Reperfusion after 2 hr of experimental ischemia results in reduced blood flow to the reperfused region, as well as elevated regional O2 extraction in that region. The aim of the present study was to determine whether diltiazem, administered during reperfusion, can improve regional blood flow and lower O2 extraction in the previously occluded region. In open-chest anesthetized dogs, 2-hr occlusion of the left anterior descending coronary artery was followed by a 4-hr period of reperfusion. In 7 of the 15 animals, diltiazem (0.45 micrograms/kg/min) was infused i.v. during the reperfusion period; this was preceded by a loading dose of 0.18 micrograms/kg 10 min before release. Small artery and vein O2 saturations obtained microspectrophotometrically were combined with regional blood flow measurements using radioactive microspheres to determine regional myocardial O2 consumption. In both groups, coronary occlusion lowered regional flow to a similar level. After a 4-hr reperfusion, flow to the subendocardial region of treated hearts was significantly greater than that to the untreated reperfused myocardium (75.6 +/- 46.4 vs. 40.3 +/- 25.8 ml/min/100 g), and did not differ from the preocclusion level. The subendocardium/subepicardium flow ratio was reversed in occluded and untreated reperfused myocardium (subendocardium flow less than subepicardium flow), but was not reversed in treated reperfused regions. Myocardial oxygen extraction was 11.0 +/- 2.4 ml of O2/100 ml of blood in the untreated reperfused subendocardium, and was significantly decreased to 8.5 +/- 0.9 ml of O2/100 ml in the treated subendocardium. The proportion of individual veins having O2 saturations below 25% was significantly reduced by diltiazem treatment from 45.2 to 22.7%.(ABSTRACT TRUNCATED AT 250 WORDS)