Atrial pacing (AP) procedure was carried out in 11 cardioischemic patients to reproduce tachycardia-induced myocardial ischemia. Six control subjects underwent the same procedure until the maximum pacing rate was reached. During the procedure, endothelin-1 (ET-1) and plasma lactate levels were measured in the coronary sinus and in the aortic root. In all the patients, atrial pacing provoked electrocardiographic signs and metabolic evidence of myocardial ischemia and a significant decrease (p<0.001) in left ventricular ejection fraction. At AP-induced ischemia, coronary sinus (17.31 +/- 4.20 pg/mL) and arterial (9.60 +/- 3.31 pg/mL) ET-1 plasma levels were significantly different (p<0.001) in the patients. On the contrary, at maximum pacing rate, no significant difference (p=0.186) emerged between coronary sinus (9.72 +/- 1.09 pg/mL) and arterial (8.95 +/- 0.75 pg/mL) plasma ET-1 levels in the control group. These results suggest that, in cardioischemic patients, tachycardia can induce the coronary endothelium to release significant amounts of ET-1.