To determine the safety and efficacy of synchronized coronary venous retroperfusion during brief periods of ischemia, 30 patients undergoing angioplasty of the left anterior descending coronary artery were studied. Each patient underwent a minimum of two angioplasty balloon inflations. Alternate dilations were supported with retroperfusion; the unsupported inflations served as the control inflations. Synchronized retroperfusion was performed by pumping autologous femoral artery blood by means of an electrocardiogram-triggered retroperfusion pump into the great cardiac vein through a triple lumen 8.5F balloon-tipped retroperfusion catheter inserted percutaneously from the right internal jugular vein. Clinical symptoms, hemodynamics and two-dimensional echocardiographic wall motion abnormalities were analyzed. Retroperfusion was associated with a lower angina severity score (0.8 +/- 1 vs. 1.2 +/- 1) and delay in onset of angina (53 +/- 31 vs. 37 +/- 14 s; p less than 0.05) compared with the control inflations. The magnitude of ST segment change was 0.11 +/- 0.14 mV with retroperfusion and 0.16 +/- 0.17 mV without treatment (p less than 0.05). The severity of left ventricular wall motion abnormality was also significantly (p less than 0.01) reduced with retroperfusion compared with control (0.7 +/- 1.4 [hypokinesia] vs. -0.3 +/- 1.6 [dyskinesia]). There were no significant changes in hemodynamics, except in mean coronary venous pressure, which increased from 8 +/- 3 mm Hg at baseline to 13 +/- 6 mm Hg with retroperfusion. Four patients required prolonged retroperfusion for treatment of angioplasty-induced complications. The mean retroperfusion duration in these patients was 4 +/- 2 h (range 2 to 7). In the three patients who underwent emergency bypass surgery, the coronary sinus was directly visualized during surgery and found to be without significant injury. There were no major complications. Minor adverse effects were transient atrial fibrillation (n = 2), jugular venous catheter insertion site hematomas (n = 4) and atrial wall staining (n = 1), all of which subsided spontaneously. Thus, retroperfusion significantly reduced and delayed the onset of coronary angioplasty-induced myocardial ischemia and provided effective supportive therapy for failed and complicated angioplasty.