cardiovascular-agents and bucindolol

This article summarises key presentations relevant to the pathophysiology, prevention or treatment of heart failure, from the Heart Failure Society of America annual meeting held in Toronto, Canada. Data from the EnoxiMone in intravenous inOTropE-dependent subjects (EMOTE) study suggest that the oral PDE-3 inhibitor enoximone may be effective for weaning severe heart failure patients from intravenous inotropic therapy. Hawthorn Extract Randomised Blinded Trial in CHF (HERB-CHF) failed to show a benefit of hawthorn extract added to conventional heart failure therapy. A genetic sub-group analysis of the Blocker Evaluation of Survival Trial (BEST) study showed that bucindolol reduced mortality and hospitalisations in patients who were homozygous for the Arg389 variant of the beta(1) adrenoceptor. In the Resynchronisation Hemodynamic Treatment for Heart Failure Management (RHYTHM-ICD) study, patients randomised to cardiac resynchronisation therapy (CRT) showed an improvement in symptoms and functional capacity compared to the control group.

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Arginine; Cardiotonic Agents; Cardiovascular Agents; Crataegus; Cyclic Nucleotide Phosphodiesterases, Type 3; Enoximone; Enzyme Inhibitors; Exercise Tolerance; Heart Failure; Homozygote; Humans; Oxygen Consumption; Plant Extracts; Propanolamines; Randomized Controlled Trials as Topic; Receptors, Adrenergic, beta-1; Societies, Medical; Stroke Volume; Survival Analysis; Treatment Failure; Treatment Outcome; United States

β-Adrenoceptor antagonists differ in their degree of partial agonism. In vitro assays have provided information on ligand affinity, selectivity, and intrinsic efficacy. However, the extent to which these properties are manifest in vivo is less clear. Conscious freely moving rats, instrumented for measurement of heart rate (β1; HR) and hindquarters vascular conductance (β2; HVC) were used to measure receptor selectivity and ligand efficacy in vivo. CGP 20712A caused a dose-dependent decrease in basal HR (P<0.05, ANOVA) at 5 doses between 6.7 and 670 μg/kg (i.v.) and shifted the dose-response curve for isoprenaline to higher agonist concentrations without altering HVC responses. In contrast, at doses of 67 μg/kg (i.v.) and above, ICI 118551 substantially reduced the HVC response to isoprenaline without affecting HR responses. ZD 7114, xamoterol, and bucindolol significantly increased basal HR (ΔHR: +122 ± 12, + 129 ± 11, and + 59 ± 11 beats/min, respectively; n=6), whereas other β-blockers caused significant reductions (all at 2 mg/kg i.v.). The agonist effects of xamoterol and ZD 7114 were equivalent to that of the highest dose of isoprenaline. Bucindolol, however, significantly antagonized the response to the highest doses isoprenaline. An excellent correlation was obtained between in vivo and in vitro measures of β1-adrenoceptor efficacy (R(2)=0.93; P<0.0001).

Topics: Adrenergic beta-Agonists; Adrenergic beta-Antagonists; Animals; Cardiovascular Agents; CHO Cells; Cricetinae; Cricetulus; Cyclic AMP; Heart Rate; Humans; Imidazoles; Isoproterenol; Male; Phenoxyacetates; Phenoxypropanolamines; Propanolamines; Rats; Rats, Sprague-Dawley; Vascular Resistance; Xamoterol