Rapid pacing of human atrial tissue induced oxidative stress and mitochondrial dysfunction, which was effectively prevented by calcium channel blockade with verapamil.
Calcium inward current via L-type calcium channels contributes to oxidative stress and increased expression of adhesion molecules during atrial tachyarrhythmia, which can be mitigated by calcium channel blockade or antioxidants.
Accumulating evidence links calcium-overload and oxidative stress to atrial remodeling during atrial fibrillation (AF). Furthermore, atrial remodeling appears to increase atrial thrombogeneity, characterized by increased expression of adhesion molecules. The aim of this study was to assess mitochondrial dysfunction and oxidative stress-activated signal transduction (nuclear factor-kappaB NF-kappa B, lectin-like oxidized low-density lipoprotein receptor LOX-1, intercellular adhesion molecule-1 ICAM-1, and hemeoxgenase-1 HO-1) in atrial tissue during AF. Ex vivo atrial tissue from patients with and without AF and, additionally, rapid pacing of human atrial tissue slices were used to study mitochondrial structure by electron microscopy and mitochondrial respiration. Furthermore, quantitative reverse transcription polymerase chain reaction (RT-PCR), immunoblot analyses, gel-shift assays, and enzyme-linked immunosorbent assay (ELISA) were applied to measure nuclear amounts of NF-kappa B target gene expression. Using ex vivo atrial tissue samples from patients with AF we demonstrated oxidative stress and impaired mitochondrial structure and respiration, which was accompanied by nuclear accumulation of NF-kappa B and elevated expression levels of the adhesion molecule ICAM-1 and the oxidative stress-induced markers HO-1 and LOX-1. All these changes were reproduced by rapid pacing for 24 hours of human atrial tissue slices. Furthermore, the blockade of calcium inward current with verapamil effectively prevented both the mitochondrial changes and the activation of NF-kappa B signaling and target gene expression. The latter appeared also diminished by the antioxidants apocynin and resveratrol (an inhibitor of NF-kappa B), or the angiotensin II receptor type 1 antagonist, olmesartan. This study demonstrates that calcium inward current via L-type calcium channels contributes to oxidative stress and increased expression of oxidative stress markers and adhesion molecules during cardiac tachyarrhythmia.
Bukowska et al. (Thu,) conducted a other in Atrial fibrillation. Rapid pacing and calcium channel blockade vs. Unpaced tissue / patients without AF was evaluated on Mitochondrial structure, respiration, and expression of oxidative stress markers and adhesion molecules. Rapid pacing of human atrial tissue induced oxidative stress and mitochondrial dysfunction, which was effectively prevented by calcium channel blockade with verapamil.