Long-term amiodarone administration protects against global myocardial ischemia. Reports on the effects of amiodarone on cardiac function have been variable. This study addresses the effect of long-term amiodarone administration on recovery of cardiac function after a period of global ischemia. Normotensive and spontaneously hypertensive rats were used. Normotensive rats (n = 6) received 240 mg/kg amiodarone for 4 weeks, for a total of 72 +/- 3 mg. Hypertensive rats (n = 6) received 500 mg/kg amiodarone for 4 weeks, for a total of 116 +/- 5 mg. Final myocardial concentrations of amiodarone and desethylamiodarone were 1.85 +/- 1.75 and 0.50 +/- 0.61 micrograms/g wet weight for the normotensive rats and 1.30 +/- 0.58 and 0.31 +/- 0.17 micrograms/g for the hypertensive rats (p = nonsignificant). Equal numbers of controls received sterile saline solution for 4 weeks. The hearts were excised and perfused in a Langendorff apparatus. The results indicate that, after 15 minutes of normothermic ischemia, hearts treated with this relatively low dose of amiodarone recovered a greater percentage of preischemic work (97% +/- 13%) as compared with the controls (76% +/- 17%) (p less than 0.005). 