The purpose of this study was to clarify the metabolic events that explain why supplemental glucose is detrimental during cardiac storage. Four solutions were used to flush and store porcine hearts: St. Thomas Hospital Solution (STHS), University of Wisconsin (UW) solution, and UW + 90 mM histidine, and UW + 90 mM histidine + 11 mM glucose. Despite equivalent increases in lactate in the two histidine-buffered groups throughout 10 h of storage, glycogen utilization was evident in the group without supplemental glucose. The presence of glucose resulted in a reduction in energy production, presumably mediated by direct inhibition of glycogenolysis. Furthermore, UW + histidine was the only group to show consistent improvements in ATP and total adenylates. It was concluded that inclusion of the buffering agent, histidine, to UW solution promotes anaerobic energy production as a result, in part, of preserved high levels of the regulatory control enzyme, phosphofructokinase.