< International Circulation>: What do you suspect to be the mechanism responsible for these effects regarding RAS blockade’s effect on atrial fibrillation?

    Prof. Schneider:  I think it is a combination of things.  There are hemodynamic effects.  These drugs have a very beneficial hemodynamic profile.  They inhibit fibrosis and may have some direct effects ion channels.  In terms of the hemodynamic effects， we know from studies like the CAFÉ study， a being a subanalysis of the ESCOTT study， where they looked at the effects of an ACE inhibitor such as propindoprel versus other beta-blockers， and you could see that RAS blockade was able to lower blood pressure to the same degree in the brachial artery but the central blood pressure wasn’t lowered as much with beta blockade as with RAS blockade.  One of the reasons is that with these drugs you have a good lowering of central blood pressure and that reduces the strain on the heart.  So hemodynamics are very important， but also we know that angiotensin II can cause fibrosis.  This then is another way of preventing atrial fibrillation.  Thirdly， there is some evidence that these drugs have effects on ion channels， for example delayed rectifier channels or calcium channels that have something to do with atrial fibrillation.  These channels seem to be involved with atrial fibrillation.  It might be that they also have some direct anti-arrhythmic properties but the fact they the combination of amurdirone plus an ARB is beneficial suggests to me that it must be more than just the ion channels.  I think it is fibrosis and hemodynamics.