This study compares the protection provided by prolonged (4 hours) aortic clamping with glutamate-enriched potassium blood cardioplegia (n = 8) to (1) prolonged (4 hours) aortic clamping with multidose potassium blood cardioplegia without glutamate (n = 4), (2) 4 hours of continuous perfusion of the beating empty heart (n = 7), and (3) 15 minutes of normothermic ischemia (n = 10). According to measurements of myocardial oxygen uptake, left ventricular compliance, left ventricular contractility, and stroke work performance, no statistical difference could be detected between those hearts receiving blood cardioplegia either with or without glutamate enrichment. In both of these groups, myocardial protection was excellent, as demonstrated by the following: postischemic myocardial oxygen uptake 43% (p less than 0.05) above control, 95% +/- 6% recovery of the left ventricular compliance, a 97% +/- 5% return of the left ventricular contractility, and a 91% +/- 6% recovery of stroke work index. Contrary to the excellent recovery of those hearts receiving blood cardioplegic protection, those hearts undergoing 4 hours of continuous perfusion showed a 45% +/- 16% (p less than 0.05) loss of left ventricular compliance and a 72% +/- 8% (p less than 0.05) recovery of stroke work index; those hearts experiencing 15 minutes of normothermic ischemia showed a 74% +/- 6% (p less than 0.05) return of left ventricular compliance, a 30% +/- 5% (p less than 0.05) decrease in contractility, and a 56% +/- 5% (p less than 0.05) recovery of postischemic left ventricular stroke work.