Atorvastatin treatment affects atrial ion currents and their tachycardia-induced remodeling in rabbits.
OBJECTIVE
Atrial fibrillation (AF) leads to electrical atrial remodeling including alterations of various ion channels early after arrhythmia onset. The beneficial effects of statins in AF treatment due to their influence on oxidative stress and inflammation are discussed. Our hypothesis was that statins might also alter atrial ion currents and their early tachycardia-induced remodeling.


METHODS
Effects of an atorvastatin treatment (7 days) on atrial ion currents and their tachycardia-induced alterations were studied in a rabbit model of tachycardia-induced electrical remodeling (rapid atrial pacing (600 min) for 24 and 120 h). Ion currents (L-type calcium channel [I(Ca,L)], transient outward current [I(to)]) were measured using whole cell patch clamp method and were compared with previous experiments in untreated but also tachypaced animals.


RESULTS
Atorvastatin treatment alone decreased I(Ca,L) similar to rapid atrial pacing alone, currents were also further reduced by additional atrial tachypacing. I(to) and its pacing-induced down-regulation after 24 h were not influenced by atorvastatin treatment. However, I(to) was still reduced after 120 h in atorvastatin-treated animals and did not return to control values as expected.


CONCLUSIONS
The present study establishes that an atorvastatin treatment can affect atrial ion currents and their tachycardia-induced remodeling in a rabbit model. These results show that-amongst other positive effects on oxidative stress and inflammation-the impact of statins on ion currents and their tachycardia-induced alterations might also play a role in "upstream" treatment of AF with HMG-CoA reductase inhibitors.
Laszlo
Roman
R
Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Eberhard Karls Universität Tuebingen, Tuebingen, Germany. roman.laszlo@gmx.de
Menzel
Karen Anna
KA
Bentz
Kerstin
K
Schreiner
Birgit
B
Kettering
Klaus
K
Eick
Christian
C
Schreieck
Juergen
J
D000818:Animals; D000069059:Atorvastatin; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D006325:Heart Atria / Q000187:drug effects / Q000503:physiopathology; D006538:Heptanoic Acids / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D011758:Pyrroles / Q000494:pharmacology*; D011817:Rabbits; D013610:Tachycardia / Q000188:drug therapy* / Q000503:physiopathology; D013997:Time Factors
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007473:Ion Channels; D011758:Pyrroles; D000069059:Atorvastatin