Persistence of impaired ventricular function after repair of cyanotic congenital heart defects may be due to previous exposure to chronic hypoxemia or to perioperative ischemic injury. Clarification of this phenomenon was sought in a canine model of cyanotic cardiovascular disease (Group I), in which the left atrium was anastomosed proximal to the banded pulmonary artery. Animals that had pulmonary artery banding alone (Group II) or no prior surgical intervention (Group III) served as controls. All Group I animals became cyanotic during the study period (arterial oxygen tension, 38 +/- 4 mm Hg; hematocrit, 55 +/- 5%). Radionuclide-determined ejection fractions performed three months after operation showed significant depression of global biventricular function by 16 to 29% (p less than 0.05) compared with groups II and III. On cardiopulmonary bypass, all hearts were subjected to 4 degrees C potassium cardioplegic arrest and reperfusion with serial assays for myocardial adenosine triphosphate (ATP) and creatine phosphate (CP) levels. The ATP and CP stores in each ventricle were similar at all sampling intervals, and preischemic levels were comparable in cyanotic and control groups. However, ATP levels were significantly depressed 37 to 43% from preischemic levels (p less than 0.02) after arrest and reperfusion in cyanotic dogs, but they were preserved in Groups II and III. During ischemia, CP stores were depleted to 27% of preischemic values in Group I but only to 46 to 63% of preischemic levels in the control groups (p less than 0.05). These data indicate that chronic hypoxemia impairs global ventricular function and predisposes to the accelerated depletion of high-energy phosphates during cardioplegic arrest.(ABSTRACT TRUNCATED AT 250 WORDS)