Document Detail

The effects of combined versus selective adrenergic blockade on left ventricular and systemic hemodynamics, myocardial substrate preference, and regional perfusion in conscious dogs with dilated cardiomyopathy.
MedLine Citation:
PMID:  16682315     Owner:  NLM     Status:  MEDLINE    
OBJECTIVES: Given that adverse effects of chronic sympathetic activation are mediated by all three adrenergic receptor subtypes (beta1, beta2, alpha1), we examined the effects of standard doses of carvedilol and metoprolol succinate (metoprolol controlled release/extended release [CR/XL]) on hemodynamics, myocardial metabolism, and regional organ perfusion.
BACKGROUND: Both beta1 selective and combined adrenergic blockade reduce morbidity and mortality in heart failure. Whether there are advantages of one class over the other remains controversial, even in the wake of the Carvedilol Or Metoprolol European Trial (COMET). Similarly, the mechanistic basis for the relative differences is incompletely understood.
METHODS: Thirty-three conscious, chronically instrumented dogs with pacing-induced (240 min(-1) for 4 weeks) dilated cardiomyopathy (DCM) were randomized to carvedilol (25 mg twice daily, Coreg, Glaxo Smith Kline, Research Triangle, North Carolina) or metoprolol succinate (100 mg qd, Toprol XL, Astra Zeneca, Wilmington, Delaware). Left ventricular and systemic hemodynamics, myocardial substrate uptake, and norepinephrine spillover were measured before and after three days of treatment. Regional (renal, hepatic, skeletal muscle) blood flows were measured using neutron-activated microspheres.
RESULTS: Both agents had comparable heart rate effects. However, carvedilol-treated dogs showed significantly greater increases in stroke volume and cardiac output and decreases in left ventricular end-diastolic pressure and systemic vascular resistance. Carvedilol increased renal, hepatic, and skeletal muscle blood flow. Carvedilol increased myocardial glucose uptake and suppressed norepinephrine and glucagon. Carvedilol antagonized the response to exogenous norepinephrine to a greater extent than metoprolol CR/XL.
CONCLUSIONS: At doses inducing comparable heart rate reductions, short-term treatment with carvedilol had superior hemodynamic and metabolic effects compared with metoprolol CR/XL. These data suggest important advantages of blocking all three adrenergic receptor subtypes in DCM.
Lazaros A Nikolaidis; Indu Poornima; Pratik Parikh; Megan Magovern; You-Tang Shen; Richard P Shannon
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2006-04-17
Journal Detail:
Title:  Journal of the American College of Cardiology     Volume:  47     ISSN:  1558-3597     ISO Abbreviation:  J. Am. Coll. Cardiol.     Publication Date:  2006 May 
Date Detail:
Created Date:  2006-05-09     Completed Date:  2006-05-23     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  8301365     Medline TA:  J Am Coll Cardiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1871-81     Citation Subset:  AIM; IM    
Department of Medicine, Allegheny General Hospital, Pittsburgh, Pennsylvania 15212, USA.
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MeSH Terms
Adrenergic Antagonists / therapeutic use*
Adrenergic beta-Agonists / pharmacology
Carbazoles / therapeutic use*
Cardiomyopathy, Dilated / drug therapy*,  metabolism,  physiopathology
Heart Rate / drug effects
Hemodynamics / drug effects*
Isoproterenol / pharmacology
Metoprolol / analogs & derivatives*,  therapeutic use
Myocardium / metabolism*
Propanolamines / therapeutic use*
Regional Blood Flow / drug effects
Ventricular Function, Left / drug effects*
Grant Support
Reg. No./Substance:
0/Adrenergic Antagonists; 0/Adrenergic beta-Agonists; 0/Carbazoles; 0/Propanolamines; 0K47UL67F2/carvedilol; 37350-58-6/Metoprolol; 7683-59-2/Isoproterenol; TH25PD4CCB/metoprolol succinate

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