| Peripheral artery disease (PAD) severely damaged the function of the limb and threatened the quality of life of the patients. PAD was significantly increased the risk of coronary artery disease, stroke, aortic aneurysm and renal failure. In the "Twelfth Five Year Plan" period, China's rapid aging. There will be more than 220 million population aged more than 65 years. Improving prevention, detection, treatment and healthcare of PAD are urgent. Patients' general condition and other combined diseases must be taken into consideration in the treatment. The current surgical treatment includes arterial reconstruction surgery and endovascular treatment technology. Due to minimally invasive characteristics and clinical effectiveness,endovascular treatment developed rapidly. Recently, drug-coated balloon in the treatment of coronary artery disease has achieved satisfactory results, but still lack of evidence in the treatment of lower extremity arterial occlusive disease.In the first part, Pharmacokinetics evaluation of the drug released and tissue uptake were determined in the arteries by analyzing the drug concentration in blood and various tissues at 1h, 24 h, 3, and 7 days.Introduction of paclitaxel-coated balloon to the arteries and retraction without inflation resulted in 13.92% loss of all paclitaxel content. After the dilatation, most of the paclitaxel was released during the inflation.(1) The remained content of paclitaxel on the balloon was similar for different inflation time,63±9.14?g (8.36%) for 60 s inflation, 62.71±12.87?g(8.32%) for 180 s, and 62.94±19.09?g (8.35%)for 300 s; (2) With the inflation for 60 s, 180 s,and 300 s,the paclitaxel content in the artery wall was 58.91±28.08?g/g,272.9±127.9p,g/g, and 317.2±72.76?g/g; (3) With the inflation for 180 s, the paclitaxel content in the artery wall was 272.9±127.9?g/g after one hour,127.9±65.14?g/g after 24 hours, 33.43±20.31?g/g after 3 days, 13.56±5.89?g/g after 7 days; (4) The drug concentration in blood was 17.21 ng/ml in one hour, 19.50 ng/ml in six hours, 22.33 ng/ml in twelve hours, 30.67 ng/ml in 24 hours, 42.82ng/ml in three days, and 31.38 ng/ml in seven days; (5) The drug concentration in different follow-up time (1h,24h, 3d,7d) was 26.89 ng/g,392.78 ng/g,231.41 ng/g,and 176.95 ng/g in cardiac tissue, 23.2 ng/g, 425.12 ng/g , 221.69 ng/g and 239.26 ng/g in hepatic tissue, 886.96 ng/g.955.35 ng/g.217.16 ng/g, 253.36 ng/g in spleen tissue, 886.96 ng/g.955.35 ng/g.217.16 ng/g and 253.36 ng/g in lung tissue.In the second part, we evaluated the effectiveness and safety of a domestic paclitaxel-eluting balloon in the porcine peripheral artery restenosis models by using optical coherence tomography, quantitative vascular angiography, scanning electron microscopy and other methods. The safety results (1) Experimental animals did not occur any device-related adverse events; (2) All organs and tissues of all experimental animals were normal; (3 ) Scanning electron microscopy showed that the endocytosis of the drug-eluting balloon group was weaker than that of the uncoated balloon group at the 28th day, and the two groups were completely endothelialized at 90 days. The effectiveness results (1) The QVA analysis showed that the luminal loss in the drug-coated balloon group and uncoated balloon group are 1.05±0.87 mm and 1.29±0.68 mm (p>0.05) , and the percentage of stenosis in the two groups was 21.12 ± 16.70% and 24.34 ± 11.95% (p> 0.05) in 28th day,respectively. The luminal loss in the two groups was 1.01 ±0.29 mm and 1.19±0.51 mm (p>0.05) , and stenosis in the two groups was 22.97±7.61% and 24.71±7.98%(p>0.05) in 90th day, respectively; (2) The OCT results showed that the two groups were completely covered with endothelial cells in all time points; (3)Endometrial hyperplasia was more severe in the common balloon group than in the drug-coated balloon group in 28 days and 90 days. The results showed the paclitaxel-eluting balloon was safe to use in the animal experiments. |
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