Mitochondrial dysfunction and redox signaling in atrial tachy...( Researchers at the University Hospit...)

Researchers at the University Hospital of Magdeburg (Germany) have discovered that atrial tachycardia is associated with mitochondrial dysfunction and oxidative stress followed by the activation of the NF-kB signalling pathway with induction of NF-kB target gene expression in atrial tissue. Their study will appear in the May 08 issue of Experimental Biology and Medicine. Multiple tachycardia-associated factors appear to contribute to this response, which all are directly or indirectly linked to oxidative stress. Accordingly, blockade of the angiotensin II type 1 receptor, inhibition of L-type calcium channels, inhibition of NADPH oxidase, applications of antioxidants, and inhibition of NF-B activation were all found to abolish or decrease the tachycardia-dependent changes in the atrial tissue.

The interdisciplinary research team, led by Uwe Lendeckel, a professor of Experimental Internal Medicine and Andreas Goette, Deputy Chief of Cardiology, designed the study to determine the influence of tachyarrhythmia on endocardial dysfunction (called endocardial remodelling) and to decipher the molecular mechanism(s) that translate pathologically increased heart rates into myocardial/endocardial dysfunction. Endocardial dysfunction appears as a well recognised risk factor for thromboembolic events in patients with atrial fibrillation (AF). Therefore, the underlying pathophysiology of endocardial remodelling is of clinical importance.

The facts that equal results were observed in ex vivo atrial tissue from patients with AF and in ex vivo rapidly paced tissue samples from patients with sinus rhythm (SR), together with the observation that verapamil most potently prevented oxidative stress and associated signalling pathway activation, led us to conclude that the elevated frequency per se and concomitant Ca2+-overload precede and induce mitochondrial dysfunction and oxidative stress in AF said Lendeckel. Goette added Our results have several clinic
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