The Effect Of Rennin-Angiotensin System On The Acute Atrial Remodeling Induced By Rapid Atrial Pacing In Dogs

Objective To investigate the effect of the rennin-angiotensin system (RAS) on the acute atrial electrical remodeling in canine, and evaluate the effect of angiotensin-(1-7) [Ang-(1-7)], angiotensin II (Ang II) and angiotensin converting enzyme inhibitior (ACEI) (captopril) on acute atrial electrical remodeling in canine model of AF both induced by short-term rapid pacing at the high right atrium (HRA), we observed changes of atrial electrophysiological characteristics, including the atrial effective refractory period (AERP), the AERP dispersion, the rate adaptation of the AERP, the incidence and duration of secondary atrial fibrillation (AF).Methods Twenty healthy mongrel dogs were randomly divided into control, Ang-(1-7), Ang II and captopril groups, In each group, infusion of 5% glucose saline, Ang-(1-7), Ang II and captopril (ACEI) were given respectively, In each dog, one bipolar pacing electrode was sutured onto the high right atrial (HRA) epicedium and three bipolar recording electrodes were respectively sutured onto the low right atrial (LRA), the high left atrial (HLA), the low left atrial (LLA) epicedium. After measurement of atrial electrophysiological characteristics at baseline, acute AF was induced by rapid atrial pacing with a cycle length (S₁S₁) of 100 ms. Rapid pacing was maintained for 2 hours and was briefly interrupted every 30minutes for the first hour and thereafter once per hour for the duration of rapid pacing to allow for repeated assessment of AERP by S₁S₂ programmed stimulation at 3 deferent basic (S1S1) cycle lengths (BCLs) (200ms, 250ms, 350ms). Finally, measurements were made every 10 minutes for 30 minutes after the cessation of pacing stimulation.Results In the control group, AERP shortening began and was most pronounced in the first 30 minutes and continued during pacing. After 2 hours of rapid pacing, AERP was significantly shortened at all 3 cycle lengths at 3 positions,and the dispersion of the AERP was significantly increased with insufficiency of the physiological rate adaptation of the AERP. The incidence and duration of the secondary AF were also significantly increased. After the termination of rapid pacing, the AERP in the control group gradually increased, the AERP at all of the BCLs and all positions examined recovered to almost the baseline value within the first 10 minutes. There were no significant differences in changes of atria! electrophysio-logical characteristics between Anglland control group. But in the Ang II group , AERP at 10 minutes after the cessation of rapid pacing was still shorter than the baseline value, and it took 20 minutes to recover to the baseline value. Thus, Ang II infusion produced a distinct delay in the recovery from electrical remodeling after the cessation of rapid pacing. In the Ang-(l-7) group and captopril-treated group, the AERP was no longer shortened by rapid pacing. At the same time, AERP after the termination of rapid pacing was still longer than the baseline value. After 2 hours of rapid pacing, the AERP dispersion of the two groups was not changed significantly, and the incidence and duration of secondary AF were no significant difference compared with baseline. In contrast to the control group, Ang-(l-7) and captopril maintained physiological rate adaptation and completely prevented atrial electrical remodeling.Conclusion1. AF induced by rapid atrial pacing and atrial stimulation can produce shortening of the AERP and reverses the normal physiological rate adaptation of the AERP, so they can produce the phenomenon of atrial electrical remodeling.2. RAS play an important role on the produce and maintenance of the acute atrial electrical remodeling induced by rapid pacing.3. The shortening of the AERP during rapid pacing can be prevented by treatment with Ang-(l-7), and physiological rate adaptation of the AERP was maintained in Ang-(l-7) group. These results suggest that Ang-(l-7) can prevent acute atrial electrical remodeling induced by rapid pacing.4. Ang-(1 -7) may have some effect on the prevention and therapy of AF.