RESUMEN
Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. It can occur at any age, however, it becomes extremely common in the elderly, with a prevalence approaching more than 20% in patients older than 85 years. AF is associated with a wide range of cardiac and extra-cardiac complications and thereby contributes significantly to morbidity and mortality. Present therapeutic approaches to AF have major limitations, which have inspired substantial efforts to improve our understanding of the mechanisms underlying AF, with the premise that improved knowledge will lead to innovative and improved therapeutic approaches. Our understanding of AF pathophysiology has advanced significantly over the past 10 to 15 years through an increased awareness of the role of "atrial remodeling". Any persistent change in atrial structure or function constitutes atrial remodeling. Both rapid ectopic firing and reentry can maintain AF. Atrial remodeling has the potential to increase the likelihood of ectopic or reentrant activity through a multitude of potential mechanisms. The present paper reviews the main novel results on atrial tachycardia-induced electrical, structural and contractile remodeling focusing on the underlying pathophysiological and molecular basis of their occurrence. Special attention is paid to novel strategies and targets with therapeutic significance for atrial fibrillation.
Asunto(s)
Antiarrítmicos/farmacología , Fibrilación Atrial/tratamiento farmacológico , Antiarrítmicos/química , Antiarrítmicos/uso terapéutico , Fibrilación Atrial/fisiopatología , Función Atrial/efectos de los fármacos , Atrios Cardíacos/fisiopatología , Humanos , Canales Iónicos/antagonistas & inhibidores , Canales Iónicos/metabolismoRESUMEN
AIM: In diabetes mellitus, several cardiac electrophysiological parameters are known to be affected. In rodent experimental diabetes models, changes in these parameters were reported, but only limited relevant information is available in other species, having cardiac electrophysiological properties more resembling the human, including the rabbit. The present study was designed to analyse the effects of experimental type 1 diabetes on ventricular repolarization and the underlying transmembrane potassium currents in rabbit hearts. METHODS: Diabetes was induced by a single injection of alloxan (145 mg kg(-1) i.v.). After the development of diabetes (3 weeks), electrophysiological studies were performed using whole cell voltage clamp and ECG measurements. RESULTS: The QT(c) interval in diabetic rabbits was moderately but statistically significantly longer than measured in the control animals (155 +/- 1.8 ms vs. 145 +/- 2.8 ms, respectively, n = 9-10, P < 0.05). This QT(c)-lengthening effect of diabetes was accompanied by a significant reduction in the density of the slow delayed rectifier K(+) current, I(Ks) (from 1.48 +/- 0.35 to 0.86 +/- 0.17 pA pF(-1) at +50 mV, n = 19-21, P < 0.05) without changes in current kinetics. No differences were observed either in the density or in the kinetics of the inward rectifier K(+) current (I(K1)), the rapid delayed rectifier K(+) current (I(Kr)), the transient outward current (I(to)) and the L-type calcium current (I(CaL)) between the control and alloxan-treated rabbits. CONCLUSION: It is concluded that type 1 diabetes mellitus, although only moderately, lengthens ventricular repolarization. Diabetes attenuates the repolarization reserve by decreasing the density of I(Ks) current, and thereby may enhance the risk of sudden cardiac death.