© 1995 American Heart Association, Inc.
Articles |
Antibody-Mediated Imbalance of Myocardial Energy Metabolism
A Causal Factor of Cardiac Failure?
From Medizinische Klinik B, Heinrich-Heine Universität, Düsseldorf, Germany.
Correspondence to Karsten Schulze, MD, Medizinische Klinik B, Heinrich-Heine Universität, Moorenstr 5, 40225 Düsseldorf, Germany.
Abstract The ADP-ATP carrier of the inner mitochondrial
membrane is an autoantigen in myocarditis and dilated cardiomyopathy.
Sera of patients with these diseases contain carrier-specific
autoantibodies that inhibit the transmembrane nucleotide transport on
isolated mitochondria. Guinea pigs immunized with the isolated ADP-ATP
carrier protein also generate specific carrier-inactivating antibodies.
In this study, we measured the cardiac function of guinea pigs
immunized with the ADP-ATP carrier by determining the external heart
work (EHW) of their isolated perfused spontaneously beating hearts
stimulated by 4.0 mmol/L calcium and aortic ligature. Further, the
electrogenic transport activity of the ADP-ATP carrier was estimated by
calculating the cytosolic-mitochondrial difference of the
phosphorylation potential of ATP [
G(cyt-mit)] in the
freeze-clamped isolated hearts by nonaqueous fractionation. The EHW of
immunized guinea pigs was seen to be reduced by 54%
(P<.005) compared with nonimmunized control guinea pigs,
and G(cyt-mit) declined from 4.9 kJ/mol ATP in nonimmunized
control hearts to 2.3 kJ/mol ATP in the hearts of the immunized guinea
pigs (P<.005). The decisive result of this study, however,
is the close relation observed between the magnitude of reduction of
G(cyt-mit) and the size of the decrease in EHW (r=.87).
Therefore, it seems plausible that antibody-mediated carrier
dysfunction (creating the observed imbalance in myocardial energy
metabolism) is responsible for the impairment of cardiac function. Our
data support the hypothesis that immunopathic mechanisms in myocarditis
and dilated cardiomyopathy can trigger subsequent heart failure. The
underlying pathophysiological reason seems to be a metabolic disorder
initiated by the antibody-mediated inactivation of the ADP-ATP carrier.
Key Words: • ADP-ATP carrier • phosphorylation potential • myocarditis • cardiomyopathy
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