Effects of Levosimendan on Hydrogen Peroxide Induced Contraction in Human Saphenous Vein
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Abstract
<b>Aim</b>: Increased oxidative stress plays important roles in vascular dysfunction in patients undergoing coronary artery bypass graft surgery. Hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) 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 H<sub>2</sub>O<sub>2</sub> in human saphenous vein (HSV) segments. <b>Methods</b>: We studied H<sub>2</sub>O<sub>2</sub> induced contractions of isolated HSV mounted in standard tissue baths. H<sub>2</sub>O<sub>2</sub> (10<sup>-6</sup> – 10<sup>-3</sup> M) was added cumulatively to the organ bath. Concentration-response curves to H<sub>2</sub>O<sub>2</sub> were repeated in the presence of levosimendan (10<sup>–8</sup> M). In the second series of experiments, strips were contracted with 5-HT (10<sup>–5</sup> M). When the contraction reached a stable plateau, H<sub>2</sub>O<sub>2</sub> 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 H<sub>2</sub>O<sub>2</sub> . 5-HT produced contractions in SV strips. Further treatment of these strips with H<sub>2</sub>O<sub>2</sub> 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 H<sub>2</sub>O<sub>2</sub> on the 5-HT-induced contraction. <b>Conclusion</b>: 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.
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