Ischemic postconditioning inhibits apoptosis after acute myocardial infarction in pigs.
OBJECTIVE
Recent studies have shown that ischemic postconditioning reduces myocardial ischemia-reperfusion (I/R) injury; however, the effects of inhibiting apoptosis on cardioprotection induced by ischemic postconditioning remain to be determined. The objective of this study was to investigate whether ischemic postconditioning attenuates myocardial I/R injury by reduced apoptosis in a closed-chest pig model of acute myocardial infarction.


METHODS
Diannan small-ear pigs were randomly divided into 3 groups (5/group): (1) The sham group underwent a sham operation without ischemia; (2) the I/R group received 60 minutes of ischemia and 72 hours of reperfusion; and (3) the ischemic postconditioning (Postcond) group was treated the same as the I/R group except that the pigs received 8 cycles of 30 seconds of reperfusion and 30 seconds of ischemia at the onset of reperfusion. After 72 hours of reperfusion, infarct size was measured by 2,3,5-triphenyltetrazolium chloride staining. Apoptotic cells in the peri-infarct myocardium were evaluated with the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method, and apoptosis-related molecules were studied with western blotting analysis.


RESULTS
After 72 hours of reperfusion, mean (±SEM) infarct size was significantly smaller in the Postcond group than in the I/R group (23.26% ± 3.13% versus 10.89% ± 2.02%, P < .05). Apoptotic myocytes in the peri-infarct region were lower in the Postcond group than in the I/R group (15.31% ± 4.58% versus 33.83% ± 4.44%, P < .05). This decrease in the extent of apoptosis was accompanied by a significant decrease in Bax expression (0.306 ± 0.075 versus 0.433 ± 0.102 for the I/R group; P < .05) and a significant increase in Bcl-2 expression (1.801 ± 0.227 versus 1.267 ± 0.308 for the I/R group; P < .05).


CONCLUSIONS
In a clinically relevant closed-chest pig model of myocardial infarction, these data suggest the following: (1) Ischemic postconditioning reduces infarct size following prolonged reperfusion, and (2) this cardioprotective effect is likely achieved via antiapoptotic mechanisms.
Sun
Haimei
H
Department of ICU, The First Affiliated Hospital of Kunming Medical College, 295 Xin-Chang Road, Kunming, P. R. China.
Guo
Tao
T
Liu
Liu
L
Yu
Zhuo
Z
Xu
Wangbing
W
Chen
Wenhui
W
Shen
Lijuan
L
Wang
Jiaping
J
Dou
Xingkui
X
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D004195:Disease Models, Animal; D004562:Electrocardiography; D005500:Follow-Up Studies; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology*; D020287:In Situ Nick-End Labeling; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D013552:Swine; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein