| Summary: | 碩士 === 國立成功大學 === 細胞生物與解剖學研究所 === 102 === 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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