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Objective: To explore the synergistic protection of Danhong Injection ([Chinese text], DHI) and ischemic postconditioning on myocardial reperfusion injury in minipigs. Methods: Acute myocardial infarction model was made by balloon occlusion in left anterior descending coronary artery (LAD) of minipigs, and then postconditioning was simulated through inflation/deflation of the angioplasty balloon. Minipigs were divided into four groups: the sham operation group (SH group), the ischemia/reperfusion group (I/R group), the ischemic postconditioning group (POC group) and DHI combined with ischemic postconditioning group (PAD group, DHI 20 mL through ear vein), six in each group. After 24-h continuous observation, myocardial infarction size was assessed by triphenyltetrazolium staining (TTC). Morphological changes of ischemic myocardium were observed by light microscopy, and cardiomyocyte ultrastructure was studied with electron microscopy. The superoxide dismutase (SOD) and malondialdehyde (MDA) activity in heart homogenates were measured by a biochemical method. Results: The myocardial infarction size was smaller in the POC group than in the I/R group (0.26±0.02 vs. 0.37±0.09, P<0.05), and the PAD group (0.14±0.08) displayed a significantly reduced infarction size relative to the I/R group (P<0.01) and POC group (P<0.05). The damage of myocardial tissue was severe in the I/R group shown by light and electron microscopy: myocardial fibers disorder, sarcoplasmic dissolution, myofilament fracture, mitochondria swelling and even vacuolization formation and a large number of inflammatory cell infiltrations. Compared with the I/R group, reduction of reperfusion injury in the PAD group included more orderly arranged myocardial fibers, less infiltration of inflammatory cells and maintenance of mitochondrial integrity. Compared with the I/R group, the damage of myocardial tissue in the POC group was improved, but not as significant as that in the PAD group. SOD levels in the POC group and the PAD group were significantly higher than those in the I/R group (96.96±13.43, 112.25±22.75 vs. 76.32±10.63, P<0.05), and MDA was significantly lower in the POC group and the PAD group compared to the I/R group (1.27±0.19, 1.09±0.21 vs. 1.47±0.16, P<0.05). Conclusion: DHI and ischemic postconditioning show a synergistic cardioprotection on myocardial reperfusion injury in minipigs. [ABSTRACT FROM AUTHOR]