氯离子通道及其阻滞剂对家兔心肌缺血再灌注心律失常的影响
Effects of chloride ion channel and its blockers on myocardial ischemia reperfusion arrhythmias in rabbits
目的 探索氯离子通道及其阻滞剂DIDS、SITS和NPPB对心肌缺血再灌注所致心律失常的影响.方法 40只家兔分为对照组、缺血再灌注组、DIDS低剂量组、DIDS高剂量组、SITS低剂量组、SITS高剂量组、NPPB低剂量组和NPPB高剂量组,每组各5只,通过结扎后松扎冠状动脉前降支建立心肌缺血再灌注模型,实验过程中持续监测家兔标准肢体Ⅱ导联心电图,比较各组间家兔心率、心电图P波、R波、T波、ST段变化和心律失常评分.结果 缺血30 min时,与对照组比较,各组家兔均出现心率减慢[(199.8±4.0) ~ (253.6 ±2.1)比(267.0±3.4),均P<0.01],心电图出现P波[(0.216 ±0.019) ~ (0.356 ±0.024)比(0.186 ±0.019),均P<0.01]、R波[(0.564±0.017) ~(1.138±0.048)比(0.506 ±0.018),均P<0.01]和T波[(0.542 ±0.013)~(0.856 ±0.045)比(0.278±0.015),均P<0.01]增高及ST段[(0.326±0.027) ~ (0.668±0.054)比(0.024±0.023),均P<0.01]抬高,各组心律失常评分[(1.4±0.5) ~(4.6±0.5)比(0.4±0.5),均P<0.01]均显著增高;与缺血再灌注组比较,各干预组上述指标均显著改善[心率(214.8±3.4) ~ (246.8±4.0)比(199.8 ±4.0),均P<0.01;P波(0.216 ±0.019)~(0.316 ±0.011)比(0.356 ±0.024),均P<0.01;R波(0.564±0.017)~(0.980±0.035)比(1.138 ±0.048),均P<0.01;T波(0.542±0.013) ~(0.792±0.026)比(0.856 ±0.045),均P<0.01;ST段(0.326±0.027)~(0.596±0.018)比(0.668 ±0.054),均P<0.01;心律失常评分(1.4±0.5)~(3.8±0.4)比(4.6±0.5),均P<0.01],以DIDS组最优,其次为SITS组,再次为NPPB组,且高剂量亚组效果均优于低剂量亚组.再灌注60 min时,各组家兔心率均显著回升,心电图增高的P波、R波和T波及抬高的ST段逐渐回落,以DIDS组变化幅度最大,其次为SITS组,再次为NPPB组,且高剂量亚组效果均优于低剂量亚组,再灌注期心律失常评分比较亦有同样的趋势.结论 氯离子通道参与了心肌缺血再灌注心律失常的发生,在心肌缺血再灌注早期静脉予以氯离子通道阻滞剂DIDS、SITS和NPPB能够改善家兔心肌缺血及再灌注时的心电图表现并能够减轻再灌注心律失常的程度,其中以DIDS效果最好,其次为SITS,NPPB效果略差,且均以高剂量的效果较好.
更多Objective To explore the impact of chloride ion channel and its blockers 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS),cyanato-stilbene-2,2'-disulfonic acid (SITS) and 5-nitro-2-(3-phenyl-propylamino) benzoic acid (NPPB) on arrhythmias caused by myocardial ischemia reperfusion.Methods A total of 40 rabbits were divided into control,ischemia reperfusion,DIDS lowdose,DIDS high-dose,SITS low-dose,SITS high-dose,NPPB low-dose and NPPB high-dose groups.Myocardial ischemia reperfusion model was established by ligation of anterior descending coronary artery.And standard limb lead Ⅱ of electrocardiogram (ECG) was continuously monitored during the experimental process.Then comparisons of heart rate,ECG P wave,R wave,T wave,ST segment changes and arrhythmias score were made between the above groups.Results During 30-minute ischemia,compared with the control group,all other groups showed significantly decreased heart rate ((199.8 ±4.0)-(253.6 ± 2.1) vs (267.0 ±3.4),all P <0.0l),elevated ECG P wave ((0.216 ±0.019)-(0.356 ±0.024) vs (0.186±0.019),all P<0.01),Rwave ((0.564±0.017)-(1.138 ±0.048) vs (0.506±0.018),all P<0.01),T wave ((0.542 ±0.013)-(0.856 ±0.045) vs (0.278 ±0.015),all P <0.01) and ST segment ((0.326 ± 0.027)-(0.668 ± 0.054) vs (0.024 ± 0.023),all P < 0.01) and increased arrhythmia score ((1.4 ± 0.5)-(4.6 ± 0.5) vs (0.4 ± 0.5),all P < 0.01).Compared with the ischemia reperfusion group,the above indices significantly improved in the intervention groups (heart rate:(214.8 ± 3.4)-(246.8±4.0) vs (199.8±4.0),allP<0.01; Pwave:(0.216±0.019)-(0.316±0.011) vs (0.356 ±0.024),all P<0.01; R wave:(0.564 ±0.017)-(0.980 ±0.035) vs (1.138 ±0.048),all P < 0.01 ; T wave:(0.542 ± 0.013)-(0.792 ± 0.026) vs (0.856 ± 0.045),all P < 0.01 ; ST segment:(0.326 ±0.027)-(0.596 ±0.018) vs (0.668 ±0.054),all P <0.01 ; arrhythmia score:(1.4 ±0.5)-(3.8 ±0.4) vs (4.6 ±0.5),all P <0.01).Among which,the DIDS group was the best,followed by the SITS group and then the NPPB group.And the high-dose subgroups were better than those of the low-dose subgroups.During 60-minute reperfusion,the decreased heart rate upswung significantly in each group and the elevated P wave,R wave,T wave and ST segment fell back gradually.The DIDS group showed the most obvious amplitude change,followed by the SITS group and then the NPPB group.And the high-dose subgroups were better than those of the low-dose subgroups.The arrhythmia score during reperfusion showed the same trend.Conclusion Chloride ion channel is involved in the generation of myocardial ischemia reperfusion arrhythmia.Early application of chloride ion channel blockers DIDS,SITS and NPPB may improve the ECG manifestations and reduce the degree of reperfusion arrhythmia.
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