We examined the effects of ischemic preconditioning (IP) on metabolic and contractile function during coronary hypoperfusion in dogs. After the left anterior descending coronary artery (LAD) was occluded for 5 min (IP) and reperfused for 10 min, coronary blood flow (CBF) of the LAD was decreased to 33% of the control. IP increased (P < 0.05) lactate extraction ratio and the pH of coronary venous blood and decreased (P < 0.05) myocardial oxygen consumption and fractional shortening during hypoperfusion compared with those in the control group, although IP did not change the endocardial-to-epicardial blood flow ratio of the regional myocardium during hypoperfusion. IP increased (P < 0.05) the adenosine levels in coronary venous blood during hypoperfusion. IP increased (P < 0.05) myocardial ecto-5'-nucleotidase activity. Administration of 8-sulfophenyltheophylline or ,-methyleneadenosine 5'-diphosphate blunted the IP-induced changes in metabolic and contractile parameters during hypoperfusion. These results suggest that IP reduced the severity of anaerobic myocardial metabolism of ischemic hearts by increasing the adenosine levels via an extracellular pathway.