Actions of non-cardiodepressant beta-adrenergic blocking agents in hemorrhagic shock

Two new beta-adrenergic blocking agents, timolol and MK-761, were found to effectively antagonize the positive inotropic effects of isoproterenol on isolated cat papillary muscles without depressing contractile force. However, appropriate doses of these beta-adrenergic blockers (ie, 12.5--25 microgram/kg) did not significantly prolong survival in hemorrhagic shock in anesthetized cats. MK-761 prevented some of the plasma accumulations of myocardial depressant factor (MDF) during shock. Nevertheless both beta-blockers failed to prevent the accumulation of the lysosomal protease cathepsin D or peptide fragments (ie, amino-nitrogen groups) in the blood during shock. We conclude that neither agent is of significant benefit in severe hemorrhagic shock, and probably beta-adrenergic blockade is not a productive approach to pursue in the therapeutics of hemorrhagic shock.