Disturbance of myocardial energy metabolism in experimental virus myocarditis by antibodies against the adenine nucleotide translocator.
OBJECTIVE
The adenine nucleotide translocator (ANT) of the inner mitochondrial membrane is an autoantigen in myocarditis and in dilated cardiomyopathy. Clinical and experimental studies showed that specific autoantibodies inhibit the transmembrane nucleotide transport. In isolated hearts of guinea pigs immunized with the ANT, energy metabolism is disturbed. This metabolic disorder is related to functionally active specific antibodies and to a reduced heart function. This study tests whether similar immunological, metabolical and functional responses also occur in experimental virus myocarditis.


RESULTS
Experimental virus myocarditis was induced in A.SW/SnJ-mice by Coxsackie B3 virus infection. Specific antibodies against the ANT were detected by Western Blot in 14 out of 19 infected animals. In the isolated perfused hearts of five of these 14 mice cytosolic and mitochondrial ATP/ADP-ratios, determined by nonaqueous fractionation, were significantly altered, signalling a reduced ANT function [cytosolic ATP/ADP: 59 +/- 18 vs. 136 +/- 20 (controls), mitochondrial ATP/ADP: 4.2 +/- 1.0 vs. 1.1 +/- 0.3], all P < 0.05. Also, left ventricular pressure [43 +/- 9 vs. 78 +/- 6 mmHg (noninfected controls)], rate-pressure product (15.8 +/- 3.2 vs. 30.5 +/- 3.0 mmHg/min/1000), dp/dt (2410 +/- 222 vs. 3250 +/- 118 mmHg/s), and oxygen consumption (4.7 +/- 0.9 vs. 7.3 +/- 0.7 mumol/g/min), all P < 0.05, were lowered.


CONCLUSIONS
The data support the hypothesis that a virus infection alters cardiac energy metabolism and function by an antibody-mediated modulation of the function of the ANT.
Schulze
K
K
Department of Cardiology, Benjamin Franklin Hospital, Free University of Berlin, Germany.
Witzenbichler
B
B
Christmann
C
C
Schultheiss
H P
HP
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001323:Autoantibodies / Q000032:analysis / Q000378:metabolism*; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D003600:Cytosol / Q000378:metabolism; D004734:Energy Metabolism; D029822:Enterovirus B, Human / Q000276:immunology*; D005260:Female; D051379:Mice; D008815:Mice, Inbred Strains; D008929:Mitochondria, Heart / Q000378:metabolism; D000226:Mitochondrial ADP, ATP Translocases / Q000276:immunology*; D009205:Myocarditis / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D009206:Myocardium / Q000276:immunology / Q000378:metabolism*; D010477:Perfusion; D017725:Ventricular Pressure
D001323:Autoantibodies; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000226:Mitochondrial ADP, ATP Translocases