快速心房起搏对家兔心房肌L型钙离子通道的影响及氯沙坦干预的研究

Effects of losartan on L-type calcium channel in rapid atrial pacing in rabbits

目的探讨以人工心脏起搏的方法制备家兔急性心房纤颤(atrial fibrillation,AF)模型时心房发生电重构的机制和干预方法。方法家兔45只随机分为生理盐水(NS)组、生理盐水起搏(NSP)组、氯沙坦起搏(LP)组。观测每组基础状态、快速心房起搏时心房有效不应期(AERP)及心房肌L-型钙通道的电流密度(ICa-L),并进行统计学处理。结果①快速起搏时NSP组较NS组各个基础周长下的AERP均显著下降(P<0.01);NSP组快速起搏6小时和8小时与NS组AERP的差距随着基础周长的下降而减少。②而快速起搏8小时后LP组AERP的下降较NSP组显著减轻(P<0.01);LP组快速起搏后与NS组AERP的差距随着基础周长的下降未见减少趋势。③NSP组较NS组心房肌ICa-L降低;LP组较NS组和NSP组心房肌ICa-L差异无统计学意义(P>0.05);而LP组较NSP组心房肌ICa-L的标准差显著降低(P<0.05)。结论快速心房起搏可引起AERP缩短及AERP频率适应性不良为特征的心房肌电重构。氯沙坦可以抑制这种电重构及心房肌ICa-L离散度增加,从而降低AF的发生。

Objective To investigate the electrical remodeling induced by rapid atrial pacing on rabbit model,by which the mechanisms of the electrical remodeling of atrial fibrillation（AF） may be analyzed. Additonally to investigate the effects of angiotensin receptor blocker losartan on atrial L-type calcium channel and to propose a new idea on clinical approach of AF. Methods A total of 45 healthy white rabbits no matter male or female were used in the study. The rabbits were randomly divided into three groups： normal saline （NS） group, NS pacing （NSP） group, losartan pacing （LP） group. The atrial effective refractory period（AERP） was measured by program stimulation, then the L-type Ca^2＋ current（ICa-L） of atrium cordis was measured. The data were delt with statistical analysis. Results （1）AERP at basic cycle lengths （BCL）from 200 to 150 ms was significantly shortened in NSP group compared with that of NS group （P 〈 0. 01） , after pacing for eight hours, AERP between NSP group and NS group was significantly shortened（ P 〈 0.01）. （2）After rapid atrial pacing for eight hours, AERP in LP group was significantly shortened than that of NSP group （P 〈 0.01）, but had no statistic significance as compared with that of NS group. With the descending of BCL, the equation of AERP between LP group and NS group was not shortened. （3） ICa-L of NSP group was significantly decreased as compared with that of NS group. ICa-L had no significant difference between LP group and NS group （ P〉0.05）. As compared with that of NSP group, ICa-L of LP group was not significantly descended,but the standard deviation of ICa-L was significantly descended （P 〈0.05）. Conclusion Atrial rapid pacing can induce the atrial electrical remodeling （AER） characterized shortening of AERP and the losing of physiological rate adaptation. Losartan can completely prevent not only AER but also the heightening of straggling tendency of ICa-L resulted in rapid atrial pacing thereby can depress the potential risk of AF.