Circulation, Vol 81, 959-969, Copyright © 1990 by American Heart Association
K Schulze, BF Becker, R Schauer and HP Schultheiss
The adenosine diphosphate (ADP)-adenosine triphosphate (ATP) carrier of the
inner mitochondrial membrane is identified as an autoantigen in myocarditis
and dilated cardiomyopathy. Sera of patients with these diseases contain
autoantibodies to the ADP-ATP carrier capable of inhibiting nucleotide
transport in vitro. Recently, an antibody-related infringement of energy
metabolism was shown in intact perfused hearts isolated from guinea pigs
immunized with the ADP-ATP carrier. A decreased cytosolic-mitochondrial
difference of the phosphorylation potential of ATP was measured that
originated from a reduction in mitochondrial-cytosolic nucleotide
transport. Nonimmunized animals did not show these changes in energy
metabolism, despite being in a comparable metabolic state and performing
equal external heart work. To establish whether antibodies to the ADP-ATP
carrier can also alter cardiac function, hemodynamic parameters of isolated
hearts of guinea pigs that were preimmunized with the carrier protein were
measured. Cardiac metabolism was stimulated by exposing the hearts to a
high calcium concentration in conjunction with a maximum elevation of the
afterload. Mean aortic pressure, stroke volume, stroke work, and external
heart work were found to be lowered significantly (p less than 0.005). The
external heart work of the immunized hearts reached only about 20% of the
level performed by control hearts. Myocardial oxygen consumption was
lowered 2.5-fold, whereas the extent of lactate production was found to be
more than doubled. These results show a diminished cardiac performance of
hearts from animals immunized with the ADP-ATP carrier. Our findings
demonstrate that autoimmunity to the ADP-ATP carrier may contribute to the
pathophysiology of dilated cardiomyopathy as a subsequent stage of
myocarditis by causing an autoantibody-mediated reduction in cardiac
function on the basis of an imbalance between energy delivery and demand.
ARTICLES
Antibodies to ADP-ATP carrier--an autoantigen in myocarditis and dilated cardiomyopathy--impair cardiac function
Department of Internal Medicine, University of Munich, FRG.
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