Effects of levosimendan on isolated human internal mammary artery and saphenous vein: concurrent use with conventional vasodilators

• Published in: Fundamental & clinical pharmacology Vol. 30; no. 3; pp. 226 - 234
• Main Authors: Ertuna, Elif, Turkseven, Saadet, Amanvermez, Dilsad, Ayik, Fatih, Yagdi, Tahir, Yasa, Mukadder
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.06.2016
• Subjects: Dose-Response Relationship, Drug; Drug Interactions - physiology; Drug Therapy, Combination; Female; graft spasm; human internal mammary artery; human saphenous vein; Humans; Hydrazones - administration & dosage; Hydrazones - metabolism; levosimendan; Male; Mammary Arteries - drug effects; Mammary Arteries - physiology; Middle Aged; Organ Culture Techniques; Papaverine - administration & dosage; Papaverine - metabolism; Pyridazines - administration & dosage; Pyridazines - metabolism; Saphenous Vein - drug effects; Saphenous Vein - physiology; Vasoconstriction - drug effects; Vasoconstriction - physiology; Vasoconstrictor Agents - administration & dosage; Vasoconstrictor Agents - metabolism; Vasodilator Agents - administration & dosage; Vasodilator Agents - metabolism; levosimendan; human internal mammary artery; human saphenous vein; graft spasm
• ISSN: 0767-3981; 1472-8206
• DOI: 10.1111/fcp.12185

Graft spasm is a common problem in coronary artery bypass grafting (CABG). In this study, we aimed to investigate the interaction of levosimendan, a novel inodilator, with vasodilator agents that are clinically used for the treatment of graft spasm and with endogenous vasoconstrictors that are thought to play a role in graft vasospasm, in human internal mammary artery (IMA) and saphenous vein (SV). Isolated human IMA and SV segments derived from patients undergoing CABG were suspended in an organ bath. Responses to cumulative concentrations of noradrenaline (NA), serotonin (5‐HT), papaverine, nitroglycerin (NG), and diltiazem were recorded before and after 10−5 m levosimendan incubation (30 min). In addition, cumulative levosimendan responses were taken in vessels precontracted with NA or 5‐HT. 10−5 m levosimendan reduced NA Emax and sensitivity in IMA and SV, and 5‐HT Emax responses in IMA. Moreover, levosimendan caused concentration‐dependent relaxation in both grafts. Papaverine Emax or sensitivity was not altered by levosimendan neither in IMA nor in SV. Levosimendan diminished NG sensitivity in IMA and Emax responses in SV and decreased diltiazem Emax responses both in IMA and SV. Our results suggest that levosimendan may be used alone for prevention or treatment of graft spasm in IMA or in combination with papaverine in IMA and SV grafts. However, as concurrent administration with diltiazem or NG causes a reduction in relaxation in vitro, we suggest caution should be exercised when using levosimendan in combination with these agents.