犬心房颤动时T型钙通道在心房电重塑中的作用及机制探讨  

T-type calcium channel effects on atrial electrical remodelling and an approach to its mechanisms during atrial fibrillation

作　　者：刘元生[1] 郭继鸿[1] 张海澄[1] 李学斌[1] 许原[1] 张幼贻 袁兰[3] 

机构地区：[1]北京大学人民医院心内科,北京100044 [2]北京大学第三医院血管研究所,北京100083 [3]北京大学医学部激光共聚焦显微镜室,北京100083

出　　处：《中国实用内科杂志》2007年第12期929-931,共3页Chinese Journal of Practical Internal Medicine

基　　金：国家自然科学基金;北京大学985项目(30271431);北京市自然科学基金(7032030)

摘　　要：目的探讨犬心房颤动（房颤）时T型钙通道在心房电重塑中的作用及机制。方法将2002年2月至2006年10月北京大学人民医院动物实验的杂种犬15条，分为3组，每组5条，分别为正常对照组、单纯房颤组和房颤＋mibefradil组。房颤组在右心房植入起搏器进行快速起搏建立犬慢性房颤模型；房颤＋T型钙通道阻滞剂mibefradil组在起搏术后第2天开始给mibefradil（术后稳定24h）。正常对照组不植入起搏器。采用电生理检查方法测定房颤的持续时间和心房有效不应期；胶原酶Ⅱ型分离心房肌细胞，激光共聚焦显微镜检测Ca^2＋通道阻滞剂对细胞内Ca^2＋浓度变化的影响。结果（1）术前的心房有效不应期为280／90～110ms。起搏24周时，房颤＋mibefradil组的心房有效不应期延长为2000／1400～1700ms。，起搏24周时单纯房颤组中有75％的犬呈自身持续性房颤，而房颤＋mibefradil组有20％呈持续性房颤，其余犬在给予短阵猝发刺激（500／min）时可诱发出房颤，持续时间为1～6min。（2）正常对照组的心房肌细胞在阻滞L型ca“通道后细胞内Ca“浓度没有明显改变（1．17±0、09OD比值），单纯房颤组在阻滞L型Ca^2＋通道后细胞内Ca^2＋浓度明显升高（2．35±1．05OD比值），与正常对照组比较差异有显著性意义（P〈0．05），而房颤＋mibefradil组在阻滞L型Ca^2＋通道后细胞内Ca“浓度比单纯房颤组下降30％（2．05±0.90OD比值）。（3）正常对照组、单纯心房颤动组和房颤＋mibefradil组的心房肌细胞在阻滞T型Ca^2＋通道后细胞内Ca^2＋浓度均增高（1．49±0.17，1．53±0．33和1．38±0.35OD比值），且3组间比较差异均无显著性意义。结论（1）T型Ca^2＋通道阻滞剂能够明显延长房颤时的心房有效不应期，并能缩短房颤的持续时间，但并不能阻止房颤的发生；（2）房颤时心房肌细胞的T型Ca^2＋电流增加，而LObjective To inquire into T-type calcium channel effects on atrial electrical remodelling and its mechanisms during atrial fibrillation. Methods Animal experiment was performed in Peking University Pepole＇s Hospital from Feb. 2002 to Oct. 2006. Fifteen adult cross-bred clogs were used in the experiment. Ten dogs underwent continuous rapid atrial pacing（500 beats/min）for twenty-four weeks to create persistent atrial fibrillation. In five rapidly-paced dogs,50mg pure powder/day of mibefradil dihydroehloride was given from the second day after pacemaker implantation and continued until the twenty-fourth week. A group of size-matched dogs（n =5 ）without being given mibefradil was used as a pure atrial fibrillation group. Another group of size-matched dogs（ n = 5 ）without pacemaker implantation was used as a control group. Atrial fibrillation duration was determined by electrophysiological study. Canine atrial myocytes were isolated by enzymaticdissociation and intracellular Ca^2＋ cytosolic transient was studied with confocal imaging. Results （ 1 ） The preoperation atrial effective refractory period was 280/90 - 110 ms. In the twenty-fourth week after rapid atrial pacing, atrial effective refractory period was obviously extended（2000/1400- 1700 ms） in the T-type Ca^2＋ channel blocker group compared with the preoperation one. In the twenty-fourth week, the induced rate of persistent atrial fibrillation was 75% in atrial fibrillation group, whereas the persistent atrial fibrillation occurred in only one case（20% ）in the T-type Ca^2＋ channel blocker group. （2）Intracellular Ca^2＋ concentration of atrial myocytes was unremarkably changed in control group after blocking L-type Ca^2＋ channel（ 1.17 ± 0. 09 OD ratio）, whereas the intracellular Ca^2＋ concentration was obviously enhanced（2. 35 ± 1.05 OD ratio） （P 〈 0. 05）in atrial fibrillation group compared with that of control group, and the Ca^2＋ concentration in the T-type Ca^2＋ channel blocker group was reduced by

关 键 词：心房颤动 心房电重塑 钙通道 

分 类 号：R5[医药卫生—内科学]