Faculty Collaboration Database

Opposing cardiac effects of autoantibody activation of β-adrenergic and M2 muscarinic receptors in cardiac-related diseases. Int J Cardiol 2011 May 05;148(3):331-6

Date

01/08/2010

Pubmed ID

20053466

Pubmed Central ID

PMC3108570

DOI

10.1016/j.ijcard.2009.11.025

Scopus ID

2-s2.0-79955044718 (requires institutional sign-in at Scopus site)   39 Citations

Abstract

BACKGROUND: Activating autoantibodies to β-adrenergic receptors (AAβ1/2AR) and M2 muscarinic receptors (AAM2R) have been reported in several cardiac diseases and may have pathophysiologic relevance. However, the interactions and relative effects of AAβ1AR, AAβ2AR 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 β1/2AR were studied using an isolated canine Purkinje fiber contractility assay. M2R-blockade was tested using atropine while selective β1AR and β2AR blockade used CGP-20712A and ICI-118551 respectively.

RESULTS: Fifteen of the 18 anti-β1/2AR 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 AAβAR). In the remaining 16 AAβAR true-positive subjects, the β1AR-induced increase in contractility (concurrent M2/β2 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 β2AR-induced increase in contractility (concurrent M2/β1 blockade) was only 114.5±4.3% of baseline (p<0.001, n=16). Combined M2 and β1/β2 blockade eliminated any increase in contractility.

CONCLUSIONS: The inherently positive inotropic effect of AAβ1AR was negatively modulated by AAM2R and AAβ2AR. These opposing effects of receptor-activating autoantibodies may alter cardiac performance and influence clinical outcome depending on their receptor type and relative contractile activity.

Author List

Stavrakis S, Kem DC, Patterson E, Lozano P, Huang S, Szabo B, Cunningham MW, Lazzara R, Yu X

Author

Pedro Lozano MD Associate Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adrenergic beta-Agonists
Adrenergic beta-Antagonists
Adult
Aged
Animals
Autoantibodies
Dogs
Female
Heart Diseases
Humans
Male
Middle Aged
Purkinje Fibers
Receptor, Muscarinic M2
Receptors, Adrenergic, beta
Receptors, Adrenergic, beta-1
Receptors, Adrenergic, beta-2