| 1. |
- Matsui, Shinobu, et al.
(author)
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Amiodarone minimizes experimental autoimmune myocarditis in rats.
- 2003
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In: European journal of pharmacology. - 0014-2999. ; 469:1-3, s. 165-73
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Journal article (peer-reviewed)abstract
- Amiodarone, a promising drug for the treatment of tachyarrythmias, was recently found to have immunomodulatory effects in vitro. We hypothesized that amiodarone would affect the immune system in vivo and examined the effect of amiodarone on myocarditis in rats. We induced experimental autoimmune myocarditis in rats by cardiac myosin immunization and treated the animals with an intraperitoneal injection of amiodarone at 25 mg/kg/every other day, 10 times after the induction of experimental autoimmune myocarditis. In the treated group, both microscopic and macroscopic examinations showed reduced heart weights, a mild and localized infiltration of inflammatory cells and fibrosis in the myocardium, and a mild congestion in the liver and lungs as compared with the control group. The phenotypic distribution of lymphocytes in peripheral blood showed a significant decrease in the CD4/CD8a ratio in the treated group, but not in the control group. The proportion of mast cells involved in inflammatory cell infiltration was lower in the treated group than the control group. In vitro, amiodarone inhibited the proliferation of mast cells by arresting them in the G2 phase of the cell cycle. These results indicated that amiodarone minimized the progression of experimental autoimmune myocarditis, suggesting a potential therapeutic role for amiodarone treatment in patients suffering from myocarditis, especially myocarditis complicated by cardiac arrhythmias. One possible mechanism by which amiodarone minimizes the progression of experimental autoimmune myocarditis may be to affect the immune system via the immunomodulatory effects on T cell and mast cell functions.
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| 2. |
- Matsui, Shinobu, et al.
(author)
-
Transfer of rabbit autoimmune cardiomyopathy into severe combined immunodeficiency mice.
- 2003
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In: Journal of cardiovascular pharmacology. - 0160-2446. ; 42 Suppl 1
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Journal article (peer-reviewed)abstract
- Growing evidence suggests that the autoimmune mechanism plays an important role in the pathogenesis of dilated cardiomyopathy. The purpose of this study was to evaluate the effect on the cardiac structure and function by the transfer of immunoglobulin G (IgG) and/or lymphocytes from rabbits immunized with a synthetic peptide corresponding to the sequence of the second extracellular loop of beta1-adrenoceptor (beta peptide) into severe combined immunodeficiency (SCID) mice. CB-17 SCID mice were injected intraperitoneally with 2 mg of IgG and/or 1 x 10(7) peripheral blood lymphocytes (PBL) from either rabbits immunized with both beta1 peptide and adjuvant (beta group), and adjuvant or rabbits with adjuvant only (N group). Thirty-five SCID mice were divided into seven groups: (1) N-IgG group; (2) N-PBL group; (3) N-IgG+PBL group; (4) beta-IgG group; (5) beta-PBL group; (6) beta-IgG+PBL group; and (7) control group. Morphological, serological and endocrinological studies were performed 70 days after the transfer. Results showed that heart weight and heart weight/body weight ratio in the beta-IgG+PBL group tended to be increased as compared with those in other groups. All mice in the beta-IgG group, two in the beta-PBL group and four in the beta-IgG+PBL group showed high titer of rabbit anti-beta1-adrenoceptor antibodies. Brain natriuretic peptide in the beta-IgG+PBL group showed a significant increase as compared with those in the control group and N-IgG+PBL. Pathohistologically, focal infiltration of inflammatory cells in the myocardium was observed in one mouse of the beta-IgG+PBL group. Rabbit CD3-positive T-lymphocytes in the myocardium were observed in two mice of the beta group. In conclusion, transfer of IgG and PBL from rabbits immunized with beta1 peptide was able to induce the early stages of myocardial damage in SCID mice. These data provide direct evidence that the autoimmune mechanism is important in the pathogenesis of dilated cardiomyopathy.
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