RAT DILATED CARDIOMYOPATHY AFTER AUTOIMMUNE GIANT-CELL MYOCARDITIS

One of the possible causes of dilated cardiomyopathy is considered to be a sequel to myocarditis. Two mechanisms have been proposed in the process of progression of myocarditis into dilated cardiomyopathy: one is a persistent viral infection, and the other is an autoimmune myocardial injury. To clarify the possible part played by the autoimmune mechanism in the process, using an animal model, we investigated whether autoimmune myocarditis, exclusively not related to viral infection, might develop into dilated cardiomyopathy. Experimental autoimmune myocarditis was elicited in Lewis rats by immunization with cardiac myosin fraction. Rats of the control group were immunized with ovalbumin. The clinical course was observed over 4 months. Six rats from the myosin-immunized group died during the acute phase and the healing phase, and all those rats had severe myocarditis. All rats that survived until the end of the study showed enlarged and discolored hearts. Aneurysmal changes were observed in the right ventricle during thoracotomy. The ratio of heart weight to body weight of the myosin-immunized group was significantly higher than that of the control group (3.36+/-0.49 versus 2.69+/-0.06 g/kg, respectively; P<.005). The lengths of the anterior interventricular fissure and the posterior interventricular fissure of the hearts of the myosin-immunized group were significantly longer than those of the control group. The external diameter of the left ventricle of the myosin-immunized group was also significantly larger than that of the control group. Diffuse myocardial muscle loss and replacement fibrosis were the prominent histological findings of the rats of the myosin-immunized group. Inflammatory cell infiltrations disappeared from the majority of the lesions, but focal accumulations of mononuclear cells were rarely detected in the periphery of the lesions. When rats were immunized again 4 months after the initial immunization, severe myocarditis recurred in all these rats. Autoimmune giant cell myocarditis in the rat was demonstrated to develop into recurrent forms of myocarditis and to lead to dilated cardiomyopathy. This is a new model for postmyocarditis dilated cardiomyopathy not related to viral infection.