Inhomogeneous delivery of cardioplegic solution may result in postischemic myocardial injury. This study compares the distribution of warm blood antegrade and retrograde cardioplegia to multiple discrete left ventricular myocardial regions in pigs with unobstructed coronary arteries. Cardioplegic solution was delivered antegradely and retrogradely at 150 ml/min, and flows to 1152 individual myocardial regions were determined twice for each route with four different radiolabeled microspheres. The antegrade system delivered greater flow to each gram of myocardium than did the retrograde system (1.37 +/- 0.31 versus 0.39 +/- 0.09 ml/gm per minute, p < 0.001). Flow to individual myocardial regions was significantly inhomogeneous for both antegrade and retrograde cardioplegia, but much more so for retrograde cardioplegia (coefficient of variation was 48% +/- 17% for antegrade cardioplegia and 106% +/- 16% for retrograde cardioplegia; p < 0.001). The pattern of how to individual myocardial regions was highly reproducible for a given route of delivery as confirmed by repeated measurements with different radioactive microsphere isotopes (correlation coefficients 0.88 +/- 0.12 for AC(1) - AC(2) and 0.84 +/- 0.10 RC(1) - RC(2)), but antegrade cardioplegia and retrograde cardioplegia patterns were significantly different and therefore complementary (correlation coefficients 0.03 +/- 0.04, p < 0.001). These findings support the routine combined use of antegrade cardioplegia and retrograde cardioplegia to enhance delivery of cardioplegic solution to all regions of the heart and minimize the potential risk of postischemic myocardial dysfunction.