Enhancement of myocardial recovery with glutamate-enriched cold blood potassium cardioplegia (BPC) was evaluated using an isolated working heart model. Three groups of hearts from immature rabbits were subjected to 20 minutes of warm (37 degrees C) ischemia to allow energy depletion, followed by 90 minutes of hypothermic (10 degrees C) ischemia. Myocardial protection provided during hypothermia consisted of cardioplegia infusion, at 50 mm Hg every 30 minutes at 4 degrees C, of either St. Thomas' Hospital solution (group 1, n = 6), oxygenated BPC (group 2, n = 7), or oxygenated BPC enriched with 20 mmol/L L-glutamate (group 3, n = 7). Percent recovery of aortic flow was 87.6% +/- 6.3% (results expressed as mean +/- standard error of the mean) in group 3, which was significantly better than for either group 1 (63.4% +/- 4.0%) or group 2 (47.0% +/- 3.5%) (p < 0.05 by analysis of variance). Group 3 hearts had significantly better recovery of myocardial energy stores (mumol/g dry weight) compared with group 1 or 2 hearts: adenosine triphosphate, 17.8 +/- 1.1 versus 12.4 +/- 1.5 and 12.1 +/- 0.4; creatine phosphate, 25.9 +/- 1.8 versus 17.8 +/- 1.8 and 20.3 +/- 0.7; and glycogen, 140.7 +/- 12.6 versus 98.7 +/- 9.9 and 60.7 +/- 9.9 (p < 0.05). Glutamate-enriched BPC provided excellent myocardial protection after ischemia in this immature model, and this study quantitatively supports the use of glutamate-enriched BPC in neonatal clinical practice.