Effects of Levosimendan on Hydrogen Peroxide Induced Contraction in Human Saphenous Vein

Aim: Increased oxidative stress plays important roles in vascular dysfunction in patients undergoing coronary artery bypass graft surgery. Hydrogen peroxide (H2O2) is used as an experimental model for oxidative stress. The present study was designed to assess the effects of levosimendan pretreatment on the contractile effects induced by H2O2 in human saphenous vein (HSV) segments. Methods: We studied H2O2 induced contractions of isolated HSV mounted in standard tissue baths. H2O2 (10-6 – 10-3 M) was added cumulatively to the organ bath. Concentration-response curves to H2O2 were repeated in the presence of levosimendan (10–8 M). In the second series of experiments, strips were contracted with 5-HT (10–5 M). When the contraction reached a stable plateau, H2O2 was administrated cumulatively into the organ bath. The same procedure was conducted in the presence of levosimendan. Results: Pretreatment of the SV strips with levosimendan significantly reduced the contractile response to each concentration of H2O2 . 5-HT produced contractions in SV strips. Further treatment of these strips with H2O2 resulted in statistically significant concentration-dependent increases in tension. Preincubation of the tissues with levosimendan did not significantly influence the maximum amplitude of the 5-HT-induced tone but inhibited the contractile effect of H2O2 on the 5-HT-induced contraction. Conclusion: Pretreatment of HSV with clinical concentrations of levosimendan inhibits the vasoconstriction caused by oxidative stress, indicating its potential preventive effect against oxidative stress induced graft spasm.