Fumiaki Masani

A novel experimental model of giant cell myocarditis induced in rats by immunization with cardiac myosin fraction

It is suspected that autoimmune disease processes are involved in the pathogenesis of a part of giant cell myocarditis. However, evidence for autoimmunity has rarely been demonstrated in clinical investigations. In this study, we have demonstrated a new animal model of autoimmune myocarditis characterized by the appearance of multinucleated giant cells. Lewis rats were immunized twice with human cardiac myosin fraction in complete Freunds adjuvant. Cardiac myosin fraction was prepared from the ventricular muscle of human hearts. Three weeks after the first immunization, acute and severe myocarditis was elicited in all rats. This myocarditis was characterized by massive pericardial effusion, enlargement of the heart, and gray discoloration of the cardiac muscle. Microscopically, there was marked cellular infiltration consisting of mononuclear cells, neutrophils, fibroblasts, and a considerable number of multinucleated giant cells. Extensive myocardial necrosis was also present. The heart weights increased from the third week to the fourth week and then gradually decreased. The titer of anti-myosin antibodies began to elevate from the second week and remained high until the sixth week. In the sixth week, inflammation became smoldering and the multinucleated giant cells disappeared. These findings indicate that the cardiac myosin fraction contains myocarditogenic antigen and that giant cell myocarditis can be induced by autoimmune involvement. To our knowledge, this is the first report of experimental giant cell myocarditis, which is closely similar to human giant cell myocarditis in its histology and clinical course.

Effects of cyclosporine, prednisolone and aspirin on rat autoimmune giant cell myocarditis

OBJECTIVES Preventive effects of cyclosporine, prednisolone and aspirin on autoimmune giant cell myocarditis in rats were investigated. BACKGROUND The therapeutic efficacy of immunosuppressants for human myocarditis is controversial. Although harmful effects of immunosuppressive therapy on experimental viral myocarditis have been reported, the effects on autoimmune myocarditis have not been investigated. Recently, a novel experimental autoimmune myocarditis model characterized by congestive heart failure and multinucleated giant cell has been established. Using this model, the preventive effects of cyclosporine, prednisolone and aspirin on autoimmune myocarditis were investigated. METHODS Lewis rats were immunized with cardiac myosin in complete Freunds adjuvant on days 0 and 7. In experiment 1, four groups of seven rats each were established. Rats in each group received for 21 days intraperitoneal injections of either 1) phosphate-buffered saline solution, 1 ml/day (control); 2) cyclosporine, 20 mg/kg body weight per day (cyclosporine 20); 3) prednisolone, 4 mg/kg per day; or 4) aspirin, 15 mg/kg per day. In experiment 2, two additional groups (five rats each) received for 21 days an injection of cyclosporine, 1 or 5 mg/kg per day (cyclosporine 1 and cyclosporine 5, respectively). All rats were killed on day 21, when histopathologic studies were performed and the titers of antimyosin antibodies were measured. RESULTS The rats in the control, prednisolone and aspirin groups became ill and immobile in week 3. In comparison, rats in the cyclosporine 5 and 20 groups were still active until death was induced. Heart weight/body weight, lung weight/body weight and liver weight/body weight ratios in the rats in the cyclosporine 5 and cyclosporine 20 groups were significantly lower than those in the control group, and no differences were detectable among rats in the control, prednisolone and aspirin groups. The rats in the latter three groups and the cyclosporine 1 groups showed severe myocarditis with multinucleated giant cells. However, myocarditis was effectively prevented in the rats in the cyclosporine 5 and 20 groups. The histologic scores in each group were 2.91 in the control group, 2.14 in the prednisolone group, 2.91 in the aspirin group and 0.02, 2.58 and 0.07, respectively, in the cyclosporine 20, 1 and 5 groups. Production of antimyosin antibodies was remarkably suppressed in rats in the cyclosporine 5 and 20 groups in comparison with values in all other groups. CONCLUSIONS Autoimmune myocarditis is preventable by cyclosporine but not by prednisolone or aspirin in usual dosages.

Cardiac Sarcoidosis 67Ga Imaging and Histology

A 23-year-old man was admitted to Niigata Prefectural Shibata Hospital in September 1992 because of sustained ventricular tachycardia and cardiogenic shock. After cardioversion of the ventricular tachycardia, his ECG showed sinus rhythm, left axis deviation, complete right bundle branch block, and left anterior fascicular block. The cardiac …

Ethanol Ingestion on Allylamine-Induced Experimental Subendocardial Fibrosis

Effects of ethanol ingestion on allylamine-induced subendocardial fibrosis of the myocardium and intimal hyperplasia of the intramyocardial coronary artery were investigated in male Wistar rats. The toxic effect of allylamine is ascribed to acrolein produced from allylamine by benzylamine oxidase. Animals were forced to drink allylamine solution for 12 weeks. Incidence and size of subendocardial fibrosis were examined, and the lesions of the intramyocardial artery were scrutinized. Effects of ethanol on the systemic blood pressure and benzylamine oxidase activity were investigated in another experiment. Treatment with allylamine resulted in subendocardial fibrosis (size = 4.2%) in 4 of 12 rats. The incidence of fibrosis was increased (up to 6/12) and the area of fibrosis was augmented (to 6.8%) in animals additionally treated with epinephrine. The lesions in the intramyocardial vasculature were also augmented. Ethanol ingestion reduced allylamine-induced subendocardial fibrosis and intramyocardial coronary lesions. The effects were significant in animals additionally treated with epinephrine. Systemic blood pressure and benzylamine oxidase activity were not significantly affected by allylamine or by ethanol. The vasodilatory effect of ethanol may have prevented the development of microvascular spasm induced by allylamine.

A case of giant cell myocarditis with evidence of cardiac autoimmunity

A 45-year-old-woman with giant cell myocarditis showing high titer of circulating antiheart antibodies is reported. She experienced two recurrences of myocarditis and repeatedly responded to immunosuppressive therapy using prednisolone. The titer of antiheart antibodies went up and down appropriately according to the clinical responses to immunosuppressive therapy. This case suggested that giant cell myocarditis might be related to autoimmunity.

Effect of Ethanol on Allylamine-Induced Subendocardial Fibrosis

In view of the epidemiologic observations that a moderate consumption of ethanol reduces cardiac death and total death, an attempt was made to elucidate the mechanism of the beneficial effect of ethanol using male Wistar rats and spontaneously hypertensive rats (SHR). As a model of ischemic myocardial derangement, allylamine-induced subendocardial fibrosis was chosen. Animals were divided into four groups and were forced to take one of the following four solutions ad libitum: allylamine (group A), allylamine + ethanol (group AE), ethanol (group E), and water (group C). To augment the workload on the heart, each group of Wistar rats was divided into two subgroups, and in one epinephrine was additionally injected (200(μg/kg subcutaneous, three times per week). Subendocardial fibrosis was noted in 5 out of 12 in group A of Wistar rats not treated with epinephrine. The incidence of fibrosis was greater in animals additionally treated with epinephrine, being found in 8 out of 12 Wistar rats. The incidence of fibrosis was further enhanced in SHR (7 of 8). Thus, allylamine-induced subendocardial fibrosis was augmented when the energy requirement of the heart was increased by increased workload. No subendocardial fibrosis was noted in Wistar rats belonging to group AE, even with additional treatment of epinephrine. The beneficial effect was not observed in SHR. It is postulated that the augmentation of subendocardial fibrosis is due to augmentation of ischemia, and ethanol produces preventive effects by alleviating ischemia through improvement of the coronary microcirculation.