Comparison of the effects of acute and chronic beta-blockade on infarct size in the dog after circumflex occlusion.

In order to compare the effects of acute and chronic beta-blockade on infact size, the left circumflex coronary artery was occluded for 6 hours in 33 anesthetized dogs. The dogs (18 to 22 kg) were divided into three groups; group 1 (N = 10) served as controls, group 2 received intravenous nadolol (average dose 1.25 mg/kg) just prior to coronary occlusion, and group 3 received oral nadolol (80 mg) twice daily for 16 days prior to coronary occlusion. To ensure equivalent degrees of beta-blockade at the time of occlusion, group 2 and 3 dogs were given incremental doses of intravenous nadolol to abolish the chronotropic response to isoproterenol (2 mu/kg IV). Left ventricular pressure, its first derivative (dP/dt), and heart rate were monitored. The anatomic risk region was determined antemortem by Evan's blue staining while the infarct zone was delineated postmortem by tetrazolium staining. Compared to Group 1, heart rate was 22% lower in group 2 and 15% lower in group 3 dogs 6 hours after occlusion (p less than 0.05). There were no differences among groups in peak left ventricular systolic pressure or mean arterial pressure. Infarct size as a function of the area at risk was 68 +/- 3% in group 1, 52 +/- 7% in group 2, and 44 +/- 8% in group 3. A significant difference was found only between groups 3 and 1. The data suggest that chronic beta-blockade provides greater protection against ischemic-induced necrosis than does acute beta-blockade. The greater protective effect of chronic beta-blockade may be due to chronic adaptive changes in either blood flow or metabolism.