心房颤动犬心房肌肾素-血管紧张素系统改变

Changes of atrial renin-angiotensin system in atrial fibrillation dogs induced by chronic rapid atrial pacing

目的探讨慢性心房快速起搏诱发心房颤动(房颤)犬心房肌肾素血管紧张素系统(RAS)的改变。方法13只犬随机分为假手术组(n=6)和起搏组(n=7)。起搏组犬无菌开胸后在右心房缝植5对心外膜记录电极,电极尾端经皮下由犬背部穿出;在右心耳缝植螺旋型起搏电极,连接实验用AOO高频起搏器(400次/min),心房快速起搏6周,建立房颤犬模型;假手术组犬仅缝植心外膜记录电极和起搏电极而不起搏。经心外膜电极记录各组犬房颤诱发情况;采用放射免疫方法检测两组犬左心房及右心房组织血管紧张素Ⅰ(AngⅠ)、血管紧张素Ⅱ(AngⅡ)含量及肾素活性;采用逆转录聚合酶链反应(RTPCR)检测两组犬心房肌肾素、血管紧张素原和血管紧张素转换酶mRNA表达水平改变。结果(1)起搏组7只犬均经短阵快速刺激(burstpacing)诱发出房颤,房颤诱发率和平均持续时间较假手术组显著增加(P<0.01);(2)起搏组犬心房肌AngⅠ、AngⅡ含量较假手术组犬心房肌明显升高(P<0.01),肾素活性亦显著增加(P<0.01);同一组犬左心房与右心房组织AngⅠ、AngⅡ含量及肾素活性差异无统计学意义(P>0.05);(3)起搏组犬心房肌肾素、血管紧张素原和血管紧张素转换酶mRNA表达较假手术组犬心房肌显著上调(P<0.01)。结论慢性心房快速起搏诱发房颤犬心房肌AngⅠ、AngⅡ含量及肾素活性显著增加,可能是局部RAS基因表达上调的结果,提示房颤伴随心房肌RAS激活。

Objective To investigate the changes of atrial renin-angiotensin system (RAS) in atrial fibrillation (AF) dogs induced by chronic rapid atrial pacing. Methods Thirteen dogs were randomly divided into sham-operated group (n=6) and pacing group (n=7). Five pairs electrodes were sutured to right atrium. A pacemaker (AOO) was implanted in a subcutaneous pocket and attached to a screw-in epicardial lead in the right atrial appendage. The dogs in pacing group were paced at 400 bpm for 6 weeks. Pacemakers in sham-operated group dogs were not actived. The inducibility and duration of AF were measured in both groups. The angiotensin Ⅰ(AngⅠ), angiotensinⅡ(AngⅡ)levels and renin activity in atrial myocardium were measured by radioimmunological method. The expression of atrial renin, angiotensinogen and angiotensin converting enzyme (ACE) mRNA were semi-quantified by reverse transcription-polymerase chain reaction. Results(1) AF was readily inducible by burst pacing in 7 dogs after 6 weeks pacing. The inducibility and duration of AF in pacing group were significantly larger than those in sham-operated group (P<0.01);(2) Atrial AngⅠ, AngⅡ levels and renin activity were elevated significantly in pacing group than those in sham-operated group (P<0.01). But there was no difference between right and left atrium in the same group.(P>0.05); (3) Up-regulation of atrial renin, angiotensinogen and ACE mRNA were found in pacing group (P<0.01). Conclusion Being the result of RAS mRNA up-regulation, atrial AngⅠ, AngⅡ levels and renin activity show a remarkable increase in atrial fibrillation dogs, indicating that atrial fibrillation is correlated with the activation of local RAS.