Taxol, a microtubule stabilizer, prevents atrial fibrillation in in vitro atrial fibrillation models using rabbit hearts.
BACKGROUND
Increased atrial oxidative stress plays an important role in the pathogenesis of atrial fibrillation. A predisposition for atrial fibrillation can be produced by altering the activities of enzymes related to reactive oxygen species metabolism. Microtubule integrity is necessary for cardio-protection; microtubules are involved in many cellular processes, including enzymatic activity. Taxol, a common microtubule stabilizer, can protect cardiac myocytes from oxidative stress. However, its effects on atrial fibrillation remain unknown.


METHODS
In vitro rabbit heart models of ischemia-, stretch-, and cholinergic agitation-induced atrial fibrillation were developed. Using either a fluorometric or spectrophotometric assay, we measured reactive oxygen species and the activities of oxidative enzymes including nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, xanthine oxidase, mitochondrial electron transport chain complexes I, mitochondrial electron transport chain complexes III, and superoxide dismutase.


RESULTS
Taxol effectively reduced the incidence of ischemia-, stretch- and cholinergic agitation-induced atrial fibrillation in in vitro rabbit heart models by 50%, 60%, and 40%. Moreover, Taxol decreased the level of reactive oxygen species by 46%, 49%, and 70% in ischemia-, stretch- and cholinergic agitation-induced atrial fibrillation models. Additionally, the activities of NADPH oxidase and xanthine oxidase were increased, whereas those of mitochondrial electron transport chain complexes I and III and superoxide dismutase were not affected.


CONCLUSIONS
Taxol, a microtubule stabilizer, prevents atrial fibrillation in in vitro atrial fibrillation model using rabbit hearts. This stabilizer most likely prevents atrial fibrillation by reducing the level of reactive oxygen species.
Xiao
Junjie
J
Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai, China.
Zhang
Hong
H
Liang
Dandan
D
Liu
Ying
Y
Liu
Yi
Y
Zhao
Hong
H
Li
Jun
J
Peng
Luying
L
Chen
Yi-Han
YH
D000818:Animals; D001281:Atrial Fibrillation / Q000517:prevention & control*; D002316:Cardiotonic Agents / Q000494:pharmacology; D018678:Cholinergic Agents / Q000494:pharmacology; D042967:Electron Transport Complex I / Q000378:metabolism; D014450:Electron Transport Complex III / Q000378:metabolism; D006325:Heart Atria / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008870:Microtubules / Q000378:metabolism; D023421:Models, Animal; D032383:Myocytes, Cardiac / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress; D017239:Paclitaxel / Q000494:pharmacology*; D011817:Rabbits; D011897:Random Allocation; D017382:Reactive Oxygen Species / Q000378:metabolism; D013314:Stress, Mechanical; D013482:Superoxide Dismutase / Q000378:metabolism; D050257:Tubulin Modulators / Q000494:pharmacology*; D014969:Xanthine Oxidase / Q000378:metabolism
D002316:Cardiotonic Agents; D018678:Cholinergic Agents; D017382:Reactive Oxygen Species; D050257:Tubulin Modulators; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D019255:NADPH Oxidases; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III; D017239:Paclitaxel