本文關(guān)鍵詞： 哇巴因 心律失常 美托洛爾 自主神經(jīng)系統(tǒng) 量效關(guān)系　出處：《山西醫(yī)科大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：目的:1.觀察美托洛爾對(duì)哇巴因致大鼠心律失常作用的影響,并探討β受體阻斷劑(β-blocker)應(yīng)用于洋地黃類藥物中毒的相關(guān)機(jī)制;2.應(yīng)用langendorff離體心臟灌流系統(tǒng),對(duì)哇巴因抑制離體大鼠心臟功能的時(shí)反應(yīng)量-效關(guān)系(Timed dose-response relationship,TDRR)進(jìn)行了觀察和分析。方法:1.應(yīng)用Langendorff灌流裝置進(jìn)行離體心臟灌流試驗(yàn),正常SD大鼠隨機(jī)分成5組:正常對(duì)照組,哇巴因模型組和4、20及100μmol/L美托洛爾干預(yù)組,每組8只動(dòng)物;記錄給入哇巴因后固定時(shí)間內(nèi)各組自主發(fā)生的室性期前收縮PVB數(shù)目,室速及室顫的發(fā)生率,記錄時(shí)間為60分鐘。2.在體麻醉實(shí)驗(yàn)使用股靜脈注射給藥,正常SD大鼠隨機(jī)分為5組:正常對(duì)照組,哇巴因模型組,和0.4mg/kg、2mg/kg、10mg/kg美托洛爾干預(yù)組,每組8只動(dòng)物;觀察出現(xiàn)各種心律失常(VP、VT、BBB、VF)及心臟停搏(CA)出現(xiàn)的時(shí)間,并計(jì)算出現(xiàn)上述現(xiàn)象時(shí)哇巴因的累計(jì)用量。3.利用Langendorff灌流裝置進(jìn)行離體心臟灌流試驗(yàn),用臺(tái)式灌流液將哇巴因配置為3μmol/L、10μmol/L、30μmol/L、100mol/L、300mol/L、1000mol/L的6個(gè)濃度組,記錄各濃度組左側(cè)心室發(fā)展壓(LVDP)和左側(cè)心室舒張末壓力(LVEDP)的變化曲線,記錄時(shí)間為30分鐘。結(jié)果:1.離體心臟灌流實(shí)驗(yàn)中,統(tǒng)計(jì)60min內(nèi)各組的室性期前收縮(PVB)數(shù)目,室速(VT)、室顫(VF)發(fā)生率,未發(fā)現(xiàn)美托洛爾干預(yù)組與哇巴因模型組在心律失常各指標(biāo)之間存在顯著差異(P0.05);2.在體麻醉動(dòng)物實(shí)驗(yàn)中,應(yīng)用美托洛爾后可延長(zhǎng)哇巴因致室性心律失常(二聯(lián)律、短陣及持續(xù)性室性心動(dòng)過(guò)速)出現(xiàn)的時(shí)間,但哇巴因致傳導(dǎo)阻滯(束支阻滯及房室阻滯)的時(shí)間提前,室顫發(fā)生率顯著減少,動(dòng)物存活時(shí)間延長(zhǎng)。3.在對(duì)收縮功能的分析中發(fā)現(xiàn)哇巴因隨著濃度的升高(3~1000μmol/L),左心室發(fā)展壓(LVDP)抑制率增大,潛伏期縮短,達(dá)峰時(shí)間在低濃度(30μmol/L)延長(zhǎng)而高濃度(100μmol/L)縮短,平均抑制速率加快;在對(duì)舒張功能的分析中發(fā)現(xiàn)哇巴因隨著濃度的升高(3~1000μmol/L),左室舒張末壓(LVEDP)最大升高幅度增大,且隨著濃度升高出現(xiàn)潛伏期縮短,達(dá)到峰值時(shí)間延長(zhǎng),平均升高速率加快等效應(yīng)。結(jié)論:1.哇巴因在離體灌流心臟及在體條件下都可以穩(wěn)定的誘發(fā)出心律失常,美托洛爾在離體條件下可能不發(fā)揮抗哇巴因心臟致心律失常作用,在體條件下可對(duì)抗哇巴因致室性心律失常作用,但加重哇巴因?qū)е碌膫鲗?dǎo)阻滯。2.哇巴因抑制離體大鼠心臟收縮及舒張功能不僅存在著量反應(yīng)量-效關(guān)系(GDRR),也存在著明確的時(shí)反應(yīng)量-效關(guān)系(TDRR)。
[Abstract]:Objective 1. To observe the effect of metoprolol on arrhythmia induced by ouabain in rats, and to explore the mechanism of 尾 -blocker used in digitalis intoxication. The isolated cardiac perfusion system of langendorff was used. The time-response dose-effect relationship between ouabain and dose-response relationship in isolated rat heart was observed and analyzed. Methods: 1. Using Langendorff perfusion device, normal SD rats were randomly divided into 5 groups: normal control group. Ouabain model group and metoprolol intervention group (40 渭 mol/L and 100 渭 mol/L), 8 animals in each group, recorded the number of spontaneous ventricular premature systolic PVB, the incidence of ventricular tachycardia and ventricular fibrillation in each group during the fixed time after injection of ouabain. The recording time was 60 minutes. 2. The normal SD rats were randomly divided into 5 groups: normal control group, ouabain model group, and 0.4 mg / kg / kg 2 mg / kg metoprolol group with 8 animals in each group. To observe the time of occurrence of various arrhythmias, such as VPV, VTT, BBBV) and cardiac arrest (CAA), and to calculate the cumulative dosage of ouabain. 3. To carry out the in vitro cardiac perfusion test with Langendorff perfusion device. Ouabain was allocated to 3 渭 mol / L 10 渭 mol / L ~ 30 渭 mol / L ~ 30 渭 mol / L ~ 100 mol / L ~ 100 mol / L ~ 100 mol / L ~ 100 mol / L ~ (-1) L ~ (-1) L ~ (-1) L ~ (-1) 路L ~ (-1) 路L ~ (-1). The changes of LVDPDP) and LVEDP) of left ventricular development pressure and left ventricular end-diastolic pressure were recorded in each concentration group for 30 minutes. Results 1. In isolated heart perfusion experiment, the left ventricular end-diastolic pressure (LVDP) and left ventricular end-diastolic pressure were recorded. The number of PVB, the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF) in each group within 60 minutes were counted. There was no significant difference in arrhythmia between metoprolol intervention group and ouabain model group. Metoprolol prolonged the onset of ouabain induced ventricular arrhythmias (biphasic, short array and persistent ventricular tachycardia), but ouabain-induced block (bundle branch block and atrioventricular block) was earlier. The incidence of ventricular fibrillation was significantly reduced, and the survival time of animals was prolonged .3.The results of analysis of systolic function showed that ouabain increased the inhibition rate of LVDPs and shortened the latency with increasing concentration of ouabain at 1000 渭 mol 路L ~ (-1) 路L ~ (-1). The peak time was prolonged at low concentration of 30 渭 mol 路L ~ (-1), while 100 渭 mol / L of high concentration was shortened, and the average inhibition rate was increased. In the analysis of diastolic function, it was found that ouabain increased the maximum amplitude of left ventricular end-diastolic pressure (LVEDPP) with increasing concentration of 31000 渭 mol 路L ~ (-1) 路L ~ (-1) 路L ~ (-1) 路L ~ (-1). With the increase of concentration, the incubation period was shortened, the peak time was prolonged, and the average rate of increase was increased. Conclusion: 1. Ouabain can induce arrhythmia steadily in isolated perfused heart and in vivo. Metoprolol may not play an antiarrhythmic effect on ouabain heart in vitro, but it can antagonize the ventricular arrhythmia induced by ouabain in vivo. However, the inhibition of systolic and diastolic function of isolated rat heart by ouabain was aggravated by ouabain. There was not only a dose-response dose-effect relationship, but also a definite time-response dose-effect relationship.
【學(xué)位授予單位】：山西醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R54

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