This study investigated whether nitroglycerin can improve ischemic zone blood flow and function when its infusion is delayed following left anterior descending (LAD) occlusion. Nitroglycerin (200 micrograms/min, 11 dogs) or saline (six dogs) was infused for 2 hours starting 2 hours after occlusion. Regional myocardial blood flow (MBF) was measured (9 +/- 1 micron radioactive microspheres) before and at 2 and 4 hours after occlusion. Segmental contraction was determined by cineroentgenography of implanted tantalum markers. For all ischemic samples (defined as MBF less than or equal to 0.4 ml/min/gm), the average improvement in MBF in the epicardial half (EPI) was 0.05 +/- 0.02 ml/min/gm (mean +/- SEM) with nitroglycerin vs 0.06 +/- 0.06 with saline (p greater than 0.5). Improvement in the endocardial half (ENDO) averaged 0.03 +/- 0.03 ml/min/gm with nitroglycerin vs 0.09 +/- 0.08 with saline (p = 0.5). Contraction in the ischemic zone ceased following occlusion and was unaffected by nitroglycerin or saline. Control blood flows in the ischemic region were 22% less in the ENDO (p less than 0.001) and 19% less in the EPI (p less than 0.005) than in nonischemic myocardium. These results indicate that 2 hours after LAD occlusion in dogs, nitroglycerin was unable to improve ischemic zone collateral flow or contractile function compared to untreated controls. Lower ischemic zone control flows indicate that infarct volume expansion may occur within 4 hours after coronary occlusion.