Warm blood cardioplegia has emerged as a substitute for cold blood cardioplegia as a method of myocardial protection. However, the continuous infusion of blood in this technique may obscure the operative field and necessitate interruption of warm blood cardioplegia. This experimental study was therefore undertaken to determine whether interrupting warm blood cardioplegia during coronary revascularization would increase myocardial damage. In 30 adult pigs, the second and third diagonal vessels were occluded with snares for 90 minutes. All animals underwent cardiopulmonary bypass and 45 minutes of cardioplegic arrest. During the period of cardioplegic arrest, 10 pigs received intermittent antegrade/retrograde infusion of cold blood cardioplegic solution (4 degrees C) 10 pigs received continuous retrograde infusion of warm blood cardioplegic solution (37 degrees C) at 100 ml/min, and 10 pigs received retrograde infusion of warm blood cardioplegic solution that was interrupted for three 7-minute periods. After aortic unclamping, the coronary snares were released and all hearts were reperfused for 180 minutes. Interrupting retrograde warm blood cardioplegia resulted in more tissue acidosis during cardioplegic arrest (6.20 +/- 0.16 interrupted retrograde warm blood cardioplegia and 6.45 +/- 0.12 continuous retrograde warm blood cardioplegia, both p < 0.05 compared with 6.98 +/- 0.17 intermittent antegrade and retrograde cold blood cardioplegia), decreased echocardiographic wall-motion scores (4 [normal] to -1 [dyskinesis]; 2.06 +/- 0.30 interrupted retrograde warm blood cardioplegia, p < 0.05 compared with 3.30 +/- 0.40 intermittent antegrade and retrograde cold blood cardioplegia, 2.80 +/- 0.40 continuous retrograde warm blood cardioplegia), and increased tissue necrosis as measured by the area of necrosis/area at risk (38% +/- 5% interrupted retrograde warm blood cardioplegia, p < 0.05 compared with 21% +/- 2% intermittent antegrade and retrograde cold blood cardioplegia; 25% +/- 2% continuous retrograde warm blood cardioplegia). We concluded that interrupting warm blood cardioplegia during coronary revascularization diminishes the effectiveness of warm blood cardioplegia and results in increased ischemic damage.