The cardioprotective effect of the magnesium and calcium content of hyperkalemic cardioplegic solutions was investigated using isolated rat hearts subjected to hypothermic ischemic arrest. Hearts were arrested for 180 minutes at 20 degrees C by administering a 3-minute infusion of cardioplegic solution containing various concentrations of magnesium and calcium. Treatment groups received solution with either 0, 8, or 16 mmol/L magnesium. For each of these magnesium concentrations, 0.1, 0.6, or 1.2 mmol/L calcium was also present in the solution. At each concentration of magnesium, the percentage recovery of aortic flow was dependent on the calcium concentration. The maximum percentage recovery of aortic flow was 67.9% +/- 2.3% (mean +/- standard error of the mean) in the Mg-free, 0.1 mmol/L Ca group, whereas it was 65.1% +/- 2.7% in the 8 mmol/L Mg, 0.1 mmol/L Ca group and 70.0% +/- 3.5% in the 16 mmol/L Mg, 0.6 mmol/L Ca group. No significant differences in the recovery of cardiac function and creatine kinase leakage were observed between the three groups. The findings suggested that the cardioprotective effect was dependent on the relative concentration of both magnesium and calcium, and that it is important to maintain an appropriate ionic balance in cardioplegic solutions.