Studies of controlled reperfusion after ischemia. XXIII. Deleterious effects of simulated thrombolysis preceding simulated coronary artery bypass grafting with controlled blood cardioplegic reperfusion. This study tests whether simulated thrombolysis before controlled reperfusion (i.e., simulated coronary artery bypass) causes reperfusion injury that obviates the benefits of subsequent controlled reperfusion and results in unnecessary ventricular arrhythmias. Fifteen dogs underwent acute occlusion of the left anterior descending coronary artery. In 10 dogs we simulated thrombolysis after 1 hour of ischemia (delivering 10% to 15% of control flow at 5 ml/min), followed 1 hour later by either normal blood reperfusion at systemic pressure (to simulate percutaneous transluminal coronary angioplasty) in five dogs or regionally controlled blood cardioplegic reperfusion on bypass in five others to simulate coronary bypass. In five dogs ischemia was prolonged to 2 hours, and the initial reperfusate was blood cardioplegic solution on total vented bypass (to simulate primary coronary bypass). All hearts receiving simulated thrombolysis (100%) after 1 hour of ischemia had reperfusion-induced ventricular fibrillation. All hearts treated by simulated angioplasty recovered regional contractility (56% of control systolic shortening), whereas there was no (0%) recovery of spontaneous contractility after subsequent blood cardioplegic reperfusion, and only two (40%) dogs had contractile reserve capacity (6% +/- 49%). Conversely, surgically controlled blood cardioplegic reperfusion without preceding low-flow normal blood reperfusion after 2 hours of ischemia resulted in no ventricular arrhythmias (0%; p less than 0.05 versus simulated coronary artery bypass after simulated thrombolysis), 72% +/- 7% (p less than 0.05 versus simulated coronary artery bypass after simulated thrombolysis) recovery of regional contractility (ultrasonic crystals), and 114% +/- 11% (p less than 0.05 versus simulated coronary artery bypass after simulated thrombolysis) recovery of contractile reserve with calcium chloride stimulation. We conclude that controlled reperfusion (simulating coronary artery bypass) with blood cardioplegic solution produces immediate functional recovery and avoids the ventricular fibrillation that follows simulated thrombolysis despite the need for prolonged ischemic time. Preceding controlled reperfusion by normal blood reperfusion (simulated thrombolysis) shortens the ischemic time but nullifies immediate functional recovery possible by simulated coronary bypass and produces unnecessary arrhythmias. 