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Prolonged Antispasmodic Effect in Isolated Radial Artery Graft and Pronounced Platelet Inhibition Induced by the Inodilator Drug, Levosimendan.
MedLine Citation:
PMID:  21952040     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Radial artery frequently develops spasm and requires vasodilator therapy during coronary artery bypass graft surgery. Levosimendan was recently shown to oppose 5-hydroxytryptamine-induced contraction of radial artery grafts. The aim of the present study was to explore whether levosimendan retains its vasodilatory capacity following in vitro pre-incubation of radial artery segments with the inodilator. A possible cumulative effect of the drug in human platelets was also studied. Human isolated radial artery segments were pre-incubated in 0.16 μmol L(-1) levosimendan containing solution or in 0.9% NaCl, Bretschneider, 5% albumin and a 5% human serum protein solution (Biseko) as controls for 45 min. Contractions were induced by three consecutive administrations of 5-hydroxytryptamine (0.31 μM) 45, 90 and 120 min. after exchanging the pre-incubation solutions with Krebs-Henseleit solution, uniformly. Receptor-independent contractions (KCl, 80 mmol L(-1) ), endothelium-dependent (acetylcholine, 1 μmol L(-1) ) and independent relaxations (papaverine, 100 μmol L(-1) ) were also investigated. Washed human platelets were pre-incubated with levosimendan (0.06 μmol L(-1) ) for 2 or 15 min. and aggregated with thrombin (0.1 IU mL(-1) ). Contractions of radial artery grafts induced by 5-hydroxytryptamine were significantly smaller 45 min. and 90 min. after the replacement of levosimendan with Krebs-Henseleit solution. Biseko solution also decreased contraction of the graft at 45 min. Contractions did not change in time following the pre-incubations of radial arteries with 0.9% NaCl, Bretschneider and 5% albumin solutions. The grafts remained intact as assessed by their maximum contractions and endothelium-dependent and -independent relaxations at the end of the investigations. Platelets revealed larger anti-aggregatory effect to levosimendan following the enhancement of the incubation time. Results indicate that the antispasmodic and anti-aggregatory effects of levosimendan cumulate in the vascular tissue and in platelets. The storage of radial artery with the inodilator before implantation may help to prevent the intraoperative spasm of the graft and also thrombotic occlusion during coronary artery bypass graft surgery.
Authors:
Nóra Ambrus; Jenő Szolnoky; Piero Pollesello; Attila Kun; András Varró; J Gyula Papp; János Pataricza
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-9-23
Journal Detail:
Title:  Basic & clinical pharmacology & toxicology     Volume:  -     ISSN:  1742-7843     ISO Abbreviation:  -     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-9-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101208422     Medline TA:  Basic Clin Pharmacol Toxicol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.
Affiliation:
University of Szeged, Department of Pharmacology and Pharmacotherapy, Szeged, Hungary University of Szeged, 2nd Department of Internal Medicine and Cardiological Center, Division of Cardiosurgery, Szeged, Hungary Orion Pharma, Cardiology and Critical Care, Espoo, Finland Division of Cardiovascular Pharmacology, Hungarian Academy of Sciences, University of Szeged, Szeged, Hungary.
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