Alternative strategies to optimize preexisting cardioplegia during myocardial preservation are currently under extensive investigation. Adenosine, an endogenous purine nucleoside, has been approved for its cardioprotective potential against ischemic-reperfusion injury. Yet, little information is available with respect to the use of adenosine for cardioplegic induction in humans. The purpose of the present study was, therefore, to assess the clinical relevance of intra-aortic administration of adenosine following aortic cross-clamping with respect to the exertion of additional protection in routine coronary artery bypass surgery. Thirty patients to receive elective coronary artery bypass grafting under cardiopulmonary bypass (CPB) were prospectively randomized into two study groups. Immediate after aortic cross-clamping and just before the application of modified St. Thomas cardioplegic (20 mL/kg), adenosine solution (250 microg/kg) was injected into the aortic root in the study group (n = 15), while the same amount of normal saline injection was administered in the control group (n = 15). Anesthesia was carried out in all patients in a similar fashion, and all the surgeries were performed by the same team. Homodynamic change, cardiac enzyme assay, and post-bypass inotropic supplementation were recorded throughout the study period to evaluate the extent of myocardial ischemic injury. The mean time to asystole after aortic cross-clamping was significantly shorter for the adenosine group compared with the control group (8.1 +/- 5.9 vs. 79.0 +/- 35.3 sec, respectively; P< 0.01). To compare with the baseline value, the mean cardiac index immediately post CPB and 24 hours postoperatively was increased significantly for the adenosine group (from 2.1 +/- 0.6 to 2.6 +/- 0.6 and 3.2 +/- 0.6 L/min/m2, respectively; P < 0.05), as contrasted with the control group (from 2.3 +/- 0.5 to 2.0 +/- 0.4 and 2.5 +/- 0.4 L/min/m2). Further, the requirement for inotropic support after CPB and postoperative troponin I release were significantly less in the adenosine group. There appeared no adverse effects associated with adenosine administration. Immediate administration of 250 microg/kg adenosine via the aortic root following aortic cross-clamping could optimize the myocardial protective effect of conventional cardioplegia, quicken cardiac standstill, and offer better postoperative myocardial performance after CPB.