The Effects Of Coronary Microembolization On The Microvascular Function And Cytokine Secretion

PART ONE The Animal Model of Intracoronary Microembolizationusing Catheterization TechniquesObjective: TO establish a pig model of coronary microembolizaton by use of catheterization techniques.Methods: Miniswines of either sex (20-25 kg body weight) were initially sedated with intramuscular injection of combination ketamine/diazepam (5-10 mg/kg). After endotracheal intubation, anesthesia was maintained by ventilation with 2% isoflurane. Sheaths, Heart rate obtained from the ECG. Intracoronary catheter (Cordis Rapidtransit 3/2.8Fr) was placed (monitored by fluoroscopy) in the proximal left anterior descending (LAD) artery for selective intracoronary infusion of microspheres (Diameter 45μm, 5 000 ml-1, E-Z Trac). Animals were sacrificed post operation 1 day, 7 days, 30 days to assess Hematoxylin & eosin (H&E) staining and nitroblue tetrazolium (NBT) dye as a morphological evidence of miroemolized myocardium.Results: Microspheres in the embolized artery and the inflammatory factors around it with H&E staining. In the embolized areas, a mix of microinfarcted (stained with wihite color and viable tissue could be observed, whereas nonembolized areas were devoid of microinfarctions (staining with blue color) dyed by NBT.Conclusions: Succeed in a pig model of coronary microembolizaton by use of catheterization techniques.Miniswine; Microembolization; Microshpere; Coronary; Animal modelCoronary flow reserve; Coronary blood flow; Endothelin-1; Microembolization; CytokinesObjects: To investigate the cytokines secretion (CME) causes progressive myocytes apoptosis and angiogenesis after coronary microembolization (CME).Methods: We induced CME in 27 miniswines by selective infusion of 15x104 microspheres (45μm) into left anterior descending artery (LAD). At baseline, Day 1 (Dl), 7 (D7) and 30 (D30), we measured 1) coronary sinus levels of IL-8, ET-1, IL-6, TNF-a using radioimmunioassay; 2) IL-6, IL-10, TNF-a, mast cell mRNA using RT-PCR; 3) expression of von-Willebrand factor (vWF) labeling as index of angiogenesis; 4) myocyte apoptosis by TUNEL assay, and 4) MC density using immunohistological staining and ultrastructal study using transmission electron microscopy. Coronary flow reserve (CFR) was assessed by Doppler wire over LAD at Dl, D7, D30 after CME. Four animals with injection of saline to LAD were served as control group.Results: After CME, the number of MCs, level of IL-6, IL-8, ET-1 and TNF (vs. baseline) increased significantly at Dl & D7 D30. Compared to baseline, CFR decreased significantly at Dl after CME but restored to baseline at D7 & D30. However, the number of myocyte apoptosis and angiogenesis increased significantly at Dl & D7 and further elevated at D30. There are significant positive correlations between the number of MCs with LV angiogenesis (r=0.63 with vWF, p<0.01) and myocardial apoptosis (r=0.84, p<0.01). ultrastructural study of mast cell (M) identified that Granules (G) derived from the degranuled-mast cell accumulated in area with collagen (C) and Fibroblast (F) deposition..Conclusions: After CME, MC accumulation is associated with an increase in myocardial level of IL-8 and TNF, angiogenesis and myocyte apoptosis. Despite restoration of CFR by angiogenesis, myocyte apoptosis persisted after CME. These findings suggest that MC play an important role in myocardial injury and repair after CME.