Low cardiac output after surgically induced myocardial ischemia is a major contributor to mortality and morbidity after operations for congenital heart defects, despite myocardial "protection" with the techniques of hypothermia and cardioplegia that have been effective in protecting mature myocardium. The purpose of this study was to investigate the effectiveness of topical cooling to 15 degrees C, crystalloid cardioplegia, and blood cardioplegia in protecting 28 isolated neonatal lamb hearts subjected to 2 hours of ischemia. Seven hearts were isolated and perfused in a similar manner with cooling to 15 degrees C but were then rewarmed without any ischemia to serve as a control group. All three groups (topical cooling, crystalloid cardioplegia, and blood cardioplegia) had recovery of systolic function (as measured by maximum developed pressure, maximum rate of pressure rise, peak developed pressure at a fixed volume, and peak rate of pressure rise at a fixed volume) equal to the control group; the exception was peak rate of pressure rise at a fixed volume in the blood cardioplegia group, in which recovery was worse than in the control group. No differences among three ischemia groups or in comparison with the control group were found for measures of diastolic function (ventricular diastolic pressure at a fixed volume or stiffness constant kA). Systolic function declined in all groups (including control) from baseline to the end of the experiment. These findings suggest that hypothermia exerted the dominant protective effect in these normal neonatal lamb hearts and there was no added protection from either crystalloid or blood cardioplegia.