This study examines the efficacy of three methods for myocardial protection during 8 hours of global ischema at 10 degrees C in immature (28 days) rat hearts subjected to lifelong hypoxia afforded by exposure to simulated high altitude. Hearts in group 1 were protected by rapid topical cooling alone, in group 2 by slow pre-arrest cooling with Krebs-Henseleit solution plus topical cooling and in group 3 by coronary perfusion with St. Thomas' Hospital cardioplegia No 2 (STS 2) plus topical cooling. Hearts in groups 4-6 served as controls without hypoxia and were protected accordingly. Parameters of myocardial function (left ventricular pressure, LVP), the metabolic status (myocardial concentration of ATP and creatine phosphate) and endothelial function (response to the vasodilator acetylcholine) were measured. Myocardial protection by rapid topical cooling alone resulted in equal--or significantly improved--postischemic recovery of LVP and endothelial function compared with slow pre-arrest cooling or additional protection with STS 2. The data advocate topical cooling for myocardial protection during surgical correction of cyanotic congenital cardiac disease in early infancy. In this age group, coronary perfusion with cold crystalloid solutions appears to aggravate ischemic endothelial injury.