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• W1999030245 abstract "Most clinical studies have shown that beta-adrenergic receptor antagonists improve long-term survival in heart failure patients. Bucindolol, a nonselective beta-receptor blocker, however, failed to reduce heart failure mortality in a recent large clinical trial. The reasons for this failure are not known. Bucindolol has partial agonist properties in rat myocardium, but whether it has agonist activity in human heart is controversial. To address this, we measured the ability of bucindolol to increase cAMP accumulation in human myocardium.Myocardial strips ( approximately 1 mm(3)) obtained from rat and nonfailing human hearts were confirmed to be viable for > or = 48 hours in normoxic tissue culture by MTT assay and histology. Freshly isolated strips were exposed to beta-adrenergic antagonists and agonists and assayed for cAMP. In both rat and human strips, the full beta-adrenergic agonist isoproterenol raised cAMP levels by >2.5-fold at 15 minutes. Carvedilol and propranolol had no effect on basal cAMP levels, whereas metoprolol reduced basal cAMP by approximately 25%. In contrast, bucindolol and xamoterol increased cAMP levels in a concentration-dependent manner in both rat and human myocardium (maximum 1.64+/-0.25-fold and 2.00+/-0.27-fold over control, respectively, P<0.01 for human tissue).Bucindolol exhibits approximately 60% of the beta-adrenergic agonist activity of xamoterol in normal human myocardial tissue." @default.
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• W1999030245 date "2002-05-21" @default.
• W1999030245 modified "2023-10-16" @default.
• W1999030245 title "Bucindolol Displays Intrinsic Sympathomimetic Activity in Human Myocardium" @default.
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• W1999030245 doi "https://doi.org/10.1161/01.cir.0000016050.79810.18" @default.
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