本文選題：無癥狀舒張功能不全 + 壓力超負荷��； 參考：《中國人民解放軍軍醫(yī)進修學院》2007年碩士論文

【摘要】： 目的：無癥狀舒張功能不全(Asymptomatic Diastolic Dysfunciton，ADD)是指舒張功能異常、射血分數正常，不伴有心衰的癥狀和體征。ADD患者由于無明顯癥狀，因此臨床上往往忽視這部分患者，相關研究和報道也較少。故本研究通過新西蘭兔腹主動脈縮窄術，模擬人類高血壓誘導的ADD的病理生理特點，建立人類高血壓誘導的ADD的動物模型，采用超聲心動圖、血流動力學、血清和心肌局部神經內分泌水平、組織形態(tài)學等多項指標綜合評價模型的病理生理特點。并在術后第二日給予倍他樂克，觀察其治療效果。 方法：健康雄性新西蘭兔47只，隨機分為假手術組(n=15)、手術組(n=32)。手術組在雙側腎動脈分支下方1cm處行腹主動脈縮窄術(外徑縮窄35～40％)；假手術組作為正常對照組。術后觀察兔精神狀態(tài)、飲食、活動、體重等指標變化。分別于術前和處死前行血流動力學檢查檢測心臟功能的變化，于術前、術后2周、4周、8周行超聲心動圖檢查動態(tài)監(jiān)測心臟結構和功能的變化。酶聯(lián)免疫吸附法(Elisa)檢測各個階段血清(0、2、4、8周)和心肌中血管緊張素Ⅱ(AngⅡ)、內皮素-1(ET-1)、去甲腎上腺素(NE)和腦型利尿鈉肽前體氨基端肽(NT-proBNP)和尿素酶法檢測血清尿素氮(BuN)和肌酐(Cr)變化。HE染色觀察心肌形態(tài)學改變。其中超聲檢查包括M超測量左室室壁厚度、左室內徑，用2切面改良Simpson法測量左室容積、左室射血分數(LVEF)；用脈沖多普勒測量二尖瓣血流頻譜E峰、A峰、E峰減速時間(decelerating time，DT)、A峰持續(xù)時間(A duration，AD)，右上肺靜脈收縮期S波(PVs)、肺靜脈舒張期D波(PVd)、左房收縮逆向a波時間(PVa duration，，PVaD)；用彩色M型獲取舒張早期左室內血流播散速度(early diastolic flow propagation velocity，Vp)；用組織多普勒(tissue Doppler imaging，TDI)在二尖瓣環(huán)室間隔、側壁、下壁、前壁4處測量心肌長軸方向的收縮期峰速(Sm)、舒張早期峰速(Em)、舒張晚期峰速(Am)和等容舒張時間(isovolumic relaxation time，IVRT)等值，計算E／Em、E／Vp等參數。血流動力學檢查包括左室收縮壓(LVSP)、左室舒張末壓(LVEDP)、壓力最大上升速率(+dp／dt_(max))、壓力最大下降速率(-dp／dt_(max))、等容舒張期松弛時間常數(τ)等指標變化。2)將NT-proBNP與EF、Vp、sm、Em、E／Em和E／Vp行相關分析。3)雄性新西蘭兔24只隨機分為假手術組(n=8)、ADD組(n=8)和ADD+藥物治療組(n=8)。藥物治療組于術后第二日給予倍他樂克(25mg，2／日)，觀察8周，檢測指標同前。 結果：1)術后7～8周，部分手術組兔出現(xiàn)食欲不振和活動量減少，但均未出現(xiàn)呼吸困難、肺Up音等明顯心衰的癥狀；而假手術組兔未出現(xiàn)任何臨床癥狀和體征。2)與假手術組相比，術后2周IVSD、LVPWD、LVmass增加(P＜0.000)；4周時肥厚增加更加明顯，Em降低(P＜0.05)、E／Vp增加(P＜0.05)；8周時LAV、LVEDD、LVEDV增加(P＜0.05)；Sm(P＜0.01)、Em(P＜0.01)、Vp(P＜0.000)均降低，E／Em(P＜0.05)、E／Vp(P＜0.000)增加。而EF始終保持正常。血流動力學檢查測定LVEDP增高(P＜0.01)，τ值延長(P＜0.01)。病理檢查提示心肌細胞肥大。8周時血清AngⅡ、ET-1、NE、NT-proBNP水平均顯著升高(P＜0.000)，心肌AngⅡ(P＜0.000)、ET-1(P＜0.05)、NE和NT-proBNP(P＜0.01)也升高。3)NT-proBNP與Sm、Em、E／Em和E／Vp均顯著相關，而與EF相關性差。4)倍他樂克治療組LVEDP(P＜0.000)、τ(P＜0.05)、IVSD(P＜0.05)、Em(P＜0.05)和E／Vp(P＜0.05)等均明顯改善；血清AngⅡ(P＜0.01)、ET-1(P＜0.05)、NE和NT-proBNP(P＜0.05)也顯著降低。心肌中AngⅡ、ET-1、NE和NT-proBNP均下降(P＜0.05)。 結論：1)通過縮窄新西蘭兔腎下腹主動脈(縮窄比例為35％～40％)，8周時舒張功能受損、射血分數正常而且無明顯心衰癥狀。觀察16周后超聲和血流動力學指標均未發(fā)生明顯變化，說明該模型具有一定的穩(wěn)定性，或許可以作為人類高血壓誘導的ADD的動物模型。2)進一步通過TDI技術檢查發(fā)現(xiàn)，ADD以舒張功能受損為主，同時也伴有收縮功能的輕度損傷。3)血清和心肌中AngⅡ、ET-1、NE和NT-proBNP均升高，可能參與了舒張功能的損傷。4)NT-proBNP與反映左室舒張功能的Em、E／Em、E／Vp也存在良好的相關性，是檢出舒張功能早期損傷的敏感指標。5)倍他樂克可逆轉左室肥厚，改善血流動力學和左室舒張功能。6)倍他樂克可降低血清和心肌組織中AngⅡ、ET-1、NE和NT-proBNP水平。
[Abstract]:Objective: asymptomatic diastolic dysfunction (Asymptomatic Diastolic Dysfunciton, ADD) refers to abnormal diastolic function, normal ejection fraction, asymptomatic symptoms and signs of heart failure without symptoms and signs of.ADD patients. Therefore, this part of the patients is often neglected in clinical and less related studies and reports. Pulse constriction, which simulates the pathophysiological characteristics of ADD induced by human hypertension, establishes an animal model of ADD induced by human hypertension. It uses echocardiography, hemodynamics, serum and myocardial local neuroendocrine levels, histomorphology and other indicators to evaluate the pathophysiology of the model and give times more than second days after operation. He Lok, to observe the effect of his treatment.
Methods: 47 healthy male New Zealand rabbits were randomly divided into sham operation group (n=15) and operation group (n=32). Abdominal aorta coarctation (35 to 40%) was performed at 1cm below the bilateral renal artery branch (35 to 40%), and the sham operation group was used as a normal control group. The changes of cardiac function were detected by hemodynamic examination before operation. The changes of cardiac structure and function were monitored dynamically by echocardiography at 2 weeks, 4 weeks and 8 weeks after operation. Enzyme linked immunosorbent assay (Elisa) was used to detect serum (0,2,4,8 weeks) and myocardial angiotensin II (Ang II), endothelin -1 (ET-1), norepinephrine (N). E) and the changes of serum urea nitrogen (BuN) and creatinine (Cr) and serum urea nitrogen (BuN) and creatinine (Cr) changes with brain type diuretic natriuretic peptide (NT-proBNP) and serum urease assay. The echocardiographic examination included M ultra measurement of left ventricular wall thickness, left ventricular diameter, left ventricular volume, left ventricular ejection fraction (LVEF) with 2 cut surface improved Simpson method, and pulse multiple. E peak, A peak, E peak deceleration time (decelerating time, DT), A peak duration (A duration, AD), S wave (PVs) in the right upper pulmonary vein (PVs), pulmonary venous systolic time, and left atrial systolic time were used to measure the velocity of early diastolic blood flow in the left chamber. C flow propagation velocity, Vp); the systolic peak velocity (Sm), early diastolic velocity (Em), late diastolic peak velocity (Em), late diastolic peak velocity (Am) and equal volume diastolic time were measured by tissue Doppler (tissue Doppler imaging, TDI) at the mitral annular space, lateral wall, lower wall, and anterior wall at 4 places. Vp and other parameters. The hemodynamic examination included left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), maximum pressure rise rate (+dp / dt_ (max)), maximum pressure drop rate (-dp / dt_ (max)), equal volume relaxation time constant (tau) and other indexes changed.2) 24 rabbits were randomly divided into the sham operation group (n=8), the ADD group (n=8) and the ADD+ drug treatment group (n=8). The drug treatment group was given Betaloc (25mg, 2 / day) on the second day after the operation and was observed for 8 weeks.
Results: 1) 1) 7~8 weeks after the operation, there was no appetite and less activity in the rabbits in the operation group, but there was no symptom of dyspnea, lung Up sound and other symptoms of heart failure, while the rabbits in the sham operation group had no clinical symptoms and signs.2), compared with the sham operation group, 2 weeks after the operation, IVSD, LVPWD, LVmass increased (P < 0), and the hypertrophy increased more clearly at 4 weeks. Em decreased (P < 0.05), E / Vp increased (P < 0.05); LAV, LVEDD, LVEDV increased at 8 weeks (P < 0.05); Sm (P < 0.01), Em (0) decreased. Serum Ang II, ET-1, NE, NT-proBNP water increased significantly at.8 weeks (P < 0), Ang II (P < 0), ET-1 (P < 0.05), NE and NT-proBNP (< 0.01). P < 0.05) and E / Vp (P < 0.05) were significantly improved, and serum Ang II (P < 0.01), ET-1 (P < 0.05), NE and NT-proBNP (P < 0.05) were also significantly reduced.
Conclusion: 1) by narrowing the lower abdominal aorta of New Zealand rabbits (the proportion of coarctation is 35% to 40%), the function of Shi Shuzhang is damaged in 8 weeks, the ejection fraction is normal and there is no obvious heart failure symptoms. There is no obvious change in the ultrasonic and hemodynamic indexes after 16 weeks, which indicates that the model has a certain stability and may be used as human hypertension. The induced ADD animal model.2) further through the TDI technique examination, it was found that ADD was mainly diastolic dysfunction, accompanied by a mild injury of.3) in.3) serum and Ang II, ET-1, NE and NT-proBNP in the myocardium, and may be involved in the diastolic function of.4) NT-proBNP and the left ventricular diastolic function. In good correlation,.5 is a sensitive indicator of early diastolic dysfunction. Betaloc can reverse left ventricular hypertrophy, improve hemodynamics and left ventricular diastolic function.6) Betaloc can reduce the level of Ang II, ET-1, NE and NT-proBNP in serum and myocardial tissue.

【學位授予單位】：中國人民解放軍軍醫(yī)進修學院
【學位級別】：碩士
【學位授予年份】：2007
【分類號】：R-332;R96

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