Document Detail

Bisoprolol delays progression towards right heart failure in experimental pulmonary hypertension.
MedLine Citation:
PMID:  22157723     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: In pulmonary arterial hypertension (PH), sympathetic adrenergic activity is highly elevated. Sympathetic overactivity is a compensatory mechanism at first, but might be detrimental for cardiac function in the long run. We therefore investigated whether chronic low-dose treatment with bisoprolol (a cardioselective β-blocker) has beneficial effects on cardiac function in experimental PH.
METHODS AND RESULTS: PH was induced in rats by a single injection of monocrotaline (60 mg/kg). Pressure telemetry in PH rats revealed that 10 mg/kg bisoprolol was the lowest dose that blunted heart rate response during daily activity. Ten days after monocrotaline injection, echocardiography was performed and PH rats were randomized for bisoprolol treatment (oral gavage) or vehicle (n=7/group). At end of study (body mass loss >5%), echocardiography was repeated, with additional pressure-volume measurements and histomolecular analyses. Compared with control, right ventricular (RV) systolic pressure and arterial elastance (measure of vascular resistance) more than tripled in PH. Bisoprolol delayed time to right heart failure (P<0.05). RV afterload was unaffected, however, bisoprolol treatment increased RV contractility and filling (both P<0.01), and partially restored right ventriculo-arterial coupling and cardiac output (both P<0.05). Bisoprolol restored RV β-adrenergic receptor signaling. Histology revealed significantly less RV fibrosis and myocardial inflammation in bisoprolol treated PH rats.
CONCLUSIONS: In experimental PH, treatment with bisoprolol delays progression toward right heart failure, and partially preserves RV systolic and diastolic function. These promising results suggest a therapeutic role for β-blockers in PH that warrants further clinical investigation.
Frances S de Man; M Louis Handoko; Joris J M van Ballegoij; Ingrid Schalij; Sylvia J P Bogaards; Pieter E Postmus; Jolanda van der Velden; Nico Westerhof; Walter J Paulus; Anton Vonk-Noordegraaf
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-12-09
Journal Detail:
Title:  Circulation. Heart failure     Volume:  5     ISSN:  1941-3297     ISO Abbreviation:  Circ Heart Fail     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-01-18     Completed Date:  2012-04-13     Revised Date:  2012-05-24    
Medline Journal Info:
Nlm Unique ID:  101479941     Medline TA:  Circ Heart Fail     Country:  United States    
Other Details:
Languages:  eng     Pagination:  97-105     Citation Subset:  IM    
Department of Pulmonology, VU University Medical Center/Institute for Cardiovascular Research, Amsterdam, The Netherlands.
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MeSH Terms
Adrenergic beta-1 Receptor Antagonists / pharmacology,  therapeutic use*
Antihypertensive Agents / pharmacology,  therapeutic use
Bisoprolol / pharmacology,  therapeutic use*
Disease Models, Animal
Disease Progression*
Dose-Response Relationship, Drug
Heart Failure / etiology*,  prevention & control*,  ultrasonography
Heart Ventricles / pathology,  physiopathology,  ultrasonography
Hypertension, Pulmonary / chemically induced,  complications*,  drug therapy*
Monocrotaline / adverse effects
Rats, Wistar
Signal Transduction / drug effects,  physiology
Vascular Resistance / drug effects,  physiology
Reg. No./Substance:
0/Adrenergic beta-1 Receptor Antagonists; 0/Antihypertensive Agents; 315-22-0/Monocrotaline; 66722-44-9/Bisoprolol

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