Myocardial preservation for prolonged ischemia has traditionally centered around deep hypothermia with metabolic arrest. This approach is limited in tolerable ischemic time by the state of energy reserves at the onset of ischemia, because anaerobic glycolysis during ischemia is limited by end-product accumulation (lactate, alanine, and H+). In this study we evaluated a novel preservation solution containing the basic amino acid histidine to buffer H+, glucose as substrate, and low sodium and calcium concentrations to mimic the intracellular ionic environment. Isolated rabbit hearts were subjected to hypothermic ischemia for 8 and 16 hours at 4 degrees and 21 degrees C followed by reperfusion. The buffered solution was compared to University of Wisconsin solution (high potassium). Intracellular pH was maintained at preischemic levels in the buffered solution hearts at 21 degrees C, and this was associated with better preservation of high energy stores and recovery of contractile function. Developed pressure recovered to 90% +/- 3% of preischemic values after 16 hours of 21 degrees C ischemia with the buffered solution as compared with 79% +/- 2% in the University of Wisconsin group at 4 degrees C (contracture occurred in the University of Wisconsin hearts at 21 degrees C). The optimal temperature in the buffered solution hearts was 13 degrees C, and with this temperature acceptable recovery of contractile function was seen after 24 hours of ischemia. On the basis of these results, we conclude that promoting anaerobic glycolysis during ischemia achieves superior prolonged preservation of energetic and contractile function of the heart.