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Updated: Jul 30, 2026
Transthoracic Echocardiographic Examination in the Rabbit Model
Published on: June 1, 2019
Prevention of experimental autoimmune cardiomyopathy in rabbits by receptor blockers
1Department of Cardiology, Kanazawa Medical University, Uchinada, Ishikawa, Japan. matsui@kanazawa-med.ac.jp
Abstract:
We investigated the effects of beta1-adrenoceptor blockade and M2-muscarinic receptor antagonist in rabbits which have developed dilated cardiomyopathy-like changes after immunization with the peptides from the second extracellular loop of human beta1-adrenoceptor (beta1-peptide) and M2-muscarinic receptor (M2-peptide). Ten rabbits, which were immunized with beta1-peptide once a month for one year, were treated with bisoprolol and 10 rabbits, which were immunized with M2-peptide, were treated with otenzepad. Although both groups treated with receptor blockade or antagonist showed an increased titer of anti-beta1-adrenoceptor or anti-M2-muscarinic receptor antibodies, myocardial damages were markedly less than those in beta1-peptide- or M2-peptide-immunized rabbits. This study indicates that anti-beta1-adrenoceptor and anti-M2-muscarinic receptor antibodies are of pathogenic importance in the development of human dilated cardiomyopathy, and that beta-adrenoceptor blockade, bisoprolol, and M2-muscarinic receptor antagonist, otenzepad, might be clinically useful for treatment of dilated cardiomyopathy.
Insights
Beta-blockers like bisoprolol and M2-muscarinic receptor antagonists like otenzepad may treat dilated cardiomyopathy. These drugs reduced heart damage in rabbits immunized with specific peptides, suggesting antibody involvement in the disease.
Area of Science:
- Cardiology
- Immunology
- Pharmacology
Background:
- Dilated cardiomyopathy (DCM) can be experimentally induced by immunization with peptides from adrenoceptors.
- Autoantibodies against beta1-adrenoceptors and M2-muscarinic receptors are implicated in DCM pathogenesis.
Purpose of the Study:
- To investigate the therapeutic potential of beta1-adrenoceptor blockade and M2-muscarinic receptor antagonism in a rabbit model of DCM.
- To assess the role of specific autoantibodies in the development of heart damage.
Main Methods:
- Rabbits were immunized with beta1-peptide or M2-peptide to induce DCM-like changes.
- Treated groups received either bisoprolol (beta1-blocker) or otenzepad (M2-antagonist).
- Antibody titers and myocardial damage were evaluated.
Main Results:
- Both bisoprolol and otenzepad treatments increased autoantibody titers against beta1-adrenoceptors and M2-muscarinic receptors, respectively.
- Myocardial damage was significantly reduced in rabbits treated with bisoprolol or otenzepad compared to untreated controls.
- This suggests a protective effect of receptor blockade/antagonism despite increased antibody levels.
Conclusions:
- Autoantibodies against beta1-adrenoceptors and M2-muscarinic receptors play a pathogenic role in DCM.
- Beta-adrenoceptor blockade (bisoprolol) and M2-muscarinic receptor antagonism (otenzepad) show potential as clinical treatments for dilated cardiomyopathy.
