Document Detail

Direct myocardial effects of levosimendan in humans with left ventricular dysfunction: alteration of force-frequency and relaxation-frequency relationships.
MedLine Citation:
PMID:  17339544     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Enthusiasm for the development of Ca2+ sensitizers as inotropic agents for heart failure has been tempered by reports of impaired relaxation. Levosimendan, which increases myofilament Ca2+ sensitivity via Ca2+-dependent binding to troponin C, exerts positive inotropic and lusitropic effects in failing human myocardium in vitro. We sought to determine the direct effects of levosimendan on failing human myocardium in vivo, and in particular whether levosimendan exerts heart rate-dependent effects on systolic or diastolic function. METHODS AND RESULTS: Ten patients with left ventricular dysfunction caused by nonischemic dilated cardiomyopathy (mean left ventricular ejection fraction, 27+/-2%) were instrumented with an infusion catheter in the left main coronary artery, a high-fidelity micromanometer-tipped catheter in the left ventricle, and a bipolar pacing wire in the right atrium. Inotropic (peak +dP/dt) and lusitropic (Tau) responses were assessed during continuous intracoronary drug infusion in sinus rhythm followed by atrial pacing at 20, 40, and 60 beats per minute above the sinus rate. Under control conditions (intracoronary 5% dextrose in water), atrial-pacing tachycardia decreased Tau by 13% (P<0.05), but did not increase +dP/dt. Intracoronary levosimendan (3.75 and 12.5 microg/min for 15 minutes each) increased +dP/dt dose-dependently and decreased Tau over a range of heart rates, but did not alter the slope of the force-frequency or relaxation-frequency relationship. CONCLUSIONS: Myocardial calcium sensitization with levosimendan exerts mild inotropic and lusitropic effects in humans with left ventricular dysfunction, but does not alter the force-frequency or relaxation-frequency relationship.
Michael M Givertz; Costa Andreou; Chester H Conrad; Wilson S Colucci
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Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-03-05
Journal Detail:
Title:  Circulation     Volume:  115     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2007 Mar 
Date Detail:
Created Date:  2007-03-13     Completed Date:  2007-03-29     Revised Date:  2007-10-11    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1218-24     Citation Subset:  AIM; IM    
Cardiomyopathy Program and Cardiovascular Section, Boston University Medical Center, Boston, Mass, USA.
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MeSH Terms
Cardiac Pacing, Artificial
Cardiomyopathy, Dilated / complications,  drug therapy*,  physiopathology
Cardiotonic Agents / administration & dosage,  pharmacology
Coronary Circulation / drug effects
Dose-Response Relationship, Drug
Heart / drug effects*,  physiopathology
Heart Function Tests / drug effects
Heart Rate / drug effects
Hydrazones / administration & dosage,  pharmacology*
Infusions, Intra-Arterial
Middle Aged
Myocardial Contraction / drug effects*
Pyridazines / administration & dosage,  pharmacology*
Ventricular Dysfunction, Left / drug therapy*,  physiopathology
Reg. No./Substance:
0/Cardiotonic Agents; 0/Hydrazones; 0/Pyridazines; 131741-08-7/simendan
Comment In:
Circulation. 2007 Sep 11;116(11):e346; author reply e347   [PMID:  17846338 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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