Biomedical Engineering Reference
In-Depth Information
were able to demonstrate elevated plasma concentrations of AngII in response
to rapid pacing
in vivo
. h ese i ndings are in line with studies that have already
shown a signii cant impact of the RAS system on the occurrence of AF (Goette
et al.
2000b). Previous experiments demonstrated that ACE inhibitors and ARBs
inl uence short-term atrial electrical alterations, which we coni rmed in our study.
h is ef ect, however, appears to decrease in the long term (Shinagawa
et al.
2002).
Besides the variable electrophysiological ef ects, ACE inhibitors and ARBs have
been clearly demonstrated to reduce the amount of pro-arrhythmic structural
alterations such as atrial i brosis. h e experimentally observed anti-arrhythmic
ef ects of ACE inhibitors and ARBs are supported by various retrospective analyses
of clinical trials (TRACE, ValHeFT, SOLVD, CHARM, LIFE).
Nevertheless, it still has to be proven whether the ef ect of ARBs observed in
our short-term
in vitro
and
in vivo
models corresponds to a clinically relevant
reduction of thromboembolic events in patients with AF. Interestingly, the
very i rst clinical results from the LIFE study already point in that direction. In
addition, further prospective clinical trials (ANTIPAF, ACTIVE-I, and CREATIV-
AF (Goette
et al.
2008b)) are being carried out to determine the impact of ARB
therapy on the occurrence of thromboembolic stroke during AF. h us, further
experiments in chronic AF models are warranted to elucidate the impact of ARB
in the long term on prothrombotic atrial alterations at the molecular level.
Recent analyses of the PROGRESS trial including more than 6,000 patients
showed that, in addition to the traditional risk factors, systemic levels of VCAM-1
provide prognostic information about recurrent ischemic stroke (Campbell
et al.
2006).
CONCLUSIONS
h e present studies provide evidence that AF and pacing-induced atrial tachycardia
increase the expression of adhesion molecules in the atrial endocardium within
hours. In addition, AF-induced expression of VCAM-1 is higher in the let atrium
than in the right atrium. h e prothrombogenic process of endocardial remodeling
can be substantially attenuated by ARB treatment, suggesting that angiotensin II
has a signii cant pathophysiological role in endocardial remodeling. However,
experiments in chronic AF models are warranted to determine the long-term
ei cacy of ARBs in this process.
SUMMARY
• AF and pacing-induced atrial tachycardia increase the concentration of
soluble serum adhesion molecules.
• AF and pacing-induced atrial tachycardia also increase expression of
membrane-bound adhesion molecules in the atrial endocardium and on
platelets. h ese processes occur rapidly within hours.
