Enhanced external counterpulsation (EECP) is noninvasive, safe, and effective for stable angina. We have reported that the development of functional collateral vessels is one of the mechanisms of EECP therapy using ammonia positron emission tomography (PET). The efficacy of heparin treatment on collateral growth is shown in several clinical studies. We evaluated whether EECP combined with intravenous heparin injection is effective for exercise capacity and oxygen metabolism of ischemic myocardium in stable angina. Eleven patients with stable angina were treated with conventional EECP therapy (C group). Seven patients with stable angina were treated with EECP therapy with 5000 IU heparin pretreatment (H group). At baseline and after the completion of treatment H, 7 patients underwent [(11)C] acetate PET to examine the change in regional myocardial oxygen metabolism. Although the total treadmill exercise time was prolonged after treatment in both groups, the extent of the improvements was significantly greater in the H group compared with the C group. Although k mono, the index of regional myocardial oxygen metabolism, in the nonischemic region remained unchanged, k mono in the ischemic region increased significantly ( P << 0.05) from 0.038 +/- 0.004 to 0.053 +/- 0.007. In conclusion, EECP with heparin pretreatment appears to be a new treatment remedy for patients with stable angina.