Biomedical Engineering Reference
In-Depth Information
and/or previous stroke (Hammwöhner
et al.
2007a). Depending on these risk
factors, the individual risk for thromboembolic events varies from about 2% to
18% per year.
Treatment of AF requires for optimized diagnostic and therapeutic management
taking into consideration individual patient characteristics and determinants of
clinical course and complications. AF therefore represents a signii cant health-
care burden. Total annual costs for treatment of AF were estimated at US $6.65
billion in the United States in 2005.
PATHOPHYSIOLOGY OF ATRIAL FIBRILLATION
Cardiac tachyarrhythmia is known to induce signii cant electrophysiological
and structural changes in cardiac tissue, which themselves may contribute to the
persistence and aggravation of AF (Goette
et al.
1996, Ausma
et al.
1997). h e
overall pathophysiological mechanism for electrophysiological changes in atrial
myocytes has been termed 'electrical remodeling. Besides substantial shortening
of the atrial action potential and alteration of other electrophysiological properties,
AF also causes signii cant structural changes ('structural remodeling') in atrial
tissue. Electrical and structural remodeling processes take place in atrial myocytes
as well as in atrial endocardial cells (the interior surface layer of both upper
heart chambers). In order to understand the impact of AF on adhesion molecule
expression, one needs to understand these remodeling processes and their impact
on downstream processes. Recent studies have provided initial insights into the
molecular mechanisms involved in the development of cellular and subcellular
changes. Altered intracellular calcium ion (Ca
2+
) homeostasis and angiotensin II
receptor type 1 (AT1R) activation have been identii ed as important remodeling
factors contributing to cellular and cardiac hypertrophy, atrial extracellular matrix
accumulation, and i brosis in AF (Goette
et al.
1996, Ausma
et al.
1997). Cellular
Ca
2+
-overloading on the one hand and AT1R-induced nicotinamide adenine
dinucleotide phosphate (NADPH) oxidase activity on the other hand have been
demonstrated to cause excessive intracellular oxidative stress. Oxidative stress
itself has also been identii ed to trigger atrial remodeling during AF ('positive
feedback loop'). Gene expression proi ling of atrial tissue samples from patients
with SR and AF revealed a decreased expression of antioxidative genes, whereas
expression of i ve reactive oxygen species (ROS)-producing genes was increased
(Kim
et al.
2005). At the molecular level, several AF-related alterations of atrial
tissue are due to activation of dif erent signal transduction systems. Recently, we
were able to show the impact of the nuclear factor kappa B (NF-κB) pathway in the
process of rapid pacing-induced oxidative stress (Bukowska
et al.
2008). NF-κB in
turn leads to upregulation of atrial adhesion molecule expression
(Fig. 2)
.
