護液是否有不同的效果(我們的假說是 HTK 可讓細胞內代謝停止，以減少毒素累積並減低再灌流傷害)(3)是否在第一次缺血前後加入『前置保護』或『後置保護』的措施，能減低其後的缺血/再灌流傷害並改善心臟功能。 方法：本研究計劃以成年猪為對象，施與體外循環，經過兩次各 60 分鐘的主動脈橫夾，在第二次橫夾放開之後，經過 60 分鐘再灌流後，停止體外循環，接受左心室壓力-體積曲線圖檢查以測量左心室功能。其後摘取心臟以進行心肌壞死及心肌凋亡的測量。在兩次心臟缺血之後分別執行心肌切片以測量心臟缺血/重灌流的傷害程度的生化指標。 『計劃一』乃研究兩次缺血之間的時間長短，是否會影響最終心臟的功能及心肌傷害。我們選擇 10 分鐘，20 分鐘，40 分鐘作為三組之變項。 『計劃二』乃研究不同形式的心臟保護液是否會影響最終的心臟功能及心肌傷害。我們選擇兩種心肌保護液，Plegisol 和 HTK，分別於兩次心肌缺血前灌注不同的心臟保護液(共四組)。 『計劃三』乃研究在第一次缺血時增加『前置保護』或『後置保護』的措施，是否可改善最後心臟功能。『前置保護』可以於主動脈橫夾前施與三次短暫(30 秒)的暫時性心臟缺血完成，而『後置保護』可以於放開主動脈橫夾前施與三次短暫(30 秒)的暫時性心臟灌流完成。我們將比較『對照組』，『前置保護組』，『後置保護組』，以及『前置保護加後置保護組』共四組。 預期成果：本研究預期可強化吾人對『前置保護』及『後置保護』的認識及轉譯至臨床應用。它可幫助心臟外科醫師找到最佳的心臟保護策略萬一在手術台上需要施與再次心臟缺血。這些研究成果將可幫助心臟外科醫師完美的並安全的執行困難的及複雜的開心手術。<br> Abstract: Background: About 10% of heart valve surgery may encounter repeated cardiac arrest and further operative procedure during the operation, mostly due to complex mitral valve or aortic valve plasty operation. Myocardial pre-conditioning and post-conditioning were proposed early in 1986 and 1993, respectively, and are well studied in laboratory. Theoretically, the heart just after first ischemic episode suffers from ischemic injury and is beginning to have reperfusion damage. Therefore, “when” and “how” to apply the second aortic cross-clamping may be critical for later myocardial damage and functional recovery. Aim: To evaluate (1) the optimal interval between two ischemic episodes (we wonder that the longer the better or the shorter the better) (2) Impact of types of cardioplegia on ischemia/reperfusion injury (we hypothesize the HTK decreases intracellular metabolism and reduces toxin accumulation and later reperfusion injury) (3) Whether adding pre-conditioning or post-conditioning strategies during first arrest period can decrease reperfusion injury and preserve myocardial function. Methods: the present study uses adult swine under anesthesia and cardiopulmonary bypass. Two episodes of 60-minute aortic clamping are applied. After the second ischemic episode, 60-minute reperfusion is allowed before cardiopulmonary bypass is off and left ventricular systolic and diastolic function study is performed with pressure-volume loop analysis. Then the heart is prepared for necrosis and apoptosis study. Myocardial biopsies for the markers of ischemia/reperfusion damage are taken after the first and second ischemic periods, respectively. The primary aim in “study 1” is to determine whether short or long duration between two ischemic periods has influence on final LV injury. We choose 10 minutes, 20 minutes, and 40 minutes in different study groups, respectively. The primary aim in “study 2” is to determine whether different combinations of cardioplegia have influence on final LV injury. We use two types of cardioplegia in the study, Plegisol and HTK. We design a two-by-two combination of two cardioplegias in four study groups, respectively. The primary aim in “study 3” is to determine whether adding pre-conditioning or post-conditioning strategy has influence on final LV injury. Mechanical pre-conditioning can be achieved with three times of transient myocardial perfusion before apply of aortic clamp, and mechanical post-conditioning can be achieved with three times of transient myocardial perfusion (30 seconds) before relief of aortic clamp. We compare four groups in this study: control, pre-conditioning, post-conditioning, pre- and post-conditioning. Potential contribution: The present study can consolidate the knowledge about pre-conditioning and post-conditioning and translate to clinical medicine. As well, it can help us to find out the best policy for myocardial protection in case repeated cardiac arrest is needed. All these knowledge can help cardiac surgeons to successfully deal with difficult open heart surgery and make open heart surgery more perfect and safe.前置保護後置保護開心手術瓣膜手術 表pre-conditioningpost-conditioningopen heart surgeryvalve surgery