【摘要】：背景:復(fù)蘇技術(shù)的進(jìn)步已使自主循環(huán)的恢復(fù)率顯著提升,然而心臟驟停的發(fā)生率和死亡率依然很高。復(fù)蘇后心功能障礙是心臟驟停復(fù)蘇后72h內(nèi)高死亡率的主要原因。雖然復(fù)蘇后心功能障礙被認(rèn)為是暫時(shí)性的,但它與心臟驟停后動(dòng)脈血壓降低和低心輸出量相關(guān),旨在改善復(fù)蘇后心功能障礙的干預(yù)措施可使臨床受益。尼可地爾作為一種ATP敏感鉀通道開(kāi)放劑,是臨床上用于治療冠狀動(dòng)脈疾病的標(biāo)準(zhǔn)用藥。基礎(chǔ)和臨床研究證據(jù)均顯示尼可地爾可改善心臟缺血后收縮功能障礙,使冠狀動(dòng)脈閉塞和再灌注后心肌梗死面積縮小,然而關(guān)于尼可地爾在心臟驟停復(fù)蘇模型中的應(yīng)用研究仍然很少。目的:本研究用4min室顫誘發(fā)豬心臟驟停模型,探討尼可地爾對(duì)復(fù)蘇后心肌損傷的保護(hù)作用。方法:20頭長(zhǎng)白豬隨機(jī)分為假手術(shù)組(n=4)和復(fù)蘇組(n=16)。復(fù)蘇組在手術(shù)后給予電刺激誘導(dǎo)室顫,4min后行心肺復(fù)蘇術(shù)。假手術(shù)組給予手術(shù)而不誘發(fā)室顫。復(fù)蘇組16頭長(zhǎng)白豬復(fù)蘇成功并隨機(jī)分為鹽水對(duì)照組(n=8)和尼可地爾組(n=8),尼可地爾組即刻經(jīng)中央靜脈注射尼可地爾(150μg/kg),隨后以3μg/(kg·min)靜滴至再灌注結(jié)束;鹽水對(duì)照組給予同劑量生理鹽水。實(shí)驗(yàn)過(guò)程中連續(xù)監(jiān)測(cè)血流動(dòng)力學(xué)參數(shù):心率、平均動(dòng)脈壓、心輸出量、dp/dtmax和-dp/dtmax。致顫前和自主循環(huán)恢復(fù)后5、30、180和360min采取血樣以檢測(cè)肌鈣蛋白Ⅰ和乳酸水平。在致顫前和自主循環(huán)恢復(fù)后6h行心臟多普勒超聲評(píng)估左室射血分?jǐn)?shù)。在自主循環(huán)恢復(fù)后6h將動(dòng)物實(shí)施安樂(lè)死并留取心肌組織,行普通病理學(xué)及透射電鏡檢查觀察心肌組織學(xué)損傷,用TUNEL法檢測(cè)凋亡心肌細(xì)胞。用ELISA方法檢測(cè)心肌組織中ATP濃度,Western Blot方法檢測(cè)心肌組織中Bax、caspase-3和Bcl-2的表達(dá)。結(jié)果:自主循環(huán)恢復(fù)后6h,與鹽水對(duì)照組相比,除-dp/dtmax和心率外(P0.05),尼可地爾可顯著改善血流動(dòng)力學(xué)參數(shù),差異有統(tǒng)計(jì)學(xué)意義(P0.05)。與假手術(shù)組相比,鹽水對(duì)照組動(dòng)物的肌鈣蛋白Ⅰ和乳酸水平復(fù)蘇成功后升高,尼可地爾組使其水平顯著降低,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。與假手術(shù)組相比,鹽水對(duì)照組動(dòng)物的ATP濃度顯著降低,而尼可地爾組其降低程度顯著緩解,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。與鹽水對(duì)照組相比,尼可地爾組復(fù)蘇后心肌組織學(xué)損傷減輕,TUNEL陽(yáng)性細(xì)胞數(shù)目減少,差異有統(tǒng)計(jì)學(xué)意義(P0.05),心肌Bax和caspase-3的表達(dá)減少,Bcl-2的表達(dá)增加,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。結(jié)論:尼可地爾可改善復(fù)蘇后心功能障礙和能量代謝、減輕心肌組織學(xué)損傷和抗凋亡,從而對(duì)心臟驟停后心肌損傷產(chǎn)生保護(hù)作用。
[Abstract]:Background: advances in resuscitation have significantly increased the recovery rate of autonomic circulation, but the incidence and mortality of cardiac arrest remain high. Cardiac dysfunction after resuscitation was the main cause of high mortality within 72 hours after cardiac arrest. Although cardiac dysfunction after resuscitation is considered to be temporary, it is associated with decreased arterial blood pressure and low cardiac output after cardiac arrest. Intervention aimed at improving cardiac dysfunction after resuscitation may benefit clinical practice. As a ATP sensitive potassium channel opener, nicorandil is a standard drug for the treatment of coronary artery disease. Both basic and clinical studies have shown that nicorandil can improve the systolic dysfunction of the heart after ischemia and reduce myocardial infarction size after coronary artery occlusion and reperfusion. However, there are few studies on the application of nicordil in cardiac arrest and resuscitation models. Aim: to investigate the protective effect of nicorandil on myocardial injury after resuscitation in porcine cardiac arrest model induced by 4min ventricular fibrillation. Methods: 20 Landrace pigs were randomly divided into two groups: sham operation group (n = 4) and resuscitation group (n = 16). In the resuscitation group, electrical stimulation was given to induce ventricular fibrillation and cardiopulmonary resuscitation was performed after 4min. The sham group was given surgery without inducing ventricular fibrillation. Sixteen Landrace pigs in the resuscitation group were successfully resuscitated and randomly divided into two groups: saline control group (n = 8) and nicorandil group (n = 8). Nicodil (150 渭 g/kg) was immediately injected via central vein in nicorandil group. Then 3 渭 g / (kg min) was given intravenously to the end of reperfusion. Saline control group was given the same dose of normal saline. Continuous monitoring of hemodynamic parameters during the experiment: heart rate, mean arterial pressure, cardiac output, dp/dtmax and-dp/dtmax. Blood samples were taken to detect troponin I and lactate levels before fibrillation and after recovery of autonomic circulation. Left ventricular ejection fraction (LVEF) was evaluated by echocardiography before fibrillation and 6 hours after spontaneous circulation recovery. Euthanasia was performed 6 hours after the recovery of autonomic circulation and myocardial tissue was taken. The histological damage of myocardium was observed by general pathology and transmission electron microscopy. Apoptotic cardiomyocytes were detected by TUNEL method. The expression of Bax,caspase-3 and Bcl-2 in myocardial tissue was detected by ELISA and, Western Blot. Results: compared with saline control group, nicorandil significantly improved hemodynamic parameters except-dp/dtmax and heart rate (P0.05) at 6 h after recovery of autonomic circulation (P0.05). Compared with the sham operation group, the level of troponin I and lactate in saline control group increased after successful resuscitation, but the level of nicorandil group decreased significantly (P0.05). Compared with the sham operation group, the concentration of ATP in the saline control group was significantly lower than that in the nicorandil group (P0.05). Compared with the saline control group, the myocardial tissue injury and the number of TUNEL positive cells decreased after resuscitation in the nicorandil group (P0.05). The expression of Bax and caspase-3 decreased and the expression of Bcl-2 increased in the myocardium of nicorandil group. The difference was statistically significant (P0.05). Conclusion: nicorandil can improve cardiac dysfunction and energy metabolism after resuscitation, alleviate myocardial tissue injury and anti-apoptosis, and thus protect myocardium from cardiac arrest.
【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R541.78

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