Effects Of Oxidative Stress On Electrophysiology In Human Atrial Myocytes

IntroductionAtrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice, while its prevalence is continuously increasing during the past few decades mainly due to aging of the population and improved survival of patients with other cardiovascular diseases. Since AF is independently associated with increased cardiovascular morbidity and mortality, it unequivocally represents a major public health problem. Almost one century has been elapsed since the first electrocardiographic recognition of the arrhythmia, but we are still far from an effective cure. Even though the pathophysiology of AF has been extensively studied during this period, it remains incompletely understood.Despite these considerations, recent advances in this field reinforce thenotion that improved understanding of the underlying mechanisms will lead to more specific and effective treatments. It has long been known that AF has a propensity to become sustained over time. Compelling evidence is accumulating that AF development and perpetuation depends on the electrophysiological and structural substrate of the atria. The structural substrate refers to abnormalities in atrial architecture such as atrial dilatation,fibrosis, apoptotic phenomena, tissue dedifferentiation and others. On the other hand, the electrophysiological substrate refers mainly to changes such as effective refractory period (ERP) shortening, loss of rate adaptation of the refractory period, prolongation of conduction, and increased dispersion of refractoriness and conduction. In their seminal study, Wijffels et al. were the first to demonstrate in experimental animals that AF provokes structural and functional alterations in atria that favour perpetuation of the arrhythmia. The underlying pathophysiological mechanism was named 'remodeling' indicating the development of the electrophysiological and structural substrate that promotes the maintenance and reoccurrence of AF. During the past few years, the role of novel pathophysiologic pathways that involve inflammatory and oxidative processes is under meticulous investigation.Interestingly, recent studies have demonstrated the implication of oxidative stress within the atrial tissue during AF suggesting a potential role in the remodeling phenomenon. Also, several pharmacologic approaches with non-channel-blocking drugs that have antioxidant and anti-inflammatory properties show beneficial effects on AF development. Since the publication of the first brief review regarding these issues. The purpose of the study was to investigate effects of oxidative stress on electrical remodeling in human atrial myocytes.Materials and methodMaterials1. specimens:single human atrial myocytes2. Reagents for pacth-clampMethod1. isolation of single human atrial myocytes by method of enzyme digestion2. normal and AF groups respectively consist of control, H₂O₂ and Vc group,different intervene to different group in bath solution3. whole-cell pacth-clamp recordingResultsH₂O₂ has both sides of effect on I_kur and I_Ca,L depanding on its concentration.The currunt dentities of I_kur and I_Ca,L significantly increase at low concentration(＜1μM),decrease at high concentration. Action potential duration decrease be normal-decrease with the increasing of H₂O₂ concentration. Antioxidant Vc can reverse these changes induced by H₂O₂. Conclusion1. oxidative stress can affect action potential duration in human atrial myocytes,increasing susceptivity of atrial fibrillation.2. antioxidant can reverse the acute change induced by oxidant,but can not affect "electrical remodeling" in AF.