Mouse Abdominal Aortic Aneurysm Model Induced by Periarterial Incubation of Papain.

For decades, numerous experimental animal models have been developed to examine the pathophysiologic mechanisms and potential treatments for abdominal aortic aneurysms (AAAs) in diverse species with varying chemical or surgical approaches. This study aimed to create an AAA mouse model by the periarterial incubation with papain, which can mimic human AAA with advantages such as simplicity, convenience, and high efficiency. Eighty C57BL/6J male mice were randomly assigned to 1 of the 4 groups: papain (1.0 or 2.0 mg), porcine pancreatic elastase, and phosphate-buffered solution. The aortic segment was wrapped for 20 minutes, and the diameter was measured using ultrasound preoperatively and postoperative days 7 and 14. Then, the mice were killed for histomorphometric and immunohistochemical analyses. According to ultrasound measurements and histomorphometric analyses, on postoperative day 7, 65% of mice in the 1.0-mg papain group and 60% of mice in the 2.0-mg papain group developed AAA. In both papain groups, 100% of mice developed AAA, and 65% of mice in the porcine pancreatic elastase group developed AAA on postoperative day 14. Furthermore, hematoxylin/eosin, elastin van Gieson, and Masson staining of tissues from the papain group revealed thickened media and intimal hyperplasia, collagen sediments, and elastin destruction, indicating that AAA histochemical alteration was similar to that of humans. In addition, the immunohistochemical analysis was conducted to detect infiltrated inflammatory cells, such as macrophages and leukocytes, in the aortic wall and hyperplasic adventitia. The expression of matrix metalloproteinase 2 and 9 was significantly upregulated in papain and human AAA tissues. Periarterial incubation with 1.0 mg of papain for 20 minutes can successfully create an experimental AAA model in mice for 14 days, which can be used to explore the mechanism and treatment of human AAA.

Comparison between paclitaxel-coated balloon and standard uncoated balloon in the treatment of femoropopliteal long lesions in diabetics.

Atherosclerotic diseases may include femoropopliteal artery stenosis or occlusion. Percutaneous transluminal angioplasty (PTA) is an effective and minimally invasive treatment strategy for atherosclerotic femoropopliteal artery stenosis/occlusion disease. Balloon angioplasty is a widely used technique in the management of occlusive disease in almost all arterial segments.We enrolled 111 diabetics with long femoropopliteal lesions, among which 54 received PTA with paclitaxel-coated balloon (the Paclitaxel group), and 57 with standard balloon catheters (the Control group).The primary outcome was set as angiographic late lumen loss (LLL) within 6 months; the secondary angiographic outcome was binary restenosis. Clinical outcomes included Rutherford clarification, ankle-brachial index (ABI) and rate of clinically driven target lesion revascularization (TLR). Two groups had similar basal clinical features, angiographic and procedural characteristics. Compared to controls, the Paclitaxel group had a significantly lower 6-month LLL rate, 12-month binary restenosis rate, 12-month TLR, lower Rutherford grades at 3 and 6 months, and higher ABI at 3 months. For all factors which might influence outcomes, fasting blood glucose was negatively correlated with ABI; the blood urea nitrogen (BUN) was positively related with the Rutherford clarification grades. In addition, the coronary heart disease (CHD) and smoking histories were positively correlated with residual stenosis after treatment.Collectively, the paclitaxel-coated balloon angioplasty can yield more favorable angiographic and clinical outcomes than standard uncoated balloon angioplasty, even in the more challenging lesions (the long and occlusive femoropopliteal lesions) in diabetics, when it had a similar safety profile to the traditional balloon. Blood glucose, BUN, CHD, and smoking imply poor curative effects.

Ryanodine receptor antagonism alleviates skeletal muscle ischemia reperfusion injury by modulating TNF-α and IL-10.

BACKGROUND: Intracellular calcium overload has been implicated in various pathological conditions including ischemia reperfusion injury. This study aims to explore the effect and probable mechanism of dantrolene, a ryanodine receptor and intracellular calcium antagonist, on the skeletal muscle ischemia reperfusion injury. MATERIALS AND METHODS: SD rats were randomly divided into three groups: sham group which underwent anaesthesia and exposure of femoral vein, reperfusion group that received 2 h ischemia and the amount of diluent via femoral vein before 4 h reperfusion, dantrolene group that underwent 2 h ischemia and was given 2 mg/kg dantrolene via femoral vein before 4 h reperfusion. The parameters measured at the end of reperfusion included serum maleic dialdehyde (MDA), tissue myeloperoxidase (MPO) and muscle histology, as well as serum TNF-α and IL-10. RESULTS: Levels of MDA, MPO and TNF-α increased in the reperfusion group, whereas the relevant expressions in the dantrolene group decreased significantly. Histological examination demonstrated significant improvements between the same both groups. IL-10 reflected the protection observed above with a significant up-regulation of expression after dantrolene administration. CONCLUSION: Ryanodine receptor antagonist dantrolene exerted a significant protective effect against the inflammatory injury of skeletal muscle ischemia reperfusion. The underlying molecular mechanism is probably related to the suppression of TNF-α levels and the increment of IL-10 expression.