title: Post-conditioning with gradually increased reperfusion provides better cardioprotection in rats.
abstract: BACKGROUND
  Rapid and complete reperfusion has been widely adopted in the treatment of patients with acute myocardial infarction (AMI), but this process sometimes can cause severe reperfusion injury. This study aimed to investigate different patterns of post-conditioning in acute myocardial ischemia-reperfusion injury, and to detect the role of mitogen activated protein kinase (MAPK) during the injury.
  
  
  METHODS
  RATS WERE RANDOMLY DIVIDED INTO FIVE GROUPS: sham group, reperfusion injury (R/ I) group, gradually decreased reperfusion group (GDR group, 30/10-25/15-15/25-10/30 seconds of reperfusion/ischemia), equal reperfusion group (ER group, 20/20 seconds reperfusion/ischemia, 4 cycles), and gradually increased reperfusion group (GIR group, 10/30-15/25-25/15-30/10 seconds of reperfusion/ischemia). Acute myocardial infarction and ischemic post-conditioning models were established in the rats. Six hours after reperfusion, 3 rats from each group were sacrificed and myocardial tissues were taken to measure the expressions of phosphorylation of extracellular signal-regulated protein kinase (P-ERK), phosphorylated c-Jun N-terminal kinase (P-JNK), mitogen-activated protein kinase p38 (p38 MAPK), tumor necrosis factor-α (TNF-α), caspases-8 in the myocardial tissue, and cytochrome c in the cytosol using Western blot. Hemodynamics was measured at 24 hours after reperfusion, the blood was drawn for the determination of cardiac enzymes, and the heart tissue was collected for the measurement of apoptosis using TUNEL. One-way analysis of variance and the Q test were employed to determine differences in individual variables between the 5 groups.
  
  
  RESULTS
  Three post-conditioning patterns were found to provide cardioprotection (P<0.05) compared with R/I without postconditioning. GIR provided the best cardioprotection effect, followed by ER and then GDR. Apoptotic index and serum marker levels were reduced more significantly in GIR than in ER (P<0.05). The enhanced cardioprotection provided by GIR was accompanied with significantly increased levels of P-ERK 1/2 (1.82±0.22 vs. 1.54±0.32, P<0.05), and lower levels of p-JNK, p38 MAPK, TNF-α, caspase-8, caspase-9 and cytochrome in the cytoplasm (P<0.05), compared with ER. The infarct size was smaller in the GIR group than in the ER group, but this difference was not significant (16.30%±5.22% vs. 20.57%±6.32%, P<0.05). All the measured variables were improved more significantly in the GIR group than in the GDR group (P<0.05).
  
  
  CONCLUSIONS
  Gradually increased reperfusion in post-conditioning could attenuate reperfusion injury more significantly than routine method, thereby the MAPK pathway plays an important role in this process.
authors.affiliation: Department of Cardiology, General Hospital of Jinan Military Command, Jinan 250031, China ; Institute of Geriatric Cardiology, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Guo-Ming
authors.initials: GM
authors.lastname: Zhang
authors.affiliation: Institute of Geriatric Cardiology, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Cardiovascular Institute, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Tian-de
authors.initials: TD
authors.lastname: Li
authors.affiliation: Department of Cardiology, General Hospital of Jinan Military Command, Jinan 250031, China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Li
authors.affiliation: Department of Outpatient, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Shao-Ping
authors.initials: SP
authors.lastname: Su
authors.affiliation: Department of Ultrasound, General Hospital of Jinan Military Command, Jinan 250031, China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Sun
authors.affiliation: Department of Pathophysiology, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Xiu-Hua
authors.initials: XH
authors.lastname: Liu
keywords: Apoptosis; Ischemia-reperfusion injury; Postconditioning