Potassium Channel-Related Relaxation by Levosimendan in the Human Internal Mammary Artery
Annals of Thoracic Surgery, cilt.81, sa.5, ss.1715-1719, 2006 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 81 Sayı: 5
- Basım Tarihi: 2006
- Doi Numarası: 10.1016/j.athoracsur.2005.12.057
- Dergi Adı: Annals of Thoracic Surgery
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
- Sayfa Sayıları: ss.1715-1719
- Sağlık Bilimleri Üniversitesi Adresli: Evet
Özet
Background: Levosimendan is a potent inotropic and vasodilator drug used in the treatment of decompensated heart failure. There is no study on in vitro effects of levosimendan in human isolated arteries. Methods: We investigated the effect of levosimendan on contractile tone of human isolated internal mammary artery (IMA). The responses in IMA were recorded isometrically by a force-displacement transducer in isolated organ baths. Levosimendan was added to organ baths either at rest or after precontraction with phenylephrine (1 μmol/L). Levosimendan-induced relaxations were tested in the presence of cyclooxygenase inhibitor indomethacin (10 μmol/L), nitric oxide synthase inhibitor N122-nitro-l-arginine methyl ester (100 μmol/L), large-conductance calcium-activated potassium-channel inhibitor tetraethylammonium (1 mmol/L), adenosine triphosphate-sensitive potassium-channel inhibitor glibenclamide (10 μmol/L), and voltage-sensitive potassium-channel inhibitor 4-aminopyridine (1 mmol/L). Results: Levosimendan (10 nmol/L to 3 μmol/L) produced potent relaxation in human IMA (maximal effect, 75.3% ± 4.9% of phenylephrine maximum contraction, 6.8 ± 0.1, n = 15; -log10 of 50% effective concentration). Vehicle had no significant relaxant effect. The relaxation to levosimendan is not affected by either potassium-channel inhibitors (tetraethylammonium and 4-aminopyridine) or cyclooxygenase and nitric oxide synthase inhibitors. Glibenclamide (10 μmol/L) inhibited levosimendan-induced relaxation significantly (p < 0.01). Conclusions: Levosimendan effectively and directly decreases the tone of IMA. The mechanism of levosimendan-induced relaxation in IMA appears in part to be adenosine triphosphate-sensitive potassium-channel opening action. Levosimendan may be a cardiovascular protective agent by its relaxing action on the major arterial graft, IMA. © 2006 The Society of Thoracic Surgeons.