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.
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000818:Animals; D002415:Cats; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009201:Myocardial Depressant Factor; D011412:Propanolamines / Q000627:therapeutic use*; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use*; D012771:Shock, Hemorrhagic / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D013999:Timolol / Q000494:pharmacology / Q000627:therapeutic use*
D000319:Adrenergic beta-Antagonists; D009201:Myocardial Depressant Factor; D011412:Propanolamines; D011725:Pyridines; C021276:MK 761; D013999:Timolol; D007545:Isoproterenol