title: Cilostazol ameliorates atrial ionic remodeling in long-term rapid atrial pacing dogs.
abstract: OBJECTIVE
  Ionic remodeling has a close correlation with the occurrence of atrial fibrillation (AF). Atrial tachypacing remodeling is associated with characteristic ionic remodeling. The purpose of this study was to assess the efficacy of cilostazol, an oral phosphodiesterase 3 inhibitor, for preventing atrial ionic remodeling in long-term rapid atrial pacing (RAP) dogs.
  
  
  METHODS
  We use the methods of patch-clamp and molecular biology to investigate the effect of cilostazol on ion channel and channel gene expression in long-term RAP dogs. Twenty-one dogs were randomly assigned to sham, control paced, and paced+cilostazol (5 mg/kg/d, cilo) groups, with 7 dogs in each group. The sham group was instrumented with a pacemaker but without pacing. RAP at 500 beats/min was maintained for 2 weeks in the paced and cilo groups. During the pacing, cilostazol was given orally in the cilo group. Whole-cell patch-clamp technique was used to record atrial L-type Ca2+ (ICaL) and fast sodium channel (INa) ionic currents. Western blot and RT-PCR were applied to estimate the gene expression of the ICaLα) 1C (Cav1.2) and INav1.5α) Nav1.5α) subunits. Statistical analysis was performed using SPSS 13.0.
  
  
  RESULTS
  The density of ICaL and INa currents (pA/pF) was significantly reduced in the paced group (ICaL: -6.55±1.42 vs. -4.46±0.59 pA/pF; INa: -48.24±10.54 vs. -30.48±5.20 pA/pF, p<0.01). The paced+cilo group could not increase the density of ICaL currents (ICaL: -4.37±1.25 pA/pF, p>0.05), while the INa currents were recovered (-44.54±12.65 pA/pF, p<0.01) compared with the paced group. The mRNA and protein expression levels of Cav1.2 and Nav1.5α were apparently down-regulated in the paced group (p<0.01), but after cilostazol treatment, both of these subunits were up-regulated significantly (p<0.01).
  
  
  CONCLUSIONS
  Cilostazol may have protective effects on RAP-induced atrial ionic remodeling.
authors.affiliation: Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University; Tianjin-Republic of China. gp_limail@sina.com.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Zhao
authors.forename: Weimin
authors.initials: W
authors.lastname: Li
authors.forename: Xinghua
authors.initials: X
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Wansong
authors.initials: W
authors.lastname: Yang
authors.forename: Lijun
authors.initials: L
authors.lastname: Cheng
authors.forename: Enzhao
authors.initials: E
authors.lastname: Liu
authors.forename: Tong
authors.initials: T
authors.lastname: Liu
authors.forename: Guangping
authors.initials: G
authors.lastname: Li
mesh_terms: D000818:Animals; D064752:Atrial Remodeling / Q000187:drug effects*; D002304:Cardiac Pacing, Artificial; D000077407:Cilostazol; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D015870:Gene Expression; D008297:Male; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000187:drug effects* / Q000235:genetics; D018408:Patch-Clamp Techniques; D058987:Phosphodiesterase 3 Inhibitors / Q000494:pharmacology*; D011897:Random Allocation; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: D062554:NAV1.5 Voltage-Gated Sodium Channel; D058987:Phosphodiesterase 3 Inhibitors; D013777:Tetrazoles; D000077407:Cilostazol