Effects Of Ezetimibe And Simvastatin On Transient Outward Potassium Current In Ischemia-reperfused Ventricular Myocytes In Rats

Objective To observe the impact of alone or combined use of Ezetimibe and Simvastatin on transient outward potassium current( Ito) in ventricular myocytes of rats suffering from simulated ischemia and reperfusion(IR). Methods Seventy-five male rats were randomly divided into 5 groups, control group(CON), control-IR group(CIR), ezetimibe treatment group(EIR), simvastatin treatment group(SIR) and combined ezetimibe and simvastatin treatment group(ESIR). After 2 weeks of treatment with intragastic normal saline or drugs(ezetimibe or simvastatin or combined), single myocytes were isolated from right ventricular with collagenase Ⅱ and It o were recorded by whole-cell patch clamp technique(Hearts of CON group were perfused with the Tyrode’s solution while those of other groups were perfused with IR solution). Results(1) The Ito current density at +60mV was significantly lower in CIR group(15.29±3.59 p A/pF) than CON group(26.45±4.70pA/pF),(P<0.001), it was higher in SIR group(21.83±2.20 p A/pF) and ESIR group(20.90±3.34 pA/pF), while there was no differences between EIR(15.63±1.46 pA/pF) and CIR group, between SIR and ESIR group, respectively(P>0.05).(2) There were significant differences on the half- inactivation(V1/2) between CON(-47.45±2.18 mV, n=9) and CIR group(-57.81±2.20 mV, n=11),(P<0.05), SIR(-46.93±2.05 mV, n=12) and CIR group(P<0.05), as well as ESIR(-51.73±1.21 mV, n=11) and CIR group(P<0.05), while there were no significant differences between SIR and ESIR group, between EIR(-54.31±2.53 mV, n=12) and CIR group, respectively(P>0.05). There were no significant differences on the slope factors among the five groups(P>0.05).(3) The time-constant(τ) of Ito recovery curves from inactivation was significantly longer in CIR group(51.14±1.72 ms, n=7) than CON group(25.10±2.56 ms, n=7),(P<0.05), it was shorter in SIR group(30.29±3.29 ms, n=7) and ESIR group(31.59±2.01 ms, n=7) than CIR group,(P<0.05), while there was no differences between EIR(47.29 ± 2.23 ms, n=7) and CIR group, SIR and ESIR group, respectively,(P>0.05). Conclusion(1) As ventricular myocytes in rats underwent simulated IR, the peak Ito current density was down-regulated, the steady-state inactivation curves were moved to the left, and Ito recovery time from inactivation was prolonged.(2) Ezetimibe and simvastatin combined treatment or double dose of simvastatin could ameliorate the changes, as ezetimibe could not.(3) Combining ezetimibe with statin may provide similar beneficial effects on myocardial ion channel as double dose of statin.