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TWA在急性心肌缺血心律失常中的作用機制及其預(yù)防和治療

發(fā)布時間:2018-12-25 08:15
【摘要】:目的:TWA可以預(yù)測心肌梗死心律失常的發(fā)生,但其機制沒有統(tǒng)一的認識。本實驗通過給予雷諾嗪、蘭尼堿、維拉帕米,進一步探討急性心肌缺血時TWA的機制,并為臨床預(yù)防和治療急性心肌缺血心律失常提供依據(jù)。 方法:50只日本大耳白兔隨機分為正常組、缺血組、雷諾嗪組、蘭尼堿組、維拉帕米組,并制備左心室楔形心肌塊。雷諾嗪為晚鈉通道抑制劑,蘭尼堿為RyR2受體阻滯劑,維拉帕米為鈣通道阻滯劑。采用玻璃微電極,同步記錄心肌內(nèi)、外膜跨膜動作電位、跨壁的心電圖及其心肌收縮力。觀察雷諾嗪、蘭尼堿及維拉帕米對TWA及心律失常的影響。 正常組給予持續(xù)臺氏液灌注,缺血組在給予灌注臺氏液穩(wěn)定1小時后,停止灌注臺氏液20分鐘,然后誘發(fā)TWA的發(fā)生,雷諾嗪組、蘭尼堿組及維拉帕米組在灌注臺氏液穩(wěn)定1小時后分別給予含有雷諾嗪、蘭尼堿、維拉帕米的臺氏液預(yù)灌注,然后停止灌注含有雷諾嗪、蘭尼堿、維拉帕米的臺氏液20分鐘,分別誘發(fā)TWA的發(fā)生。兔的左心室楔形心肌塊在基礎(chǔ)狀態(tài)下給予1000ms步長持續(xù)刺激,停止灌注臺氏液或含有上述藥物的臺氏液20分鐘后給予200ms的步長刺激誘發(fā)TWA并觀察心律失常的發(fā)生。 結(jié)果:與正常組比較,缺血組TWA及心律失常的發(fā)生明顯增加。正常組無TWA及心律失常的發(fā)生;與正常組比較,缺血組中10/10的產(chǎn)生TWA,5/10的產(chǎn)生心律失常。與缺血組相比,維拉帕米組中TWA及心律失常的發(fā)生明顯減低,在維拉帕米組中無TWA及心律失常的發(fā)生。與缺血組相比,雷諾嗪組中TWA及心律失常的發(fā)生明顯增加,在雷諾嗪組中10/10的發(fā)生TWA,10/10的發(fā)生心律失常。蘭尼堿組與缺血組相比,TWA及心律失常的發(fā)生無明顯差異,,在蘭尼堿組中8/10發(fā)生TWA,4/10的發(fā)生心律失常。 結(jié)論:鈣通道阻滯劑維拉帕米可以抑制TWA及心律失常的發(fā)生,這說明鈣離子紊亂是急性心肌缺血TWA發(fā)生的重要機制。
[Abstract]:Objective: TWA can predict arrhythmias in myocardial infarction, but the mechanism is not uniform. In this study, the mechanism of TWA in acute myocardial ischemia was further investigated by the administration of ranolazine, lannitine and verapamil, and the basis for clinical prevention and treatment of acute myocardial ischemia arrhythmias was provided. Methods: fifty Japanese white rabbits were randomly divided into three groups: normal group, ischemia group, ranosin group, ranidine group and verapamil group. Ranolazine was used as a late sodium channel inhibitor, lannitine as a RyR2 receptor blocker and verapamil as a calcium channel blocker. The transmembrane action potential, transmural electrocardiogram (ECG) and contractility of myocardium were recorded simultaneously by glass microelectrode. The effects of ranolazine, raniline and verapamil on TWA and arrhythmia were observed. The normal group was perfused with continuous Tetranyl solution, the ischemia group stopped the infusion of Tetranyl solution for 20 minutes after the infusion of Tetranyl solution was stabilized for 1 hour, then the occurrence of TWA was induced in Renolazine group. After one hour of steady infusion of Tyrlozin solution, the Ranifen group and the verapamil group were preperfused respectively with Renolazine, Rannitine, verapamil, and then stopped infusing the Tetrandrine solution containing Renolazine, Lannidine and verapamil for 20 minutes, respectively. TWA was induced respectively. The rabbit left ventricular wedge block was stimulated with 1000ms step in basal state, and the TWA was induced by the step stimulation of 200ms 20 minutes after stopping the infusion of Tetranyl solution or Tetrachlor solution containing the above mentioned drugs, and the occurrence of arrhythmia was observed. Results: compared with the normal group, the incidence of TWA and arrhythmia increased significantly in ischemic group. There was no TWA and arrhythmia in normal group, and 10 / 10 of TWA,5/10 was produced in ischemic group. The incidence of TWA and arrhythmia in verapamil group was significantly lower than that in ischemic group, but no occurrence of TWA and arrhythmia was found in verapamil group. Compared with ischemic group, the incidence of TWA and arrhythmia increased significantly in Renolazine group, and TWA,10/10 arrhythmias occurred in 10 / 10% of Renolazine group. There was no significant difference in the occurrence of TWA and arrhythmias between the Lannidine group and the ischemic group. The incidence of TWA,4/10 arrhythmias occurred in 8 / 10 of the Lanni base group. Conclusion: verapamil, a calcium channel blocker, can inhibit the occurrence of TWA and arrhythmias, which suggests that calcium disturbance is an important mechanism of acute myocardial ischemia TWA.
【學(xué)位授予單位】:華中科技大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2013
【分類號】:R542.22

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