Reducing blood oxygen affinity may enhance myocardial oxygen delivery during ischemia. We evaluated this hypothesis in awake, previously instrumented dogs that received a 20 ml/kg infusion of a solution of dihydroxyacetone, phosphate, and pyruvate after acute occlusion of either the left anterior descending or circumflex coronary artery. This infusion reduced blood oxygen affinity (BOA) after 2 hours; the P50 increased from 29.9 +/- 0.7 torr (mean +/- SD) to 32.1 +/- 0.6 torr; P less than 0.01 (BOA group). Four dogs received 20 ml/kg of phosphate and pyruvate solution to assess volume effects (V group), and five dogs were controls (C group). The 2-hour P50 values in V and C were unchanged. Regional flow (15-mum spheres) reduction 2 hours postocclusion was compared to the percent tissue infarcted determined by histology 7-9 days after occlusion for multiple samples from the endocardial layer of the left ventricle. When flow was less than 40% of normal, V and C had 55% infarction while BOA had 37% (P less than 0.05); at flow less than 20% of normal, V and C had 79% infarction while BOA had 38% (P less than 0.001); and at less than 10% of normal, V and C 87% and 94% infarction, respectively, while BOA had 56% (P less than 0.001). Reducing blood oxygen affinity after coronary artery occlusion significantly decreased the extent of myocardial necrosis for the same degree of ischemia. Reducing BOA may increase oxygen delivery to ischemic myocardium when flow is restricted.