Amiodarone Prevent Electrophysiological Changes Of Acute Atrial Dilation Accompanied With Rapid Atrial Stimulation In Isolated Langendorff-perfused Rabbit Heart

ObjectiveElectrical remodeling are frequently observed under conditions that are associated with atrial dilation or atrial tachycardia, which are composed of atrial effective refractory period (AERP) abbreviation, loss of physiological rate adaptation, vulnerability of atrial fibrillation (AF) improvement. Incidence of the various atrial arrhythmia are strictly dependent on the changes of atrial refractory period. Decreases of atrial refractory period are divergent at different level of atrial pressures. By now, studies on alterations of conduction volecity still remain controversial. In clinical practice, atrial dilation is common in patients with AF, especially in left atrium. Usually atrial dilation is associated with atrial tachycardia. Atrial dilation and atrial tachycardia may play an important role in occurrence of paroxysmal and sustained atrial fibrillation. Amiodarone is an effective drug for a variety of arrhythmias in clinical practise, which has been reffered to as class III antiarrhythmic agent. The short-term and long-term electrophysiol effects of Amiodarone on cardiac cell are quite different. It prolongs both action potential duration and refractory period when adiministered long term, but blocks Na⁺ and Ca²⁺ channels after short-term administration. In the present study, we developed an isolated rabbit hearts experimental model, in which the right and left atrial pressures could be varied over a wide range of values, the direct effects of acute and sustained biatrial dilatation followed with rapid electrical stimulation on the AERP, atrioventricular wenckebach cycle length (AVWCL), spatial dispersion of AERP, sequence and time of atrial activation weremeasured and the inducibility of AF by programmed electrical stimulation or Burst stimulation was observed. We studied the electrophysiological basis for AF treatment with amiodarone. Methods28 isolated Langendorff-perfused rabbit hearts was randomly divided into three groups: (1) acute atrial dilation group (n=9, atrial pressure 0% 6> 12 > 20 cmH20 respectively); (2) acute atrial dilation accompanied with rapid atrial stimulation group (add rapid atrial stimulation ten minutes at each level); (3) amiodarone group (Tyrode's solution with amiodarone 1.5mg/L). After a large atrial septum defect was created and the pulmonary artery was ligated, the superior caval vein and one of the pulmonary veins were cannulated to measure the pressures of right and left atrium respectively. The inferior caval vein was cannulated to serve as the exclusive outflow tract for the coronary perfusion. By changing the height of this cannula, the pressure in the biatrium could be easily controlled. Then S1S2 stimulation and Burst were used to evaluate the vulnerability to AF as well as the measurements of AERP, AVWCL and other parameters of electrophysiology. ResultsFollowing the intra-atrial pressure increased from 0 C111H2O to 20 cmHbO, AERP were decreased (73.11 ± 12.85ms vs 48.00± 12.04ms in LLA, 79.78± 19.56ms vs 42.67 ± 13.68ms in LRA), showing a high correlation with the increase of atrial pressure (LLA r=-0.489, LRA r=-0.565). Spatial dispersion of AERP hadn't obvious changes (26.44+12.74ms vs 20.44+ 11.22ms, p>0.05). Sequence of atrial activation had been changed, but the alteration of the individuality was divergent. The AVWCL, time of activation and sinus heart rate were increased, but there were no statistical singnificant differences. There was significant increase in vulnerability to AF and that was closely correlated to...