Opposing cardiac effects of autoantibody activation of beta-adrenergic and M2 muscarinic receptors in cardiac-related diseases

INTERNATIONAL JOURNAL OF CARDIOLOGY

卷:148

Article

Stavrakis, Stavros^1,2  Kem, David C.^1,2,3  Patterson, Eugene^1,2,4  Lozano, Pedro^1,2  Huang, Shijun^1,2,3  Szabo, Bela^1,2  Cunningham, Madeleine W.⁵  Lazzara, Ralph^1,2  Yu, Xichun^1,2,3 

[1] Univ Oklahoma, Hlth Sci Ctr, Cardiol & Heart Rhythm Inst, Oklahoma City, OK USA

[2] VA Med Ctr, Oklahoma City, OK USA

[3] Univ Oklahoma, Hlth Sci Ctr, Endocrinol & Harold Hamm Oklahoma Diabet Ctr, Oklahoma City, OK USA

[4] Univ Oklahoma, Hlth Sci Ctr, Dept Cell Biol, Oklahoma City, OK USA

[5] Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73190 USA

关键词: Cardiomyopathy;    Activating autoantibodies;    beta-adrenergic receptors;    M2 muscarinic receptor;    Inotropy;   

DOI  :  10.1016/j.ijcard.2009.11.025

来源: Elsevier

【 摘 要 】

Background: Activating autoantibodies to beta-adrenergic receptors (AA beta 1/2AR) and M2 muscarinic receptors (AAM2R) have been reported in several cardiac diseases and may have pathophysiologic relevance. However, the interactions and relative effects of AA beta 1AR, AA beta 2AR and AAM2R on contractile function have not been characterized. Methods: The inotropic effects of IgG from 18 selected patients with cardiomyopathy and/or atrial tachyarrhythmias positive by ELISA for antibodies to beta 1/2AR were studied using an isolated canine Purkinje fiber contractility assay. M2R-blockade was tested using atropine while selective beta 1AR and beta 2AR blockade used CGP-20712A and ICI-118551 respectively. Results: Fifteen of the 18 anti-beta 1/2AR ELISA-positive samples demonstrated evidence for negative inotropic muscarinic effects which were blocked using atropine. Atropine failed to uncover a positive inotropic response in 2 of the 18 IgG samples (false positive ELISA for AA beta AR). In the remaining 16 AA beta AR true-positive subjects, the beta 1AR-induced increase in contractility (concurrent M2/beta 2 blockade) was augmented to 140.5+/-12.2% of baseline compared to 127.4+/-7.2% of baseline with M2 blockade (atropine) only (p<0.001, n=16). The beta 2AR-induced increase in contractility (concurrent M2/beta 1 blockade) was only 114.5+/-4.3% of baseline (p<0.001, n=16). Combined M2 and beta 1/beta 2 blockade eliminated any increase in contractility. Conclusions: The inherently positive inotropic effect of AA beta 1AR was negatively modulated by AAM2R and AA beta 2AR. These opposing effects of receptor-activating autoantibodies may alter cardiac performance and influence clinical outcome depending on their receptor type and relative contractile activity. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

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