Abstract 16466: Impaired Function of Circulating CD34+/KDR+ Endothelial Progenitor Cells in Patients With Persistent Atrial Fibrillation is Restored by the Calcium Channel Blocker Bepridil Hydrochloride
Background: Despite accumulating evidence regarding the occurrence of endothelial dysfunction in chronic atrial fibrillation (AF) patients, little is still known about the number and function of circulating endothelial progenitor cells (EPCs) in AF. Bepridil hydrochloride (BEP), which is primarily used only in Japan but not in other advanced countries, is a multiple ion channel blocker that has exhibited efficacy for the pharmacological conversion of persistent AF. In the present study, we examined the number and function of circulating EPCs in persistent AF patients and the effect of BEP treatment on EPCs.
Methods and Results: The number of circulating CD34+/KDR+ EPCs was determined by [[Unable to Display Character: ﬂ]]ow cytometry in 18 consecutive patients with persistent AF [the mean age was 62 ± 5.2 years of age, male subjects comprised 67% of the series] prior to pharmacological conversion by BEP, and they were compared with age- and sex-matched controls. BEP was administered beginning at a daily dose of 100 mg and thereafter was increased up to a maximum of 200 mg for 90 days. Higher levels of circulating CD34+/KDR+ cells were observed in patients with persistent AF in comparison to the control subjects [0.12 ± 0.04% vs 0.05± 0.02% CD34+/KDR+ cells in the MNC fraction, p<0.041]. However, the EPCs from patients with persistent AF exhibited an impaired migration towards stromal cell derived factor (SDF)-1 and human serum. BEP did not significantly change the number of EPCs, but it did restore the ability of these cells to migrate towards SDF-1 and human serum. These findings suggest that EPCs from patients with persistent AF are mobilized into the circulation, but they may be unable to migrate and repair damaged capillary endothelium in atria. BEP may have a beneficial effect on the function of these impaired EPCs.
Conclusion: The number of EPCs was observed to increase, but the EPC function was impaired in patients with persistent AF. The multiple ion channel blocker BEP may therefore have a beneficial effect on the pharmacological conversion of persistent AF by helping to restore the EPC function.
- Atrial fibrillation
- Calcium channel blockers
- Endothelial progenitor cell
- Atrial defibrillation
- © 2013 by American Heart Association, Inc.