动物肥厚性心肌病——人类疾病理想模型

Animal Hypertrophic Cardiomyopathy:Ideal Model of Human Disease

动物肥厚性心肌病的临床所见、心脏超声波图、肉眼组织病理、冠状小动脉变化、胶原纤维组织变化等 ,与人类肥厚性心肌病非常相似 ;遗传学分析 ,人类及猫肥厚性心肌病均为家族性常染色体显性遗传类型。动物肥厚性心肌病可为理想模型来研究人类疾病 ,而且动物肥厚性心肌病小冠状动脉病变与人类冠状动脉粥样化血管切除或皮下血管内腔扩张术后小冠状动脉再阻塞相同 ,可为人类疾病之模型。尤其猪心脏血行、生理及形态均与人类心脏相似 ,故猪肥厚性心肌病实为人类肥厚性心肌病研究之理想动物模型。

A spontaneously occurring disease of domestic cats,dogs,and pigs was identified by echocardiography and was strikingly similar in its phenotypic expression to hypertrophic cardiomyopathy(HCM) in humans.It was characterized by unexplained left ventricular hypertrophy in variety of patterns with or without evidence of outlow obstruction.Affected cats did not have phenotypic evidence of HCM before 6 months of age,developed HCM during adolescence and developed severe HCM during young adulthood as in humans.Papillary muscle hypertrophy that produced midcavity obstruction and systolic anterior motion of the mitral valve was the most consistent manifestation of HCM.Genetic study when affected cats were bred affected cats,45% of the cats were affected,22% of cats unaffected,and 33% cats were still born.Offspring from breeding affected to unaffected cats,55% of cats were affected.Findings were consistent with an autosomal dominant pattern of inheritance with 100% penetrance,with the stillborns representing lethal homozygotes that died in utero.The familial HCM in Maine Coon cats closely resembles the human form of familial HCM.Morphologic features of spontaneously occurring HCM were compared in 35 humans,53 cats,10 dogs,and 55 pigs.Asymmetric hypertrophy of the ventricular septum,marked disorganization of cardiac muscle cells,abnormal intramural coronary arteries and myocardial fibrosis were each present in the ventricular septum of human,feline,canine and porcine forms of HCM;these abnormalities were generally more severe and most frequently identified in humans.Asymmetric left ventricular hypertrophy(based on the calculated septal-to-free wall thickness ratio) was most common in humans 81%,dog 80%,cats 31%,and pigs 45%;P<0.01.with HCM in all 4 species,hypertrophy was often diffuse,involving substantial portions of the anteriolateral and posterior free walls,and the ventricular septum.Marked septal disorganization(≤5% of the tissue section) was observed in 92% patients,but in only 27% cats,20% dogs,and 45% pigs(P<0.001).Abnormal intramural coronary arteries occurred with similar frequency in the ventricular septum of 66% patients,74% cats,60% dogs,and 84% pigs (P<NS).Moderate to severe septal fibrosis was identified more commonly in humans(39%) and pigs(47%) than in cats and dogs(21%);(P<0.001),In all 4 species abnormal intramural coronary arteries were most commonly observed within or at the margins of areas of fibrosis.These morphologic findings describe spontaneously occurring models of HCM in cats,dogs,and pigs with substantial structural similarities to the well-recognized disease entity in humans.The wall thickening with narrow lumen included extensive proliferation of smooth muscle cells contractive or synthetic forms and pericytes in the intima and media with disrupted or fragmentated elastic lamella was observed more commonly in the intramural coronary arteries of pigs with HCM.This intramural coronary arterial abnormality is an important lesion that develops restenosis of coronary arteries after percutaneous translumainal coronary angipleasty or by pass in human with atherosclerosis.Pigs with HCM,characterized by spontaneously occurring lesions in the intramural coronary arteries,may provide a good animal model for human intramural coronary arterial disease.