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 mitochondri a (mt) have been observed in the atrial muscles of patients with atrial fib rillation (AF) and of animals with rapid atrial pacing, however, it is not known whether the mitochondrial function is impaired in human atrium with A F. Materials and Methods We determined adenine nucleotides concentrations and mtDNA deletions in 26 human right atria obtained at the time of cardiac sur gery, using HPLC and PCR amplification, and studied the relationship betwee n 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 p atients with a mtDNA deletion of 7.4 kb than in those without a deletion; t here were no significant differences regarding haemodynamic parameters betw een the two groups. The concentrations of ATP, ADP, AMP and total adenine n ucleotides in the right atrium were significantly lower in the patients wit h mtDNA deletions than the patients without a deletion. In a gender- and di seased-matched population, the mtDNA deletion was still significantly assoc iated with age and a decreased concentration of adenine nucleotides in the atrium. Using quantitative PCR analysis, the proportion of mtDNA deletion t o normal mtDNA of the atrium, was estimated to be 0.3-2% in four cases. Conclusion 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 m tDNA deletion were the result or the cause of an impaired ATP synthesis, ag eing, hemodynamic deterioration, or AF.