Vasorelaxing effect of levosimendan against 5-hydroxytryptamine-induced contractions in isolated human conduit bypass grafts

Abstract

Levosimendan is a novel inodilator drug developed for the treatment of heart failure. The possible vasodilating property of the drug in human coronary artery bypass grafts was investigated. Isometric tensions of the left internal thoracic artery (LITA, n = 8) as well as the proximal and distal segments of the radial artery (RA, n = 8 and 8) were measured in isolated organ baths. Concentration-relaxation curves for levosimendan (0.009-1.14 μmol L−1) were obtained against 5-hydroxytryptamine (5-HT; serotonin, 0.002–9.3 μmol L 1)-induced contractions. 5-HT-induced contraction of LITA was considerably smaller than that of the proximal and distal RAs. Levosimendan relaxed the grafts in the following order of calculated maximum efficacies (Emax): LITA > proximal RA > distal RA (LITA 100.3 ±16.2% of 5-HT-induced maximum tension, proximal RA 86.9 ±8.6%, distal RA 59.4 ± 17.5%, P < 0.05 LITA vs distal RA). The potency values of levosimendan, expressed as the negative logarithm of 50% effective concentrations (pD2), were comparable in the three bypass grafts (LITA −6.52 ± 0.44 log mol L−1, proximal RA −6.60 ± 0.49 log mol L−1, distal RA −6.85 ± 0.45 log mol L−1). The results suggest that levosimendan is an effective vasorelaxant of conduit bypass grafts and may serve as a new therapeutic tool, especially in the case of LITA and proximal RA grafts, for relieving perioperative spasm and subsequent graft failure.