Mitochondrial DNA deletion associated with the reduction of adenine nucleotides in human atrium and atrial fibrillation.
BACKGROUND
Structural changes in the number, size, and shape of mitochondria (mt) have been observed in the atrial muscles of patients with atrial fibrillation (AF) and of animals with rapid atrial pacing, however, it is not known whether the mitochondrial function is impaired in human atrium with AF.


METHODS
We determined adenine nucleotides concentrations and mtDNA deletions in 26 human right atria obtained at the time of cardiac surgery, using HPLC and PCR amplification, and studied the relationship between mtDNA deletions and clinical manifestations, the haemodynamic parameters of the patients and adenine nucleotide concentrations in their atrium.


RESULTS
The age and the prevalence of AF were significantly higher in the patients with a mtDNA deletion of 7.4 kb than in those without a deletion; there were no significant differences regarding haemodynamic parameters between the two groups. The concentrations of ATP, ADP, AMP and total adenine nucleotides in the right atrium were significantly lower in the patients with mtDNA deletions than the patients without a deletion. In a gender- and diseased-matched population, the mtDNA deletion was still significantly associated with age and a decreased concentration of adenine nucleotides in the atrium. Using quantitative PCR analysis, the proportion of mtDNA deletion to normal mtDNA of the atrium, was estimated to be 0.3-2% in four cases.


CONCLUSIONS
These results suggest that the deletion of mtDNA associated with ageing or AF can lead to a bioenergetic deficiency due to an impaired ATP synthesis in the human atrium; however, no conclusion can be made whether mtDNA deletion were the result or the cause of an impaired ATP synthesis, ageing, hemodynamic deterioration, or AF.
Tsuboi
M
M
Department of Medicine, Tottori University, Yonago, Japan.
Hisatome
I
I
Morisaki
T
T
Tanaka
M
M
Tomikura
Y
Y
Takeda
S
S
Shimoyama
M
M
Ohtahara
A
A
Ogino
K
K
Igawa
O
O
Shigemasa
C
C
Ohgi
S
S
Nanba
E
E
D000227:Adenine Nucleotides / Q000235:genetics* / Q000378:metabolism*; D000328:Adult; D000368:Aged; D001281:Atrial Fibrillation / Q000235:genetics* / Q000378:metabolism; D002648:Child; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006325:Heart Atria / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008929:Mitochondria, Heart / Q000235:genetics* / Q000378:metabolism; D010084:Oxidation-Reduction; D017384:Sequence Deletion / Q000235:genetics*
D000227:Adenine Nucleotides; D004272:DNA, Mitochondrial