MYOCARDIAL MITOCHONDRIAL CALCIUM ACCUMULATION MODULATES NUCLEAR CALCIUM ACCUMULATION AND DNA FRAGMENTATION

Background. Previously, we have shown that normothermic global ischemia increases cytosolic calcium accumulation in both the mature and aged heart. Increased nuclear and mitochondrial calcium accumulation was shown to occur in the aged but not the mature heart, and these age-related differences were associated with increased DNA fragmentation and decreased cellular viability only in the aged heart. Methods. To investigate the relationship between increased mitochondrial and nuclear calcium and DNA fragmentation, mature and aged rabbit hearts were subjected to normothermic global isehemia with and without the addition of ruthenium red to block mitochondrial calcium influx. Cytosolic calcium accumulation was measured in a parallel experiment using fura-2. Results. Ruthenium red ameliorated mitochondrial calcium accumulation and was associated with both decreased DNA fragmentation and decreased nuclear 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.