BACKGROUND We previously evaluated cardioprotective effects of glucose-insulin-potassium (GIK) in a porcine ischemia-reperfusion model; our results showed less myocardial pH decrease during ischemia and reperfusion and faster normalization of ATP and glucose during reperfusion. The proposed protective mechanism was facilitation of glucose transport for myocardial metabolism. The objective of this study was to assess the impact of insulin-potassium (IK) alone on myocardial metabolism. METHODS Male swine received continuous infusion of IK (IK group, n = 10), GIK (GIK group, n = 10), or standard lactated Ringer's (LR) solution (controls, n = 10). Induction of 20 minutes of ischemia in the left anterior descending (LAD) artery distribution was followed by 20 minutes of reperfusion. Real-time biosensors recorded pH and glucose levels in ischemic and nonischemic beds. Myocardial biopsies in the distribution of the LAD assessed ATP levels. Groups were compared using the Kruskal-Wallis and Mann-Whitney tests. RESULTS Real-time data are presented as percent change from baseline. At less than 10 minutes of ischemia, the average pH change was less for the IK group than the LR group (0.03% +/- 0.21% vs -2.06% +/- 1.23%; P = .001), and the pH change in the IK group was similar to the GIK group. After 10 minutes of ischemia and during the first 10 minutes of reperfusion, the IK group experienced pH changes that were similar to the LR group. Biopsies after 20 minutes of ischemia and 20 minutes of reperfusion showed less of a decline in ATP levels for the IK group compared to the LR group. Glucose at all time points demonstrated no statistically significant differences. CONCLUSIONS IK infusion alone demonstrates cardioprotective effects during early ischemia; however, compared to GIK infusion after 20 minutes of ischemia and reperfusion, myocardial pH and glucose levels were not sustained. Although insulin may facilitate glucose transport during ischemia, additional glucose in combination with IK enhances myocardial protection during reperfusion. This finding suggests that GIK enhancement during acute ischemia-reperfusion may improve myocardial protection.