title: [Influence of oxidative stress on atrial myocardium pathohistological and ultrastructural changes in atrial fibrillation: experiment with dogs].
abstract: OBJECTIVE
  To evaluate the effects of oxidative stress on the protein expression of atrial calpain I and pathohistological and ultrastructural changes of atrial myocardium in atrial fibrillation (AF).
  
  
  METHODS
  Twenty dogs were all implanted with pacemaker in a subcutaneous pocket and attached to a screw-in epicardial lead in right atrial appendage. They were randomly divided into 3 groups: sham-operation group (n = 6 without pacing), control group (n = 7 per minutes for 6 weeks), and probucol group (n = 7, pacing 1 week after recovery for 6 weeks, and administration of probucol 100 mg x kg(-1) x d(-1) 1 week before pacing till the end of pacing). One thin silicon plaque containing 4 pairs of electrodes were sutured to the right atrium. The dogs in control group, probucol group were paced at 400 beats per minutes for 6 weeks. Then the dogs were killed with their hearts taken out. The expression of atrial calpain I was measured by Western-blotting and immunohistochemistry. The pathohistological and ultrastructural changes in atrial tissue were tested by light and electron microscopy. The inducibility and duration of AF were measured in the control group and probucol group. The indexes of oxidative stress total anti-oxidation capability (T-AOC), malonyldiadehyde (MDA), and scavenging activities of superoxide anion (O2-) radical were measured by colorimetric method.
  
  
  RESULTS
  The percentage of myolysis in the left and right atria of the control group were (53.6 +/- 11.8)% and. (58.5 +/- 9.2)% respectively, significantly higher than those of the sham operation group [(4.4 +/- 3.1)% and (4.1 +/- 2.9)% respectively, both P < 0.01]. The percentage of myolysis in the left and right atria of the probucol group were (12.3 +/- 3.2)% and (12.0 +/- 2.6)% respectively, both significantly lower than those of the control group (both P < 0.01). The protein expression of calpain I of the control group was significantly higher than that of the sham-operation group, and the protein expression of calpain I of the probucol group was significantly lower than that of the control group. The AF inducibility rate after pacing of the probucol group was 60%, significantly lower than that of the control group (92.9%, P < 0.01). The average AF duration time after pacing of the probucol group was (601 +/- 328) s, significantly shorter than that of the control group (1458 +/- 498) s. The indexes of oxidative stress in probucol group were lower than the level in control group. The MDA levels of the probucol group was (3.08 +/- 0.20) mmol/mg protein, significantly lower than that of the control group (4.15 +/- 0.23) mmol/mg protein). The anti-O2- and T-AOC level of the probucol group were 279 +/- 20 U/g protein and 30.5 +/- 1.3 nmol/mg protein, both significantly higher than those of the control group (215 +/- 16 U/g protein and 25.6 +/- 1.5 nmol/mg protein respectively, both P < 0.01). There were more sarcomere vacuolization and dissolution in atrial myocytes in the control group than in the sham operation group. And the pathohistological and ultrastructural changes of the probucol were lighter than those of the control group.
  
  
  CONCLUSIONS
  Probucol prevents the pathohistological and ultrastructural changes in atrial myocardium by inhibiting calpain I expression, thus suppressing atrial structural remodeling, and preventing the induction and promotion of AF.
authors.affiliation: Department of Cardiology, First Clinical Hospital, Harbin Medical University, Harbin 150001, China.
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Sheng
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.forename: Bao-Feng
authors.initials: BF
authors.lastname: Yang
authors.forename: Yong-Tai
authors.initials: YT
authors.lastname: Gong
authors.forename: Hong-Jie
authors.initials: HJ
authors.lastname: Xue
authors.forename: Jiang-Bo
authors.initials: JB
authors.lastname: Yu
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Hong-Bo
authors.initials: HB
authors.lastname: Shan
authors.forename: Jie
authors.initials: J
authors.lastname: Liu