Effects Of 18β-Glycyrrhetinic Acid On Diastolic Function In Isolated Rat Hearts

Objective: To examine effects of different doses of 18β-glycyrrhetinic acid (18β-GA) on left ventricular end-diastolic pressure (LVEDP, mmHg), maximum rate of left ventricular pressure rise (+dP/dtmax, mm Hg/s), maximum rate of left ventricular pressure decline (-dP/dtmax, mm Hg/s) and coronary flow (CF, mL/min) of global ischemia-reperfusion isolated rat hearts pretreated by Anemonia sulcata Toxin II (ATX-II, 20nmol/L ) which was used to enhance the late sodium current (late INa) to increase the ischemia-reperfusion injury, and compare with the role of ranolazine (5μmol/L ) on them to investigate the effectiveness of 18β-GA on rat cardiac diastolic function.Methods: Isolated male Sprague Dawley (SD) rat hearts (n=80) were divided randomly into eight groups for Langendorff model: normal cardiac perfusion(A) group, ischemia-reperfusion(B)group, ischemia-reperfusion with ATX-II (C)group, ranolazine (D)group and 18β-GA (E) group, there were 10 hearts in each group. And E group was divided into 5μmol/L (E①) group, 10μmol/L (E②) group, 20μmol/L (E③) group and 40μmol/L (E④) group based on the concentrations of 18β-GA. LVEDP (mmHg), +dP/dtmax (mm Hg/s), -dP/dtmax(mm Hg/s) and CF(mL/min) were observed and recorded in the hearts. Results: (1) Compared to simple ischemia-reperfusion (B) group, 20μmol/L and 40μmol/L 18β-GA are able to improve range of LVEDP, +dP/dtmax, -dP/dtmax and CF changed from the baseline(%) to protect the diastolic function in ischemia-reperfusion rat hearts (P<0.05), and effects of 40μmol/L 18-GA is significant (P<0.01). Compared to ischemia-reperfusion hearts with ATX - II (C), all of 5μmol/L ranolazine, 5μmol/L 18β-GA, 10μmol/L 18β-GA, 20μmol/L 18β-GA, and 40μmol/L 18β-GA can improve cardiac diastolic dysfunction in rat hearts pretreated by ATX-II (P < 0.05). 20μmol/L and 40μmol/L 18β-GA can improve the diastolic dysfunction of ischemia-reperfusion isolated rat hearts pretreated by ATX-II, and the effect is similar to 5μmol/L ranolazine. (2)Improvement of 18β-Glycyrrhetinic acid on diastolic function in isolated rat hearts maybe dependent on concentration, 40μmol/L 18β-GA can effectively improve the diastolic dysfunction of in ischemia-reperfusion isolated rat heartsConclusion: 18β-glycyrrhetinic acid could improve diastolic dysfunction caused by ischemia-reperfusion in isolated rat hearts as ranolazine, and the mechanism of protective effect may be also similar to ranolazine that is inhibition of late sodium current (Late INa) in myocardial cells.