Three myocardial protection techniques were studied in a canine model of acute myocardial ischemia with subsequent revascularization. Eighteen animals were randomly assigned to one of three treatment regimens: cold oxygenated crystalloid cardioplegia (CC), cold blood cardioplegia with modified reperfusate (CB), and continuous aerobic warm blood cardioplegia (WB) (n = 6 per group). Systemic hypothermic cardiopulmonary bypass (28 degrees C), antegrade arrest, and intermittent retrograde and antegrade delivery were used for the CC and CB groups. Systemic normothermic cardiopulmonary bypass, antegrade arrest, and continuous retrograde delivery were used for the WB group. Fifteen minutes of warm global ischemia was followed by occlusion of the left anterior descending coronary artery (15-minute duration) and simultaneous initiation of cardioplegic arrest (60-minute duration) to simulate clinical revascularization. After reperfusion, the animals were separated from cardiopulmonary bypass. Myocardial function, electrocardiogram, myocardial energetics, water content, histopathology, and defibrillation requirements were compared between groups. There was no significant difference in maximum elastance, myocardial oxygen consumption, myocardial edema, or histopathologic evidence of injury between groups. However, overall ventricular function, assessed by the slope of the preload recruitable stroke work relationship, was significantly better for the WB group (p = 0.04) (WB, 73 +/- 9; CB, 56 +/- 7; CC, 47 +/- 5). Diastolic function as assessed by the slope of the stress-strain relationship was significantly worse overall for the cold groups (p = 0.001) (WB, 20 +/- 2.2; CB, 39 +/- 1.3; CC, 37 +/- 3.1). Myocardial injury as assessed by ST segment elevation (millimeters) was less for the WB group (p = 0.03) (WB, 0.4 +/- 0.3; CB, 1.7 +/- 0.2; CC, 1.6 +/- 0.7). Countershocks necessary to restore sinus rhythm after cross-clamp removal were fewer in the WB group (p = 0.03) (WB, 0.8 +/- 0.3; CB, 4.0 +/- 1.2; CC, 5.5 +/- 1.5). In this model of acute global myocardial ischemia, continuous aerobic warm blood cardioplegia has important advantages over two widely used clinical hypothermic protection techniques.