MAGNESIUM CARDIOPLEGIA ENHANCES MESSENGER-RNA LEVELS AND THE MAXIMAL VELOCITY OF CYTOCHROME-OXIDASE-I IN THE SENESCENT MYOCARDIUM DURING GLOBAL-ISCHEMIA

Background The aged myocardium accumulates significantly more cytosoli c calcium [Ca2+](i) during ischemia, and functional recovery is more s everely compromised as compared with the mature heart. Cardioplegia am eliorates these phenomena. The mechanism by which increased calcium ac cumulation reduces functional recovery in the senescent myocardium is unknown, but it has been suggested that futile calcium cycling in the mitochondria leading to depletion of ATP stores during normothermic gl obal ischemia may be involved. Methods and Results To investigate the effect of cardioplegia on mitochondrial calcium ([Ca2+](mt)) accumulat ion and the expression of cytochrome oxidase I (COX I) during global i schemia, mitochondria were isolated from mature (age, 15 to 20 weeks) and aged (age >130 weeks) rabbit hearts after Langendorff perfusion. F ive perfused heart groups were investigated: 30 minutes of global isch emia without treatment (control), with potassium (K, 20 mmol/L), magne sium (Mg, 20 mmol/L), or potassium and magnesium (K/Mg) cardioplegia. No significant difference in [Ca2+](mt) was evident in mature hearts w ith any protocol. In aged hearts, [Ca2+](mt) was increased in global i schemia but was ameliorated with Mg and K/Mg cardioplegia. COX I mRNA levels in aged hearts were lower in both control and global ischemia b ut were increased with cardioplegia. Maximal velocities for COX I were significantly increased with Mg cardioplegia both in the mature and t he aged myocardium. Conclusions K and/or Mg cardioplegia ameliorates [ Ca2+](mt) accumulation in aged hearts during normothermic global ische mia and increases COX I mRNA levels to a level not significantly diffe rent from that found in mature hearts.