Echocardiography in Pigs with Hypertrophic Cardiomyopathy: Establishment and Application
Date Issued
2006
Date
2006
Author(s)
Lin, Jyh-Hung
DOI
zh-TW
Abstract
Animal models play important roles in biomedical researches, providing valuable experimental information for clinical applications. Apart from primates, the pig is the mammal most similar to humans in the terms of the structure and function of its cardiovascular system. Thus, pig models play vital roles in the research into cardiovascular diseases. Cardiovascular diseases are major causes of human death. Using pig models in cardiovascular disease research can facilitate the progress of human medicine and improve human health. Hypertrophic cardiomyopathy (HCM) is one of the most important human cardiovascular diseases. The typical pathological changes of HCM include hypertrophy of cardiac muscle, myocardial fibrosis, intramural coronary artery disease (IMCAD) and myocardial disorientation. This investigation establishes of echocardiography in diagnosing porcine HCM to screen HCM pigs for breeding, and ulilizes pig models tostudy the relationship between IMCAD lesion in HCM and cardiac functions.
The experimental results demonstrate that pigs with HCM show a significantly increase in the thickness of ventricular septum and a decrease in the left ventricular function. The systolic anterior motion and blood flow velocity increase caused by the obstraction of left ventricular outflow tract is observed in the severe cases of HCM. These echocardiographic results resemble the diagnostic results of human clinical medicine. Pathological examination also displays the symptoms of myocardial fibrosis, IMCAD and myocardial disorientation in pigs with HCM. A comparison of the clinical and pathological analysis of human HCM in the literature with the results of this study confirm that the results of clinical and pathological examinations of porcine HCM were similar those in humans.
Echocardiography was utilized to investigate the thickness of the ventricular septum and the diameter of ventricular chamber of 84 pigs. The parameters of the left ventricular function, especially left ventricular ejectional fraction (LVEF) and fraction shortening (FS), were obtained. The pigs were then sacrificed and their hearts were removed for pathological examination. The pathological criteria of myocardial disorientation, myocardial fibrosis and IMCAD excluding hypertension were adopted in HCM examination. The echocardiographic examination of IVS-d greater than 15 mm was set as the clinical threshold of porcine HCM. The PPV, NPV, sensitivity , specificity and kappa value of the clinical threshold, using the pathological examination as the golden standard for porcine HCM, were 66.7 %, 94.2 %, 71.4 %, 92.9 % and 0.566, respectively.
Exploring the pathogenesis of IMCAD is useful for clarifying the relationship between the pathological lesion and the cardiac function. The IMCAD is the most common lesion in HCM pathogenesis. This study found that the function of the left ventricular function remained normal, with no obvious clinical symptom. However, the left ventricular function decreased when the severity of IMCAD increased. The percentage of intramural coronary artery lumen and left ventricular funftion decresed when the thickness of ventricular septum increased. This condition uaually leads to ischemia, increasing the proximity of sudden death. Myocardial fibrosis was also found to have increased in the heart with severe IMCAD. Additionally, the left ventricular function was also significantly decreased.
Echocardiography was also used to survey the HCM incidence of the experimental population. The experimental results indicate that the incidence of HCM increased from 8.25% (35/424) in the first generation to 14.16% (96/678) in the third generation. The HCM incidence was 8.76 % (17/194) in the control purebred line and 7.83 % (18/230) in the hybrid line. Although the incidences differed among generations, the difference was not significant (P>0.05). The results also reveal that the incidence increased as the age of pigs increased, but did not increase further after 24 months of age. The incidence was similar to that of human HCM. Pedigree analysis showed that the porcine HCM may be inherited, and was not caused by a single gene mutation.
The following conclusions drawn from this study are: (1) echocardiography was established for porcine HCM examination, and pigs with HCM showed a significantly increase in the thickness of ventricular septum (end stage of diastolic), the criteria (IVS-d>15mm) for porcine HCM determination were confirmed using echocardiography and the PPV is 66.7 %, (2) the left ventricular function decreased when the severity of IMCAD increased, (3) the incidence of experimental pigs (14.16 %) after the breeding of three generations was higher than that of control pigs (8.25%), and (4) the porcine HCM could determinate by echocardiography at 7-8 months old, the incidence increased as the age of pigs increased, but did not increase further after 24 months of age; the mortality of HCM pigs due to unexpected death was 27.27%.
Subjects
豬
肥厚性心肌病
心臟超音波
Pigs
Hypertrophic cardiomyopathy
Echocardiography
SDGs
Type
thesis
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