Disturbance of the myocardial energy metabolism in dilated cardiomyopathy due to autoimmunological mechanisms.

BACKGROUND

After the identification and immunochemical characterization of the ADP/ATP carrier of the inner mitochondrial membrane as an organ- and a conformation-specific autoantigen in myocarditis and dilated cardiomyopathy, we investigated whether an immunoreaction against the ADP/ATP carrier leads to a disturbance of cellular energy metabolism and consequently of myocardial function.

METHODS AND RESULTS

Either immunization of guinea pigs with the isolated carrier protein or infection of A/J mice with coxsackievirus B3 induced heart reactive antibodies against the ADP/ATP carrier and led to a disturbance of the cellular energy metabolism: delta Gcyt-mit: 4.9 +/- 0.6 kJ/mol ATP (controls) to 2.3 +/- 1.1 kJ/mol ATP (immunized animals). In the isolated, perfused working heart preparation, the hemodynamic results of these hearts showed a > 50% reduction in external heart work. Because the amount of the decrease of external heart work and the magnitude of the reduction of delta Gcyt-mit showed a very close correlation, it must be suspected that the imbalance of the myocardial energy metabolism is responsible for the impairment of cardiac function.

CONCLUSIONS

These data suggest that virus infection of the myocardium as shown for viral myocarditis and dilated cardiomyopathy may lead to a disturbed function of the ADP/ATP carrier and, thus, may be the cause of impaired myocardial function.