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Inhibition of thrombin-induced platelet aggregation by levosimendan is modified by small changes in albumin concentration in vitro

This paper is available in a repository.
This paper is available in a repository.

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Abstract

OBJECTIVE: To investigate the effect of levosimendan and its modulation by albumin on thrombin-induced aggregation of isolated human platelets. METHODS: Platelet-rich plasma (PRP) and washed platelets (WPs) were obtained from venous blood of healthy volunteers and aggregation was measured turbidometrically. Protein-rich PRP and the protein-free WPs were incubated with levosimendan to obtain inhibitory concentration-response curves for the drug. Then PRP and WPs were pretreated with the inodilator drug in the absence and presence of human albumin. Aggregation was induced by 0.5 IU/mL to 1 IU/mL thrombin in PRP, and 0.1 IU/mL thrombin in WPs. RESULTS: Fifty per cent inhibitory concentrations (IC50) of levosimendan were calculated as 3 mu mol/L in PRP and 0.06 mu mol/L in WPs. In WPs, platelet inhibition induced by 0.06 mu mol/L of the drug was gradually decreased by small elevations of albumin concentrations (1.7 g/L to 5 g/L). In PRP, 5 g/L albumin also diminished the platelet inhibitory effect of the inodilator drug. CONCLUSION: Small changes in plasma albumin level modifies the inhibiton by levosimendan of thrombin-induced platelet aggregation in vitro. This finding could be partly related to the known protein binding of the inodilator drug and highlights the need of a careful adjustment of the dose of levosimendan in heart failure with concomittant hypoalbuminemia.