MYOCARDIAL MITOCHONDRIAL CALCIUM ACCUMULATION MODULATES NUCLEAR CALCIUM ACCUMULATION AND DNA FRAGMENTATION

Background. Previously, we have shown that normothermic global ischemi a increases cytosolic calcium accumulation in both the mature and aged heart. Increased nuclear and mitochondrial calcium accumulation was s hown to occur in the aged but not the mature heart, and these age-rela ted differences were associated with increased DNA fragmentation and d ecreased cellular viability only in the aged heart. Methods. To invest igate the relationship between increased mitochondrial and nuclear cal cium and DNA fragmentation, mature and aged rabbit hearts were subject ed to normothermic global isehemia with and without the addition of ru thenium red to block mitochondrial calcium influx. Cytosolic calcium a ccumulation was measured in a parallel experiment using fura-2. Result s. Ruthenium red ameliorated mitochondrial calcium accumulation and wa s associated with both decreased DNA fragmentation and decreased nucle ar calcium accumulation. Conclusions. Nuclear calcium accumulation was correlated with increased mitochondrial calcium accumulation but not increased cytosolic calcium accumulation in the aged heart. Modulation of mitochondrion ''futile calcium cycling'' may be of significance in the modulation of ischemic myocardial injury.