| ObjectiveRecent studies showed that activation of renin-angiotensin system (RAS) was involved in the development and maintenance of atrial fibrillation . It is accepted that intracellular calcium overload played an important role in the mechanism of electrical remodeling in the atraium. Moreover angiotensin â…¡ increases the intracellular calcium concentration and induces ventricular reperfusion arrhythmia. The greater density of AT1 receptor in atrial myocytes is observed. Thus, intracellular calcium overload induced by angiotensin II might play a role in atrial electrical remodeling. Angiotensin-(1-7) was found in recent years as a new number in RAS. Previous studies showed that the physiological action of angiotensin-(1-7) was opposite to angiotensin â…¡, it can protect myocytes and vascular endothelium cells and antagonize the active of angiotensin II in vivo and in vitro, it was thought as endogenous antagonist. The model of atrial rapid pacing in dogs was esteablished to investigate atrial effective refractory period (AERP), the rate adaptation of AERP, dispersion of AERP and the inducibility and duration of atrial fibrillation, and to observe the effects of angiotensin-(1-7) and angiotensin II on the atrial electrical remodeling. Method20 adult mongrel dogs of either sex, weight of ranging form 11 to 18 kg, were enrolled in this study. The dogs were anesthetized with 3% pentobarbital (30mg/kg), and then intubation and ventilation were given before thoractomy. Four pairs ofelectrode were sutured to four sites in the atrium (high right atrium HRA, low right atrium LRA, high left atrium HLA and low left atrium LLA). The surface electrocardiogram (lead II ,III,aVF), epicardiac electrogram, blood pressure and pH of arterial blood were continuously monitored and recorded during the experiment. High right atrium electrode was used as the pacing lead, and rapid pacing at 600 beats/min lasted 2 hours. The infusion of Ang-(l-7) (n=5), Ang II (n=5), Ang-(l-7) + AngII(n=5) was started 10 minutes before rapid pacing and maintained until the protocol was completed. The control group was given saline upto the end of the experiment. Rapid pacing was briefly paused every 30minutes for the first hour and therefore once one hour for the duration of pacing to allow for repeated assessment of AERP respectively at basic cycle length 200ms ^ 250ms n 350ms. Finally, measurements were made every 10 minutes after the cessation of pacing. ResultsIn the control group, the AERP of three sites was significantly shortened (p<0.01) during rapid atrial pacing, the shortening of the AERP was most pronounced in the first 30 minutes and continued during pacing, physiological rate adaptation of the AERP was lost in the remodeled state, dispersion of the AERP increased, and inducibility and durtion of atrial fibrillation increased significntly. The AERP recovered the baseline 10 minutes after the cessation of pacing. In angiotensin-(l-7) group, shortening of the AERP was completely inhibited during rapid pacing, moreover AERP was longer than the baseline AERP and maintained the level of 2 hours after rapid pacing, physiological rate adaptation of the AERP was not lost, dispersion of the AERP did not changed, and inducibility and durtion of atrial fibrillation decreased. The AERP recovered the baseline 20 minutes after the cessation of pacing. There was no significantly difference in AERP shorteningbetween the control group and Ang II group, dispersion of the AERP increased, and inducibility and durtion of atrial fibrillation increased significntly. In mixed [Ang-(l-7) + Ang II ] group, AERP was lightly prolonged during the rapid pacing, the recovery of three sites was different. Dispersion of the AERP, inducibility and durtion of atrial fibrillation did not change. ConclusionsAngiotensin-(l-7) could inhibit the shortening of AERP during rapid atrial pacing effectively. This study indicates that Angiotensin-(l-7) may influence the atrial electrical remodeling and lead us to the better therapeutic management of human in subjects with atrial fibrillation.
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