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SummaryWe investigated the protective effect of ischaemic preconditioning (IP) on the maintenance of coronary patency using online measurements of coronary pressures and blood flow in a closed-chest reperfused acute myocardial infarction (MI) model in pigs. Catheter-based 90-min occlusion followed by 60-min reperfusion of the left anterior descending coronary artery (LAD) was performed in anesthetised pigs (MI group). IP was applied (IP group) through two cycles of 5-min occlusion and 5-min reperfusion of the LAD before MI induction. Coronary patency was determined by measurements of coronary wedge pressure, collateral fractional flow reserve (FFRcoll), collateral pressure index (CPI) and absolute coronary blood flow (CBF). Inducible and constitutive nitric oxide synthase (iNOS/cNOS) activities and expressions were determined in the myocardium. Plasma levels of myeloperoxidase (MPO, index of activated leukocytes) and mean platelet volume (MPV, index of activated platelets) were measured. IP resulted in significantly lower levels of MPO (0.52 ± 0.19 vs. 1.05 ± 0.24 U/l, p

SummaryEffects of ischaemic preconditioning (IP) on the mobilisation and recruitment of haematopoietic (HSCs) and mesenchymal stem (MSC) cells were determined in porcine coronary occlusion/reperfusion. Thirtythree pigs underwent percutaneous occlusion of the left anterior descending coronary artery (LAD) for 90 minutes (min), followed by 120 min reperfusion. IP was performed in 16 of the 33 pigs by two cycles of 5 min balloon occlusion/reperfusion prior to the 90 min occlusion (group IP vs. group C). Peripheral blood and myocardial tissue concentration of bone marrow origin HSCs (characterised by coexpression of CD31+, CD90+, CD45+) and MSCs (characterised by coexpression of CD44+, CD90+, CD45-) were measured by flow cytometry in the early phase of IP. Plasma/serum levels of stem cell mobilisation factors (stromal cell-derived factor-1α [SDF-1α], vascular endothelial growth factor [VEGF], tumour necrosis factor α[TNF-α] and interleukin-8 [IL-8]) were measured. IP led to a significant increase in circulating HSCs as compared with the group C (475 ± 233 vs. 281 ± 264 /μl, p=0.032) in the early phase of IP. In contrast, a rapid and prolonged decrease in level of circulating MSCs was observed in group IP as compared with group C (19 ± 12 vs. 32 ± 17 /μl, p=0.015). The recruitment of HSCs and MSCs in infarct and border zone was significantly greater in IP group, indicating a faster homing of MSCs as compared with the rate of mobilisation. Rapid increase in VEGF, TNF-α and IL-8 levels was induced by IP, which, however, was not correlated with the levels of circulating SCs. In conclusion, IP resulted in differential mobilisation and recruitment of HSCs and MSCs in the early phase of cardioprotection.

SummaryIncreased thrombogenicity of drug-eluting stents (DESs) has recently been reported.The aim of the present study was to investigate the prothrombogenic effect of DESs and Bare stents, and determine factors predictive of acute stent thrombosis (AST) in preclinical experiments using new stent design or coating.Circulating preand post-stenting parameters of platelet activation (mean platelet volume, MPV; platelet distribution width, platelet large cell ratio), thrombin activation (thrombin-antithrombin complex, TAT and prothrombin fragments, F1+2), tissue factor antigen (TF-ag) and -activity (TF-act) and plasminogen activator inhibitor-1 (PAI-1) were measured in 141 consecutive pigs. Stent implantations were performed after pretreatment with aspirin and clopidogrel with unfractionated heparin anticoagulation. Nineteen pigs (groups AST-DES, n=12; and AST-Bare, n=7) died mean 6.3 ± 2.9 h after stent implantation from AST.The remaining 122 control (C) pigs (groups C-DES,n=76,and C-Bare,n=46) survived the 1-month follow-up. Non-significantly elevated levels of post-stent F1+2 and TAT were measured in AST groups. Post-stenting MPV was increased significantly in the groups ASTDES and AST-Bare as compared with the groups C-DES and C-Bare (11.73 ± 1.12 and 11.6 ± 0.68 vs. 8.85 ± 0.78 and 9.04 ± 0.81 fL; p