Hypothermia is widely acknowledged to be the fundamental component of myocardial protection during cardiac operations. Although it prolongs the period of ischemic arrest by reducing oxygen demands, hypothermia is associated with a number of major disadvantages, including its detrimental effects on enzymatic function, energy generation, and cellular integrity. We hypothesized that the ideal protected state of the heart would be electromechanically arrested and perfused with blood, that is, aerobic arrest. Under these conditions the fundamental need for hypothermia becomes questionable. We have developed a novel approach to myocardial protection during cardiac operations based on these concepts, in which the chemically arrested heart is perfused continuously with blood and maintained at 37 degrees C. In 121 consecutive coronary bypass procedures we have compared this approach with a historical cohort of 133 consecutive patients treated with hypothermic cardioplegia. Perioperative myocardial infarction was significantly less prevalent (1.7% versus 6.8%; p less than 0.05) in the warm cardioplegic group, as was the use of the intraaortic balloon pump (0.9% versus 9.0%; p less than 0.005) and the prevalence of low output syndrome (13.5% versus 3.3%; p less than 0.005). Cardiac output immediately after bypass was significantly higher than before bypass (3.1 +/- 0.9 versus 4.9 +/- 1.0 L/min; p less than 0.001) only in the warm cardioplegia group. Furthermore, the heartbeat in 99.2% of patients treated with continuous warm cardioplegia converted to normal sinus rhythm spontaneously after removal of the aortic crossclamp compared with only 10.5% of the hypothermic group. The time from removal of the aortic crossclamp to discontinuation of cardiopulmonary bypass (i.e., reperfusion time) was significantly shorter in the warm cardioplegia group (11 +/- 4.3 versus 27 +/- 5.6 minutes; p less than 0.001). Our results suggest that continuous normothermic blood cardioplegia is safe and effective. Conceptually, this represents a new approach to the problem of maintaining excellent myocardial preservation during cardiac operations.