The effect of beta blockade and partial agonist activity during myocardial ischemia

In this study, we have investigated the importance of partial agonist activity during myocardial ischemia by comparing the effects of equiblocking doses of oxprenolol, which possesses partial agonist activity, to propranolol which does not. In the isolated, globally ischemic (low-flow) rat heart, when propranolol or oxprenolol was added alone during the ischemic period, only propranolol reduced enzyme leakage relative to control. However, when the hearts were perfused (10 min) prior to ischemia with these drugs, both beta blockers caused a significant reduction in enzyme leakage. Under conditions of enhanced sympathetic drive (in the presence of 0.01 microM isoproterenol), both beta blockers reduced enzyme leakage to differing extents. In hearts with low sympathetic drive (reserpine pretreatment), enzyme leakage was unaffected by propranolol and exacerbated by oxprenolol. The results of this study suggest that oxprenolol and propranolol influence ischemic damage to differing extents and that this difference is due to partial agonist activity. Also, the protective action of all beta-blocking compounds depends greatly on the background level of sympathetic drive.