| Background:percutaneous coronary intervention(PCI)is frequently associated with the potential ischemic-reperfusion injury. Especially,ventricular tachyarrhythmias,including ventricular tachycardia(VT)and ventricular fibrillation(VF),induced by coronary artery occlusion/reperfusion,are the major direct causes of sudden cardiac death in patients with coronary artery disease,and sudden cardiac death is a leading cause in increasing cardiovascular mortality. It is not very clear regarding the mechanism and prevention of reperfusion arrhythmia. Hydroxymethylutary coenzyme A reductase inhibitors(statins) have shown to have effects independent of their cholesterol- lowering effects,referred to as pleiotropic effects including improving the funtion of vascular endothelial,stabilize and reverse the atherosclerotic plaque and so on. It has been shown that pretreatment with statin is effective in preventing reperfu- sion arrhythmia after ischemiac-reperfusion in the experimental model and clinical study. Therefore,it is important to investigate possible anti-arrhythmic effects of statins,but its electrophysiological mechanism is unclear. Ezetimibe regulates lipids mainly, besiedes improvement endothelial funtion,anti-inflammatory and antioxidant. In this study,we used the whole cell patch clamp recording techniques to study the effects of ezetimibe and simvastatin for L-type calcium channel current(ICa-L)which distribute rat right ventricular myocytes.Objective:This study aims to observe the effects of simvastatin and ezetimibe on L-type calcium channel in rat right ventricular myocyte, explore the mechanism of ion channels that simvastatin inhibit ischemia reperfusion arrhythmia and have a preliminary understanding that wether ezetimibe can prevent ischemia reperfusion arrhythmia.Methods:75 healthy rats were randomly diveded into control group, ischemia reperfusion group, ezetimibe(5mg/kg/d for two week) group,simvastatin(20mg/kg /d)for two weeksgroup, ezetimibe/simvastatin(ezetimibe 5mg/kg/d and simvastatin 10mg/kg/d) for two weeks group. Single mycocytes were isolated from right ventricular of rat with collagenase II, the control group means that ionic currents were recorded after 8min of perfusion with physiological desktop solution;ischemia reperfusion group, ezetimibe group,simvastatin group, ezetimibe/simvastatin group mean that ionic currents were recorded in one hour after 8min of physiological desktop,then 15 min of ischemia hypoxia liquid,at last 8min of physiological desktop.Results: Peak ICa-L current density(at 10mv) was significantly different in the hyperpalarizing direction in ischemia reperfusion group(-2.5128±0.703 p A/p F,n=14) compared with control group(5.0174±1.345 p A/p F,n=12, P<0.05), simvastatin group(-3.9105±0.891 p A/p F, n=14,P<0.05) and ezetimibe/simvastatin group(-3.6625± 0.901 p A/ p F, n=19, P<0.05).While it was no significantly different in ezetimibe group(-3.0717 ±1.312 p A/p F,n= 11) compared with ischemia reperfusion group( P>0.05); Half maximun inactivation voltage was significant different in in ischemia reperfusion group(-31.022±6.295 mv,n=11) compared with control group(-23.931±3.099,n=11,P<0.05), simvastatin group(-24.876±5.489, n=8,P<0.05),ezetimibe/simvastatin group(-26.242±3.253,n=10,P<0.05), while it was no significantly different in ezetimibe group(-32.786±2.1847,n= 9) compared with ischemia reperfusion group( P>0.05); Inactivation and recovery time constants was significant different in in ischemia reperfusion group(708.806±193.010 ms,n=15) compared with control group(527.151±139.639 ms,n=18,P<0.05), ezetimibe group(542.038±140.014 ms, n=13, P<0.05),simvastatin group(548.740±160.817 ms,n=13,P<0.05), ezetimibe/simvastatin group(485.576±140.74 ms, n=11,P<0.05).Conclusion:It is indicated that ischemia reperfusion induces significant reduction in ICa-L,accelerate ICa-L inactivation and prolong the recovery after inactivation. Pretreatment with simvastatin can improve the situation. Pretreatment with ezetimibe can only shorten recovery time after ischemia/reperfusion, have no effect on ICa-L and ICa-L inactivation. |
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