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.
Department of ICU, The First Affiliated Hospital of Kunming Medical College, 295 Xin-Chang Road, Kunming, P. R. China.
Haimei
H
Sun
Tao
T
Guo
Liu
L
Liu
Zhuo
Z
Yu
Wangbing
W
Xu
Wenhui
W
Chen
Lijuan
L
Shen
Jiaping
J
Wang
Xingkui
X
Dou
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