Published in:
01-10-2007
Angiotensin II Type 1 Receptor Inhibition is Associated with Reduced Tachyarrhythmia-Induced Ventricular Interstitial Fibrosis in a Goat Atrial Fibrillation Model
Authors:
Stavros I. Chrysostomakis, Ioannis K. Karalis, Emmanuel N. Simantirakis, Anastasios V. Koutsopoulos, Hercules E. Mavrakis, Gregory I. Chlouverakis, Panos E. Vardas
Published in:
Cardiovascular Drugs and Therapy
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Issue 5/2007
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Abstract
Background
Using a goat animal model, we tested the hypothesis that angiotensin-II inhibition reduces fibrotic degeneration of both the atrial and ventricular myocardium as well as AF induction susceptibility.
Methods
We studied three groups of five goats over a 6-month period. The study animals in the first two groups were implanted with a pacemaker capable of maintaining AF with burst pacing. Additionally, in one group, goats were administered candesartan (AF+candesartan group). The third group (SR group) of animals served as control. Animals were tested for AF induction on day 0, 1, 30, 90 and 180. A “Vulnerability Index” (VI) for AF induction was calculated, defined as the ratio of total time in AF per number of bursts needed to induce sustained AF, in each session. At the end of the study, all four heart chambers were examined and fibrosis quantified.
Results
Both AF goat groups developed cardiomegaly due to tachy-cardiomyopathy. Although, the VI was significantly increased in AF group over time (28.8 ± 43 to 284.7 ± 291, p = 0.045), this was not the case for AF+candesartan group (30.3 ± 40 to 170.8 ± 243, p = 0.23). Histology revealed a significant increase of fibrous tissue in goats with induced AF, noticeable in all four heart chambers, compared to controls. However, the degree of fibrosis was significantly lower in AF animals on candesartan.
Conclusions
Our study demonstrated a beneficial effect of angiotensin II inhibition on tachyarrhythmia-induced ventricular fibrosis. It is also consistent with previous studies indicating a reduction in burst-induced AF susceptibility in goats and confirms the favorable effects in atrial structural remodeling.