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
10.3760/cma.j.issn.0253-3758.2012.11.011
- VernacularTitle:缺血预适应改善猪急性心肌梗死再灌注后无复流和再灌注损伤的作用与通过蛋白激酶A通路减轻心肌水肿有关
- Author:
Xiang-Dong LI
1
;
Yue-Jin YANG
;
Jing-Lin ZHAO
;
Hai-Tao ZHANG
;
Yu-Tong CHENG
;
Yi TIAN
;
Xian-Min MENG
;
He-He CUI
;
Tian-Jie WANG
Author Information
1. 100037,中国医学科学院北京协和医学院阜外心血管病医院心血管疾病国家重点实验室群体遗传研究室和循证医学部
- Keywords:
Myocardial infarction;
Myocardial reperfusion injury;
Edema
- From:
Chinese Journal of Cardiology
2012;40(11):945-951
- CountryChina
- Language:Chinese
-
Abstract:
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.
