Abstract
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.
Highlights
Human saphenous vein is frequently used for coronary artery bypass grafting because of ready availability and suppleness [1]
2) Pretreatment with levosimendan (10–8 M) prevents contractile responses caused by H2O2 in the tissues precontracted with 5-HT but does not affect 5-HT elicited contractions
In order to evaluate the effect of levosimendan on vasoconstriction during oxidative stress, first we tested the effect of levosimendan with incubation on cumulative H2O2 concentration response curve in human saphenous vein (HSV) strips at resting tension
Summary
Human saphenous vein is frequently used for coronary artery bypass grafting because of ready availability and suppleness [1]. Vasospasm of the graft following coronary artery bypass graft (CABG) surgery is a major problem and may cause perioperative and late failure of bypass conduits. Increased oxidative stress plays important roles in myocardial and vascular dysfunction in patients undergoing CABG [4]. Hydrogen peroxide (H2O2) is an important derivative of oxidative metabolism and is a major contributor in oxidative stress-induced functional and metabolic dysfunction [5]. H2O2 is already used as an experimental model for oxidative stress and it has been shown to induce concentration dependent increases in contraction in various blood vessels including saphenous veins [7,8] and potentiates the effects of vasoconstrictor agents [9]
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