October 1, 1999Open Access
View Full PaperDisturbance of myocardial energy metabolism in experimental virus myocarditis by antibodies against the adenine nucleotide translocator
Key Result
Coxsackie B3 virus infection in mice significantly reduced the cytosolic ATP/ADP ratio compared to noninfected controls (59 vs 136; P<0.05), indicating altered cardiac energy metabolism.
Structured PICO
P
Population
19 A.SW/SnJ-mice with experimental virus myocarditis induced by Coxsackie B3 virus infection, compared to noninfected controls.
E
Exposure
Coxsackie B3 virus infection
C
Comparator
Noninfected control mice
O
Outcome
Cytosolic and mitochondrial ATP/ADP-ratios, and cardiac function parameters (left ventricular pressure, rate-pressure product, dp/dt, oxygen consumption) in isolated perfused heartssurrogate
Experimental Coxsackie B3 virus myocarditis alters cardiac energy metabolism and function, likely via antibody-mediated modulation of the adenine nucleotide translocator.
Main Result
Absolute Event Rate: 59% vs 136%
p-value: p=<0.05
Abstract
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. METHODS AND 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. CONCLUSION: 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.