脓毒症大鼠心房肌细胞部分心电改变及其对心房颤动易感性的影响

Electrical remodeling of atrial myocytes in septic rats and its effect on atrial fibrillation susceptibility

目的探讨脓毒症大鼠心房肌细胞心电改变及其对心房颤动(简称房颤)易感性的影响。方法 40只清洁级雄性SD大鼠随机分为假手术组和脓毒症组,每组20只,脓毒症组腹腔注射脂多糖诱导脓毒症模型,造模48 h后微电极肢体导联采集心电图,Labchart软件分析心率及P波延长时间。采用多微电极紧贴在大鼠左心房表面,利用50 Hz的6个Burst刺激进行房颤的诱发,Labchart软件记录心房外膜心电图及房颤诱发情况。急性分离心房肌细胞进行全细胞膜片钳,pClamp软件记录和分析大鼠心房肌细胞I_(Na)、I_(kur)电流密度、激活和失活动力学、失活后恢复情况。结果与假手术组相比,脓毒症组心率增快[(405.07±9.95)次/分vs (370.13±11.12)次/分,P<0.05],P波时限延长[(17.03±0.35)ms vs (14.04±0.46)ms,P<0.05],房颤发生率明显增加[66.7%vs 33.3%,P<0.05],I_(Na)电流密度显著降低[-60 mV时,(-219.76±13.24)pA/pF vs (-74.56±9.49)pA/pF,P<0.01],半数失活电压增大[(-99.88±13.24)mV vs (-74.56±9.49)mV,P<0.01],失活后恢复时间缩短[(9.28±0.82)msvs (16.09±0.97)ms,P<0.01],I_(kur)电流半数激活电压降低[(31.86±1.01) vs (47.06±3.67),P<0.01]。结论脓毒症大鼠房颤易感性明显增加,心肌细胞I_(Na)与I_(kur)电流密度及通道动力学的改变参与了脓毒症大鼠心房的心电改变。

Objective To investigate the electrocardiographic alterations in atrial myocytes of septic rats and their effect on susceptibility to atrial fibrillation(AF).Methods Forty clean grade male SD rats were randomly divided into sham-operated and sepsis groups,20 rats in each group.The sepsis group was injected intraperitoneally with lipopolysaccharide to induce sepsis model,and electrocardiograms were collected in microelectrode limb leads 48 hafter modeling,and Labchart software analyzed the heart rate and P-wave duration.Multi-microelectrodes were applied tightly to the left atrial surface of rats,and atrial fibrillation was induced using 50 Hz Burst stimulation,and Labchart software recorded the atrial epicardial electrocardiogram and AF induction.Acutely isolated atrial myocytes were subjected to whole-cell membrane clamp,and pClamp software recorded and analyzed INa,Ikurcurrent density,activation and inactivation kinetics,and recovery after inactivation in rat atrial myocytes.Results Compared with sham operation group,the heart rate increased[(405.07±9.95)bpm vs(370.13±11.12)bpm,P<0.05],and the duration of P wave prolonged[(17.03±0.35)ms vs(14.04±0.46)ms,P<0.05],the incidence of AF in septic group was significantly higher[66.7% vs 33.3%,P<0.05].The INacurrent density was significantly decreased[-60 mV,(-219.76±13.24)pA/pF vs(-74.56±9.49)pA/pF,P<0.01],and the inactivation voltage of half increased[(-99.88±13.24)mV vs(-74.56±9.49)mV,P <0.01],after deactivation,the recovery time shortened[(16.09±0.97)ms vs(9.28±0.82)ms,P<0.01]and the activation voltage of IKur current decreased by half[(47.06±3.67)vs(31.86±1.01),P<0.01].Conclusion The susceptibility to AF in septic rats is significantly increased.The changes of current density and channel dynamics of INaand Ikurin cardiomyocytes are involved in atrial electrical changes in septic rats.[Chinese Journal of Cardiac Pacing and Electrophysiology,2022,36(1):52-57]