[AF-FORUM] 168E ACEI和ARB在房颤中的应用 Dr. Savelieva

[AF Symposium]

大家好！
已有令人信服的试验证实了RAAS抑制剂血流动力学效 
应之外的阻断心房重构作用。AF造成的心房扩大与AF 
增加了血管紧张素Ⅱ在局部组织的合成有关。心房中 
血管紧张素Ⅱ受体的密度往往比心室高，使心房更容 
易受到血管紧张素的影响。随后，一系列磷酸化过程 
刺激血管紧张素Ⅰ型受体，进而激活丝裂原活化的蛋 
白激酶（MAP），MAP激酶反过来使心肌细胞肥大，成纤 
维细胞增殖，胶原蛋白聚积和凋亡。而且，血管紧张 
素Ⅱ通过对离子通道的间接作用改变心房的电生理特 
性，还可以通过影响缝隙连接破坏细胞间的偶联。 
RAAS抑制剂其它可能的作用机制还包括抗交感、抗炎 
症和抗血小板的作用。
RAAS抑制剂对于AF的抗心律失常作用陆续有喜人结果传 
出。然而，尽管许多回顾性的分析、小型的前瞻性研 
究和荟萃分析，以临床实验（例如2005年的Healey等） 
为基础，显示了RAAS抑制剂抗心律失常的潜在作用， 
但这些前瞻性研究的结果缺乏一致性。回顾性分析中 
提及的结果未能在前瞻性研究中证实，例如在CHARM研 
究中，AF是一个特别的预设终点，而CAPRAF研究中终点 
则是患者的电复律。还有一些临床研究是关于现在使 
用的所有ARB，例如GISSI-AF，补充的ACTIVE-AF和ANTIPAF研究 
等等，这些都是以AF作为主要重点的。

I Savelieva
St George's Hospital, London


168E ACE inhibitors and ARBs in AF. Dr. Savelieva

Hi
There is very impressive experimental evidence of the effects of RAAS  
blockade on atrial remodeling beyond its haemodynamic effects. Atrial  
stretch associated with AF increases local synthesis of angiotensin  
II. The density of angiotensin II receptors in the atria is generally  
greater than in the ventricles, making the atria more vulnerable to  
the effects of angiotensin. Subsequently, stimulation of angiotensin  
type 1 receptors, via a number of phosphorylation processes, results
in activation of mitogen-activated protein kinases. MAP kinases, in  
turn, promote myocyte hypertrophy, fibroblast proliferation,  
accumulation of collagen, and apoptosis. In addition, angiotensin II  
modifies atrial electrophysiology by indirect effects on ion channels  
and may also impair cell-to-cell coupling associated with gap  
junction remodeling. Other possible mechanisms of RAAS inhibitors  
include anti-sympathetic and anti-inflammatory effects as well as  
antiplatelet action.
There is much excitement going on about the antiarrhythmic effects of  
RAAS inhibitors in AF. However, although retrospective analyses,  
small prospective studies, and meta-analyses, based on these studies  
(e.g., Healey et al, 2005), demonstrated the antiarrhythmic potential  
of RAAS blockade, the findings in prospective trials appear less  
consistent. The reports based on the retrospective analyses, were not  
convincingly reproduced in the prospective studies, such as in the  
CHARM trials, in which AF was a pre-specified end-point, or the  
CAPRAF study of cardioverted patients. There are several on-going  
trials with virtually every existing ARB, such as GISSI-AF, ancillary  
ACTIVE-AF, and ANTIPAF studies, which focus on AF as their primary  
end-point.

I Savelieva
St George's Hospital, London
徐怡琼译 王玲洁校


--
Dr. Sergio Dubner
President of Scientific Committee

Dr. Edgardo Schapachnik
President of Steering Committee