Effects Of Losartan On Remodeling In Rapid Atrial Pacing In Rabbits

Objective: Atrial fibrillation(AF) is the most common cardiac tachyarrhythmia in clinical. The disease rate of AF is raising up with the aging of the cociety and the raising of survival rate of the heart disease. It threatens the life time and the quality of life for causing thromboembolism and heart failure. The pathophysiology of AF is complex, and the mechanisms of AF are not completely understood at present. The modern research discovered that atrial electrical remodeling (AER) correlated closely with the AF. The purpose of this study was to investigate the electrical remodeling induced by rapid atrial pacing on rabbit model, by which the mechanisms of the electrical remodeling of AF may be analyzed. Additonally to investigate the effects of angiotensin receptor blocker losartan on atrial electrical remodeling and to propose a new idea on clinical approach of AF.Methods: A total of 30 healthy white rabbits no matter male or female were used in this study. After measured body weight and heart rate, rabbits were randomly divided into 3 groups: the saline group(Control group, n=10), saline pacing group(SN-P group, n=10), losartan pacing group (Los-P group, 2mg/(kg.d), n=10). Los-P group were injected losartan into stomach each day for one week and the other two group instead of saline as the same volume as the drugs. Then, The electrode catheter was localized in right atrium through right internal jugular vein. Surface ECG and right atrium electrogram were recorded. When the right atrium electrogram show amplitude of A ware we know the end of the electrode catheter had arrived right atrium. Fixed the electrode catheter after paced atrium and measured the pacing switch. The atrial effective refractory period (AERP) was measured by program stimulation at pacing cycle lengths of 200ms,190ms,180ms,170ms,160ms and 150ms respectively. Then, take a rapid atrial pacing (600 bpm) in SN-P and Los-P group, and the AERP was measured after 0.5,1,2,3,4,5,6,7 and 8 hours pacing in each group. Then killed the rabbits immediately and took out the heart. Tyrode's solution with calcium and Tyrode's solution without calcium were perfuse back to the heart each for 10min. Then took the tissue of right auricular appendage and cut them into little pieces. Solution of monoplast was prepared after the right auricular appendage tissue had been digested by collagenase. Measured the ICa-L within clipper voltage from -50mv to +50mv in 12 hours. The data of pa/pv when current density was the largest was taken to make statistical-analysis.SPSS10.0 software packs were used for all the data to make statistical-analysis. All values are expressed as mean±standard deviation. Continuous values were compared with repeated measurement date MANOVA in same group. One-way ANOVA was used to evaluate differences between groups of discrete variables. We tookα=0.05 as statistic significant level.Results: 1 The effect of rapid atrial pacing to AERP:In base condition (before pacing), the AERP at BCL from 200 to 150ms did not have significant deviation between NS-P group and NS group(P>0.05). The AERP at each BCL of NS group had no significant deviation with the time lasting from half an hour to 8 hours (P>0.05)(Fig 1 to Fig 6). The AERP at BCL from 200 to 150ms were significant shortened in NS-P group to compare with the NS group (P<0.01)(Table 1 to Table 6). after pacing for 8 hours, with the descending of the BCL equation of AERP between NS-P group and NS group were significant shortened (P<0.01)( Fig 8).2 Effects of Losartan on AERPIn base condition (before pacing), the AERP at BCL from 200 to 150ms did not have significant deviation between Los-P group and NS-P group (P>0.05). But after rapid atrial pacing, shortening of AERP in Los-P group was significant lightened than that of the NS-P group (P<0.01)( Table 1 to Table 6), but had no statistic significance as compared with the NS group. After rapid pacing for 8 hours, with the descending of the BCL the equation of AERP between Los-P group and NS group were not shortened(Fig8). Indicating that the physiological rate adaptation of the AERP was maintained in the remodeled state.3 Effect of rapid atrial pacing on ICa-LThe ICa-L of NS-P group was significant descendent as compared with the NS group. The ICa-L had no significant deviation between Los-P group and NS group. As compared with the NS-P group ,the ICa-L of Los-P group was not significant descended, but the standard deviation of ICa-L was significant descended (P<0.01)(Table8). This indicated that Losartan could inhibit the increasing of the straggling tendency resulted in rapid atrial pacing.Conclusions:1 Atrial rapid pacing can induce the atrial electrical remodeling (AER) characterized of the shortening of the AERP and the losting of physiological rate adaptation.2 Losartan can completely prevent not only the shortening of the AERP but also the lost of physiological rate adaptation by rapid atrial pacing.3 The shortening of ICa-L induced by rapid atrial pacing has not recovered after the pacing had stopped. And the straggling tendency resulted in rapid atrial pacing is heightened.4 Losartan can effectively prevent the heightening of straggling tendency of ICa-L resulted in rapid atrial pacing thereby can depress the potential risk of AF.