[Ischemic preconditioning attenuates myocardial no-reflow and reperfusion injury after revascularization of acute myocardial infarction by reducing myocardial edema via the protein kinase A pathway].
OBJECTIVE
Myocardial edema plays an important role in the development of myocardial no-reflow and reperfusion injury after the revascularization of acute myocardial infarction (AMI). The present study investigated whether the effect of ischemic preconditioning (IPC) against myocardial no-reflow and reperfusion injury was related to the reduction of myocardial edema through the protein kinase A (PKA) pathway.


METHODS
Twenty-four minipigs were randomized into sham, AMI, IPC, and IPC + H-89 (PKA inhibitor, 1.0 µg · kg(-1) · min(-1)) groups. The area of no-reflow (ANR), area of necrosis (AN), and water content in left ventricle and ischemic-myocardium and non-ischemic area were determined by pathological studies. Microvascular permeability was determined by FITC-labeled dextran staining. Cardiomyocyte cross-sectional area (CSA) and mitochondria cross-sectional area (MSA) were evaluated by histological analysis. Myocardial expression of aquaporins (AQPs) was detected by Western blot.


RESULTS
Compared with the MI group, the sizes of no-reflow and infarct were reduced by 31.9% and 46.6% in the IPC group (all P < 0.01), water content was decreased by 5.7% and 4.6% in the reflow and no-reflow myocardium of the IPC group (all P < 0.05), microvascular permeability and cardiomyocytes swelling in the reflow area were inhibited by 29.8% and 21.3% in the IPC group (all P < 0.01), mitochondrial water accumulation in the reflow and no-reflow areas of the IPC group were suppressed by 45.5% and 34.8% respectively (all P < 0.01), and the expression of aquaporin-4, -8, and -9 in the reflow and no-reflow myocardium were blocked in the IPC group. However, these beneficial effects of IPC were partially abolished in the IPC + H-89 group.


CONCLUSIONS
The cardioprotective effects of IPC against no-reflow and reperfusion injury is partly related to the reduction of myocardial edema by inhibition of microvascular permeability and aquaporins up-regulation via PKA pathway.
Department of Evidence Based Medicine, Fuwai Hospital and National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
Xiang-dong
XD
Li
Yue-jin
YJ
Yang
Jing-lin
JL
Zhao
Hai-tao
HT
Zhang
Yu-tong
YT
Cheng
Yi
Y
Tian
Xian-min
XM
Meng
He-he
HH
Cui
Tian-Jie
TJ
Wang
D000818:Animals; D020346:Aquaporins / Q000378:metabolism; D002199:Capillary Permeability; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004487:Edema / Q000378:metabolism / Q000473:pathology; D019194:Ischemic Preconditioning; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D013552:Swine; D013556:Swine, Miniature
D020346:Aquaporins; D017868:Cyclic AMP-Dependent Protein Kinases