2012-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/649320摘要：背景：低溫療法是目前在急救科學很重要的議題。 我們先前的研究發現體外心肺復甦術 (ECMO assisted cardiopulmonary resuscitation, ECPR) 和傳統的急救方式比較起來預後較好。而使用葉克膜的病人若要調控體溫並不困難，只要調整體外加溫器的溫度即可達到目標溫度。 然而目前並沒有關於低溫療法應用於 ECPR 的病人的分組對照研究。去年，我們建立了 ECPR 的低溫動物實驗模組，低溫療法導致了血管收縮和凝血病變，相關的人類和動物急救研究都顯示在急救後的病程有明顯的微循環(microcirculation) 改變，這在嚴重敗血症時也觀察到的，微循環功能異常可在足夠的組織供氧量下仍然造成細胞缺氧，目前關於改善微循環已成為治療急救後病程(postresuscitation phase) 的主要目標。所以我們擬定此為期兩年的動物實驗計畫，觀察 ECPR 後有無低溫治療是否對微循環有影響。第一年我們將比較ECPR 急救後低體溫和正常體溫的微循環，希望可以解答是否低體溫可以改善微循環。第二年我們將嘗試以硝化甘油 (nitroglycerin) 用在ECPR 急救後的動物，來改善微循環。在臨床觀察中，靜脈注射硝化甘油可在心因性休克的病人改善微循環，我們好奇是否在 ECPR 後，硝化甘油在此種急救後的低灌流症候群是否能改善微循環。方法：本實驗採用的動物模組是 20-25 公斤的豬。 以電擊方式造成心室顫動心臟停止。ECMO-CPR 開始運作後把動物分成兩組：對照組是體溫正常組 (n=5) ，體溫控制在 38 ℃ 維持六小時。實驗組是低溫組(n=5)，體溫控制在32 ℃ 維持四小時，然後在兩小時內回溫到 38 ℃。如此使用六小時的 ECMO 後，把 ECMO 關掉並移除管路， 等待動物恢復並記錄結果。實驗室檢查：我們每三十分鐘抽動脈血液做血液動脈氣體分析和乳酸值， 而血球計數 (CBC)、肝腎功能 (GOT GPT BUN CRE)、心肌酵素 (CK CKMB troponin I) ，則是在實驗開始時抽一基本值，心跳停止後六小時 和隔日會再抽血做檢驗。微循環檢查：我們會在實驗動物腹部開一小傷口，取出一小段末端結腸，做顯微鏡檢觀察。我們用 OPS (Microscan ) 來觀察並記錄微循環，接著我們用軟體分析微血流 收集這些微循環資料的時間點，將在心跳停止前，啟用葉克膜 30 分鐘後，移除葉克膜前及移除後三十分鐘，我們將比較低體溫和正常體溫的兩組動物。第二年，這兩組動物都將接受靜脈注射硝化甘油，再比較微循環的改變，看注射硝化甘油是否可改善微循環，及低溫組和常溫組的效果。<br> Abstract: Background:Hypothermic therapy is an important issue in resuscitation medicine. In our previous studies, ECMO assisted cardiopulmonary resuscitation (ECPR) was associated with improved outcome in patients with prolonged resuscitation. Hypothermia could be easily induced by adjust the temperature control system in ECMO. However, there is no study on hypothermia in ECPR patients.In last year, we have set-up the animal model for ECMO resuscitation. The hypothermia therapy resulted in vasoconstriction and coagulopathy. The human and animal studies of resuscitation showed that alternation of microcirculation is evident in post-resuscitation phase, or post-resuscitation syndrome, which is frequent observed in severe sepsis.Microcirculation dysfunction can contribute to cellular hypoxia even when global oxygen delivery is preserved. Since the improvement of microcirculation is one of the major target in post-resuscitation phase, we want to make a two-year study on microcirculation in animal model of ECMO-CPR with or without hypothermia.The first year will compare the microcirculation between hypothermia and normothermia, we want to answer the question that if hypothermia could improve microcirculation or not in ECMO-assisted CPR.The second year will study on nitroglycerin to improve microcirculation in ECMO assisted CPR. In clinical observation, nitroglycerin infusion had shown to improve microcirculation in patients with cardiogenic shock. We want to evaluate if the nitroglycerin could improve microcirculation in the setting of ECMO-CPR.Material and method.Pigs of either sex, 20 to 25 kg are applied in the study. They will be anesthetized with monitor equipment included with pulse oximetry, ECG, arterial pressure, central venous pressure and blood gas analysis throughout the whole procedure. The arrest model is performed by induced ventricular fibrillation, after a 15 minutes of no flow phase, ECMO will be performed with bypass flow was set at 100ml/kg/min.In the normothermia group(n=5), the temperature was controlled at 38°C, and maintained for 6 hours.In the hypothermia group(n=5), the temperature was cooled to 32°C, and maintained for 4 hours, and then rewarm to 38 °C in 2 hours.After 6 hours of ECMO support, the ECMO are turned off and decannulated, the animals was recovered and the outcome are recorded.Laboratory studyThe arterial blood gas will be sampled in every 30 minutes. The acid-base will be corrected to normal as clinical practice. Blood lactate level, will be checked every 30 minutes.The baseline CBC, GOT/GPT, BUN/Cre, CK/CKMB, cardiac troponin I, was sampled, and the second sample are collected at 6 hours after arrest, and then the next day after arrest.Microcirculation study:The A small segment of the terminal ileum was exteriorized via a small laparotomy for microscopic observation. The microcirculation will be monitored by OPS (MicroscanL) and recorded. In a second step, a semiquantitative analysis of the microflow is possible by software analysis. The microcirculation data will be collected before arrest, 30 minutes after ECMO initiation, before wean-off ECMO, and 30 minutes after weaning off ECMO, and compared between the hypothermia and normothermia groups. .We will compare the microcirculation data between the two groups, and correlated with the blood gas, lactate, biochemistry and hemodynamic data..In the second year, will add nitroglycerin infusion in each group, and compare with the treated and control group to see if microcirculation could be improved by nitroglycerin.低溫體外循環輔助心肺復甦術微循環