Prolonged Antispasmodic Effect in Isolated Radial Artery Graft and Pronounced Platelet Inhibition Induced by the Inodilator Drug, Levosimendan

Nóra Ambrus, Jeno A. Szolnoky, Piero Pollesello, Attila Kun, András Varró, J. Gyula Papp, János Pataricza

Research output: Article

11 Citations (Scopus)

Abstract

Radial artery frequently develops spasm and requires vasodilator therapy during coronary artery bypass graft surgery (CABG). Levosimendan was recently shown to oppose 5-hydroxytryptamine-induced contraction of radial artery (RA) grafts. The aim of the present study was to explore whether levosimendan retains its vasodilatory capacity following in vitro pre-incubation of RA segments with the inodilator. A possible cumulative effect of the drug in human platelets was also studied. Human isolated RA segments were pre-incubated in 0.16μmol/L levosimendan containing solution or in 0.9% NaCl, Bretschneider, 5% albumin and a 5% human serum protein solution (Biseko) as controls for 45min. Contractions were induced by three consecutive administrations of 5-hydroxytryptamine (0.31μM) 45, 90 and 120min. after exchanging the pre-incubation solutions with Krebs-Henseleit solution, uniformly. Receptor-independent contractions (KCl, 80mmol/L), endothelium-dependent (acetylcholine, 1μmol/L) and independent relaxations (papaverine, 100μmol/L) were also investigated. Washed human platelets were pre-incubated with levosimendan (0.06μmol/L) for 2 or 15min. and aggregated with thrombin (0.1IU/mL). Contractions of RA grafts induced by 5-hydroxytryptamine were significantly smaller 45min. and 90min. after the replacement of levosimendan with Krebs-Henseleit solution. Biseko solution also decreased the contraction of the graft at 45min. 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 endothelium-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 RA with the inodilator before implantation may help to prevent the intraoperative spasm of the graft and also thrombotic occlusion during CABG surgery.

Original languageEnglish
Pages (from-to)269-274
Number of pages6
JournalBasic and Clinical Pharmacology and Toxicology
Volume110
Issue number3
DOIs
Publication statusPublished - márc. 1 2012

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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