| Bisoprolol delays progression towards right heart failure in experimental pulmonary hypertension. | |
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MedLine Citation:
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PMID: 22157723 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-12-09 |
Journal Detail:
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Title: Circulation. Heart failure Volume: 5 ISSN: 1941-3297 ISO Abbreviation: Circ Heart Fail Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-01-18 Completed Date: 2012-04-13 Revised Date: 2012-05-24 |
Medline Journal Info:
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Nlm Unique ID: 101479941 Medline TA: Circ Heart Fail Country: United States |
Other Details:
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Languages: eng Pagination: 97-105 Citation Subset: IM |
Affiliation:
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Department of Pulmonology, VU University Medical Center/Institute for Cardiovascular Research, Amsterdam, The Netherlands. fs.deman@vumc.nl |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adrenergic beta-1 Receptor Antagonists
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pharmacology,
therapeutic use* Animals Antihypertensive Agents / pharmacology, therapeutic use Bisoprolol / pharmacology, therapeutic use* Disease Models, Animal Disease Progression* Dose-Response Relationship, Drug Echocardiography Fibrosis Heart Failure / etiology*, prevention & control*, ultrasonography Heart Ventricles / pathology, physiopathology, ultrasonography Hypertension, Pulmonary / chemically induced, complications*, drug therapy* Male Monocrotaline / adverse effects Rats Rats, Wistar Signal Transduction / drug effects, physiology Vascular Resistance / drug effects, physiology |
| Chemical | |
Reg. No./Substance:
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0/Adrenergic beta-1 Receptor Antagonists; 0/Antihypertensive Agents; 315-22-0/Monocrotaline; 66722-44-9/Bisoprolol |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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