We evaluated the ability of propranolol and dilitazem alone and in combination to enhance the recovery of left ventricular (LV) segmental function during 1 month of reperfusion after two temporary occlusions of the left anterior descending coronary artery (LAD) in conscious dogs instrumented with ultrasonic crystals for the measurement of regional net systolic wall thickening (NET). LV segments were classified according to their contractile function after 1 hr of LAD occlusion: class 1, greater than 67% of preocclusion (control) NET; class 2, 0% to 66.9%; class 3, less than 0% (paradoxical systolic wall thinning). Propranolol (1 mg/kg iv) or diltiazem (20 ,ug/kg/min) was given 65 min after LAD occlusion in dogs that had 2 (group 1) or 4 hr (group II) of LAD occlusion. Diltiazem plus propranolol (same doses) were given to another group of dogs that underwent 4 hr (but not 2) of LAD occlusion. Untreated control dogs received 25 ml of saline and underwent 2 or 4 hr of LAD occlusion. The NET of class 2 and 3 segments in group l control dogs increased significantly during 1 month of reperfusion, from 32 + 5% and -43 ± 6% to 66 + 9% and 26 + 9%, respectively (p < .05). Neither diltiazem nor propranolol enhanced the long-term recovery of these segments in group I dogs. However, diltiazem prevented further deterioration of contractile dysfunction observed in control dogs immediately after reperfusion in both segment classes. The NET of class 2 segments in group I1 control dogs after 4 weeks of reperfusion remained at levels observed during LAD occlusion: 30 + 4% to 37 + 12%. Class 3 NET increased from -33 + 5% to 12 ± 12% with 1 month of reperfusion, but these segments were essentially akinetic. Propranolol or diltiazem alone did not produce significant overall increases in NET, but diltiazem again prevented further declines in NET of class 2 and 3 segments during early reperfusion. However, the combination of diltiazem and propranolol significantly enhanced overall recovery of class 2 NET in group 1I dogs (44 ± 3% to 88 + 7%) and prevented the worsening of NET associated with early reperfusion. Compared with untreated dogs, propranolol plus diltiazem also significantly decreased the extent of histologic necrosis in class 2 and 3 segments as well as the macrohistochemically determined infarct size in group I1 dogs. Propranolol alone caused significant declines in heart rate and LV dP/dtmax; diltiazem alone lowered aortic pressure significantly; aortic pressure and LV dP/dt were lowered by combined propranolol and diltiazem. Thus we conclude that (I) diltiazem alone prevents further deterioration of LV segmental function early after reperfusion following 2 to 4 hr of occlusion, but neither diltiazem nor propranolol alone enhances segmental functional recovery, and (2) the combination of propranolol and diltiazem results in significantly improved recovery of systolic segmental function and a significant reduction in the extent of necrosis in moderately dysfunctional segments after 4 hr of temporary LAD occlusion ...