Ischemic preconditioning has not been investigated in a clinically relevant model of hypothermic multidose cardioplegia arrest. Using isolated rabbit hearts perfused on a Langendorff apparatus, ischemic preconditioning was investigated as an adjunct to crystalloid cardioplegia during a 2.5-hour ischemic period at 15 degrees C. After baseline functional data were obtained, ischemic preconditioning was induced with either 1 minute or 5 minutes of normothermic ischemia, followed by 5 minutes of reperfusion before the arrest period. Control hearts underwent no ischemic preconditioning. The control hearts exhibited a decrement in both the peak developed pressure and diastolic function, as measured by the slope of the diastolic pressure-volume relationship, of from 107 +/- 2 to 68 +/- 7 mm Hg (p < 0.005) and from 0.99 +/- 0.2 to 2.95 +/- 0.44 mm Hg/0.1 mL (p < 0.005), respectively. Hearts exposed to either 1 or 5 minutes of normothermic ischemia showed no significant change in the slope of the diastolic pressure-volume relationship. Hearts exposed to 1 or 5 minutes of normothermic ischemia also had a significant decrease in the peak developed pressure of from 107 +/- 6 to 92 +/- 2 mm Hg and from 102 +/- 3 to 85 +/- 4 mm Hg, respectively (p < 0.05). However, ischemic preconditioning brought about a significant improvement in the postischemic peak developed pressure, as opposed to that seen for the control hearts (p < 0.05). Creatine kinase washout was significantly higher in the control hearts only. High-energy phosphate levels, lactate levels, the percentage wet weight, and tissue creatine phosphate levels were not significantly different among the groups.(ABSTRACT TRUNCATED AT 250 WORDS)