Is age a contributory factor of mitochondrial bioenergetic decline and DNAdefects in idiopathic dilated cardiomyopathy?

While mitochondrial abnormalities are increasingly recognized in cardiac di seases including hypertrophic cardiomyopathy, their presence in idiopathic dilated cardiomyopathy and the role th;lt ape plays in their incidence and severity have yet not bern assessed. Levels of cardiac respiratory enzyme a ctivities and mitochondrial DNA (mtDNA) were examined in 55 subject with id iopathic dilated cardiomyopathy divided into 3 age groups. Respiratory enzy me activity levels were significantly lower in 37 patients (67%) compared t o age-matched controls and increased activity levels were noted in 9 (16%). Decreased activities were found in complex I (n = 11), III (n = 16), IV (n = 12) and V (n = 13), but not in II, the only respiratory complex entirely nuclear-encoded, No age-specific differences were found in the overall fre quency of enzymatic abnormalities. However, older patients had significantl y increased multiple enzyme activity defects as well as increases in abunda nce and frequency of the 7.4 kb deletion, In addition, 3 patients were note d with marked reduction in mtDNA levels. None of the pathogenic mtDNA mutat ions previously associated with hypertrophic cardiomyopathy were found, nor was there any relationship that could be established between levels of spe cific mtDNA deletions and enzyme activities. In summary, specific mitochond rial abnormalities are heterogenous and frequent in both adults and childre n with idiopathic dilated cardiomyopathy. Older patients are more likely to have mtDNA deletions and multiple enzyme activity defects. The molecular b asis for these abnormalities remains undefined. (C) 1999 by Elsevier Scienc e Inc.