Previous studies suggest glucose, insulin and potassium (GIK) infusion during ischemia reduces infarct size and improves post-ischemic myocardial function in acute myocardial infarction and following surgical revascularization of the heart. The potential use of GIK when given only during reperfusion after a period of global ischemia, as might occur during cardiac arrest, is unclear. To test the hypothesis that GIK reperfusion improves post-ischemic myocardial bioenergetics and function, we utilized a perfused heart model. Hearts from Sprague-Dawley rats (350-450 g) were perfused at 85 mmHg with oxygenated Krebs-Henseleit bicarbonate containing 5.5 mM glucose and 0.2 mM octanoic acid. Following 20 min of global ischemia, hearts were reperfused for 30 min with original solution (control) or GIK in two different doses (10 or 20 mM glucose each with insulin 10 U/l and K(+) 7 meq/l). Hearts perfused with GIK solutions had significantly higher ATP, creatine phosphate, energy charge, and NADP(+) and lower AMP and inosine levels compared with control after 30 min of reperfusion. Hearts reperfused with GIK had significantly higher developed pressure and higher dP/dt than control reperfused hearts. Reperfusion with GIK improved post-ischemic recovery of both contractile function and the myocardial bioenergetic state. GIK may be a viable adjunctive reperfusion therapy following the global ischemia of cardiac arrest to improve post-resuscitation cardiac dysfunction.