Reperfusional damage refers to the serious structural, functional, and metabolic derangements commonly observed during restoration of coronary circulation following cardiopulmonary bypass. Damage is believed to result from ischemic injury incurred during aortic cross-clamping and unmasked in the recovery period and/or certain metabolic processes activated during postischemic reperfusion. It has been postulated that reperfusional damage can be minimized or eliminated if normal myocardial metabolic parameters can be maintained or restored before the initiation of reperfusion. Studies have tested a variety of cardioplegic solution compositions and administration modes. However, much controversy exists over the different methods. We have tested the hypothesis that improved myocardial protection during cardioplegia can prevent reperfusional damage and investigated the possibility of achieving optimal myocardial protection. Elective cardiac arrest was induced in isolated perfused rat hearts, under working conditions reported previously. We tested two arresting temperatures (8 degrees C and 28 degrees C), three infusion frequencies (single, double, and multiple dose), and different combinations of cardioplegic additives with demonstrated benefits (glucose, adenosine, creatine, and albumin). Metabolic and hemodynamic functions were used to evaluate the protection of the ischemic myocardium. Glucose (0.5%) and adenosine (1 mmol/L) provided clear benefits under all experimental conditions. Double-dose cardioplegia at 8 degrees C also surpassed the single- and multiple-dose groups. When oxygenated cardioplegic solution containing glucose and adenosine was reinfused for 1 minute after 30 minutes of cross-clamping, no measurable changes were detected after ischemic arrest, as compared with normal hearts. Reperfusional damage was eliminated by this procedure. We concluded that an optimal condition for myocardial preservation during elective cardiac arrest in our model was established.