Document Detail


Electrophysiologic effects of a calcium sensitizer inotrope levosimendan administered intravenously in patients with normal cardiac function.
MedLine Citation:
PMID:  10774799     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Provocation of fatal cardiac arrhythmias has limited the use of inotropic agents as heart failure therapy. Calcium sensitization of the myofilaments might increase inotropy without influencing cardiac electrophysiology unless modified by ancillary properties of the drugs. Electrophysiologic effects of a calcium sensitizer inotrope levosimendan were examined in short-term intravenous administration in humans. Variables were determined in 10 patients with normal cardiac function during a preceding control phase and levosimendan infusion yielding a high therapeutic concentration of 110 (+/-22) microg/L. Levosimendan increased heart rate by 9 beats/min (p < 0.01) on average and shortened the sinus node recovery time and AH interval. At the tested cycle lengths, levosimendan shortened the effective refractory periods in the atrioventricular node by 40-63 ms (p < 0.05), in the atrium by 22-33 ms (p < 0.001), and in the ventricle by 5-9 ms (p < 0.005) on average. Levosimendan increased ventricular monophasic action potential duration by 9-17 ms at 50% (p < 0.001) and by 5-15 ms (p = 0.07) at 90% levels of repolarization on average. The QT interval during spontaneous rhythm and atrial pacing remained unchanged although increased slightly when corrected to sinus rate (p < 0.001). The observations indicate that levosimendan in short-term administration facilitates impulse formation and conduction in cardiac slow-response tissue, enhances recovery of excitability in the myocardium, and may delay ventricular repolarization. The effects on the ventricle were not substantial, and therefore the likelihood of provoking serious cardiac arrhythmias is not estimated to be high.
Authors:
L Toivonen; M Viitasalo; S Sundberg; J Akkila; L Lehtonen
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Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  35     ISSN:  0160-2446     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  2000 Apr 
Date Detail:
Created Date:  2000-08-16     Completed Date:  2000-08-16     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  664-9     Citation Subset:  IM    
Affiliation:
Division of Cardiology, Helsinki University Central Hospital, Finland. lauri.toivonen@huch.fi
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MeSH Terms
Descriptor/Qualifier:
Action Potentials / drug effects
Adult
Calcium / metabolism
Cardiotonic Agents / pharmacology*
Electrophysiology
Female
Heart / drug effects*
Heart Function Tests
Humans
Hydrazones / pharmacology*
Injections, Intravenous
Male
Pyridazines / pharmacology*
Vasodilator Agents / pharmacology
Ventricular Function / drug effects
Chemical
Reg. No./Substance:
0/Cardiotonic Agents; 0/Hydrazones; 0/Pyridazines; 0/Vasodilator Agents; 131741-08-7/simendan; 7440-70-2/Calcium

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


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