在過去數十年來，心血管疾病一直是位居世界前三大死因之一，其中心臟衰竭的成長速度更是逐年上升。心臟衰竭的定義為當心臟功能受損且無法持續提供身體代謝所需的一種病理狀態。心臟肥大，是指當心臟受到外來刺激時，心肌細胞為了適應以及抵抗外力而透過增加細胞本身的長度或寬度來進一步提供心臟更強的推動力和減低外力在心壁造成的張力，但它常常演進為心臟衰竭。引起心臟肥大的主要因素是機械力刺激的參與而誘導心肌細胞改變長度，其中機械力的來源可分為兩種，分別是壓力過度承載以及體積過度承載。左心室肥厚的主要成因是壓力過度承載所造成的，且往往到最後都會走向心衰竭。在我們先前的研究結果中已經成功建立透過在蘭嶼迷你豬的腹主動脈進行窄縮而誘導腹主動脈瘤(AAA)形成的模型。因此我們的假設是:在腹主動脈進行一個較長時間的窄縮會增加主動脈的阻力，進一步導致左心室的壓力過度承載，最終導致心臟衰竭的發生。一開始，在血壓測量的部分我們同時使用血壓帶與veriQ transit time flow系統進行血壓紀錄。在血壓帶的測量結果中，收縮壓以及舒張壓在窄縮12周的組別都有顯著上升。我們亦使用veriQ transit time flow的系統測量頸動脈及股動脈的血壓，頸動脈的血壓在窄縮後並無顯著上升，而股動脈血壓則是在窄縮後脈壓皆呈現下降趨勢，且在窄縮後第8周有顯著差異。為了檢驗心臟功能在腹主動脈窄縮(AAC)後是否受到影響，我們透過veriQ transit time flow系統分析了心跳速率(HR)、心搏輸出量(SV)以及心輸出量(CO)並使用Doppler Echocardiography分析左心室的短軸縮短率(FS)。其結果顯示窄縮組的心臟功能與對照組並無顯著差異，但是在窄縮12周的組別，顯示心搏輸出量呈現下滑的趨勢，相反的，心跳速率則有增加的趨勢。初步的結果顯示，左心室的短軸縮短率在窄縮12周組較對照組有下降的趨勢。為了進一步分析腹主動脈窄縮是否會誘導心臟肥大，我們對心臟重量以及心室壁(左心室、心室間隔、右心室)的厚度進行了測量分析。結果顯示，窄縮組的心臟重量以及心室壁的厚度(皆以右心室為基準)與對照組並無顯著差異。進一步以蘇木素-伊紅(H&E)染色、麥胚凝集素(WGA)和肌凝蛋白重鏈(MHC)免疫螢光染色偵測心臟細胞是否肥大。結果顯示，心肌細胞的截面積以及細胞核密度上並無顯著差異。此外，Masson’s trichrome的染色結果顯示窄縮12周並未導致左心室的纖維化。在心臟肥大相關的指標蛋白部分，我們偵測了包含心室肌凝蛋白輕鏈2(MLC2v)的磷酸化以及Rho相關激酶(ROCK)的活化。結果並沒有檢測到顯著差異，但ROCK的活化在窄縮後12周有上升的趨勢。為了檢驗腹主動脈窄縮是否誘發心室的重塑反應，我們對熱休克蛋白(HSP)的家族成員(包含HSP40、HSP70和HSP90)進行基因表達的分析。結果顯示在窄縮後12周，HSP40 mRNA顯著上升，HSP70與HSP90則無明顯變化。綜合上述結果，腹主動脈窄縮12周不僅會造成血壓的上升，並開始影響心臟功能。若加長腹主動脈窄縮的時間應可偵測到心臟肥大的顯著變化。

Cardiovascular disease is among the top three causes of mortality in the world, with heart failure representing the fastest growing subclass over the past decade. Heart failure is defined as the pathologic state of impaired cardiac function rendering the heart unable to maintain an output sufficient for the metabolic need of the body. Cardiac hypertrophy in which myocytes grow in length and/or width as a means of increasing cardiac pump function and decreasing ventricular wall tension often precedes heart failure. A major contributing factor for cardiac hypertrophy is mechanical stress which induces cardiomyocytes to grow in length upon the pressure or volume overload. Left ventricular hypertrophy (LVH) is the major consequence of pressure-overload and often leads to heart failure. Our laboratory has established a coarctation-induced abdominal aortic aneurysm model by surgically narrowing an infrarenal abdominal aortic segment of Lanyu mini pigs. We hypothesized that prolonged coarctation of the abdominal aorta increases aortic resistance, causes pressure overload of the left ventricle, and eventually leads to heart failure. Blood pressure (BP) was measured with both cuff method and veriQ transit time flow system. Using cuff method, both systolic and diastolic BP increased significantly at 12 weeks post-coarctation. Using transit time flow system, BP was measured at both carotid and femoral arteries. The BP of the carotid artery did not change significantly after coarctation whereas the pulse pressure of the femoral artery exhibited the trend to decrease and was significant at 8 weeks post-coarctation. To examine whether abdominal aorta coarctation (AAC) affects cardiac functions, we analyzed heart rate, stroke volume and cardiac output by transit time flow system and fractional shortening by Doppler echocardiography. No significant differences in stroke volume, heart rate or cardiac output were detected between the AAC and sham groups, but the 12w-AAC group tended to exhibit decreased stroke volume and increased heart rate. Preliminary results showed that 12w-AAC group exhibited decreased fractional shortening compared to sham group. To examine whether AAC induces cardiac hypertrophy, heart weight, wall thickness of the LV, right ventricle (RV), and the interventricular septum were measured. No significant difference was detected with apparent increases in the septum wall thickness (normalized with the RV wall) in the 12w-AAC group. Cellular hypertrophy was assessed with hematoxylin-and-eosin staining, Wheat Germ Agglutinin (WGA), and myosin heavy chain (MHC) immunofluorescence. No change in the cardiomyocyte cross-sectional area or nuclear density was detected. In addition, no tissue fibrosis in the LV was detected with masson’s trichrome staining. Cardiac hypertrophy markers, including phosphorylation of the ventricular myosin light chain 2 (MLC2v) and the activation of Rho-associated kinases (ROCK), were also examined. No significant difference was detected but ROCK activation tended to increase in the 12w-AAC group. To examine whether cardiac remodeling occurs after AAC, gene expression of the heat shock protein (HSP) family members, HSP40, HSP70, and HSP90, was examined. HSP40 mRNA was up-regulated in the 12w-AAC group while the other two did not change. Taken together, these results show that prolonged AA coarctation for 12 weeks increases blood pressure and starts to affect cardiac function. Longer time period of AA coarctation may be needed to detect significant changes associated with cardiac hypertrophy.

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