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  • Title: Beta-blockade and ischaemic injury: effects of partial agonist activity.
    Author: Manning AS, Keogh JM, Hearse DJ, Coltart DJ.
    Journal: Cardiovasc Res; 1980 Dec; 14(11):619-23. PubMed ID: 7226171.
    Abstract:
    In this study we have attempted: firstly to assess the extent to which the presence of partial agonist activity in a beta-blocking compound and/or sympathetic drive, influence ischaemic injury, and secondly to determine if any of the observed differences are due to changes in contractile activity. In the isolated, globally ischaemic (low flow) rat heart, oxprenolol (which possesses partial agonist activity) did not reduce creatine kinase leakage to the same extent as propranolol (no partial agonist activity) regardless of the background level of catecholamine drive. However, increasing background catecholamine drive increased the relative protection against enzyme leakage, of both beta-blockers. Under conditions of zero contractile activity (high K+ - medium) neither beta-blocker reduced enzyme leakage. Thus at equi-blocking doses oxprenolol and propranolol reduce enzyme leakage to different extents and the lesser protection afforded by oxprenolol is likely to be attributed to the presence of partial agonist activity. In addition, the reduction in enzyme leakage caused by both these compounds is due to reductions in contractile activity.
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