phosphorus-radioisotopes and Arteriosclerosis

Three-month studies of stent-delivered brachytherapy in the rabbit model show reduced neointimal growth. However, intimal healing is delayed, raising the possibility that intimal inhibition is merely delayed rather than prevented. The purpose of this study was to explore the long-term histological changes after placement of beta-emitting radioactive stents in normal rabbit iliac arteries.. Three-millimeter beta-emitting (32)P stents (6, 24, and 48 microCi) were placed in normal rabbit iliac arteries with nonradioactive stents as controls. Animals were euthanatized at 6 and 12 months, and histological assessment, morphometry, and analysis of endothelialization were performed. Morphometric measurements demonstrated a >50% reduction in intimal growth and percent lumen stenosis within 24- and 48-microCi stents versus control nonradioactive stents at both 6 and 12 months. However, the 24- and 48-microCi stents also showed delayed healing of the intimal surface, characterized by persistent fibrin thrombus with nonconfluent areas of matrix, incomplete endothelialization, and increased intimal cellular proliferation. Stent edge stenosis was present at 12 months in the 24- and 48-microCi stent groups, characterized by both intimal thickening and negative arterial remodeling.. Inhibition of intimal growth is maintained 6 and 12 months after (32)P beta-emitting stent placement. However, delayed arterial healing, incomplete endothelialization, and edge effects are present.

Topics: Animals; Arteriosclerosis; Cell Division; Endothelium, Vascular; Fibrin; Iliac Artery; Male; Microscopy, Electron, Scanning; Phosphorus Radioisotopes; Rabbits; Stents; Time Factors; Tunica Intima

According to early clinical trials, vascular brachytherapy performed prior to or shortly after angioplasty is very effective in reducing restenosis rates. The purpose of this study was to investigate the effects of a novel radioactive catheter that allows simultaneous balloon angioplasty and beta-particle irradiation in the prevention of restenosis.. The balloon surface of an angioplasty catheter was impregnated with the radioisotope(32)P. Dosimetry calculations using a Monte Carlo method were performed at a radial distance of 0.2 mm from the balloon surface. Rabbit iliac arteries were dilated and simultaneously irradiated with a dose of 20 Gy delivered to the adventitia. Control arteries were only dilated and not irradiated. Neointimal areas, cell numbers and the perimeter of the arteries were measured by histomorphometry after 6 weeks.. Neointima formation was reduced after balloon dilatation and simultaneous beta-particle irradiation using the(32)P impregnated angioplasty catheter as compared to balloon dilatation alone with a non-impregnated catheter (0.09+/-0.06 vs 0.27+/-0.09 mm(2)neointimal area and 168+/-45 vs 360+/-133 cells/0.05 mm(2)neointima, P<0.001 vs control, respectively). In addition, balloon dilatation with the(32)P impregnated angioplasty catheter increased the vessel perimeter as compared to balloon dilatation with a non-impregnated catheter (4. 7+/-0.2 vs 3.9+/-0.3 mm, P<0.001 vs control).. Simultaneous balloon dilatation and vascular brachytherapy with a novel(32)P impregnated angioplasty catheter markedly reduces restenosis in vivo by preventing neointimal hyperplasia and constrictive vascular remodelling.

Topics: Angioplasty, Balloon; Animals; Arteriosclerosis; Beta Particles; Brachytherapy; Catheterization; Female; Hyperplasia; Iliac Artery; Models, Animal; Monte Carlo Method; Phosphorus Radioisotopes; Rabbits; Radiotherapy Dosage; Recurrence; Tunica Intima

The dose along the radial direction located at the midplane of a radioactive stent, simulated by a uniform cylinder of 32P, is represented by an analytical function consisting of the sum of two modified exponentials. This procedure reproduces values obtained from numerical integration, for which no closed form exists, to within 5% for distances up to 6 mm from the wall and for stent diameters from 2-6 mm.

Topics: Angioplasty; Animals; Arteriosclerosis; Biometry; Biophysical Phenomena; Biophysics; Humans; Muscle, Smooth, Vascular; Phosphorus Radioisotopes; Radiotherapy Dosage; Recurrence; Stents

Since somatic mutations are suspected to contribute to the pathogenesis not only of cancer but also of atherosclerotic plaques, we measured DNA adducts in the smooth muscle layer of atherosclerotic lesions in abdominal aorta specimens taken at surgery from seven patients. DNA adducts were evaluated in three laboratories by means of different molecular dosimetry methods, including: (a) HPLC/fluorescence, which specifically identifies the DNA adducts of the anti-benzo(a)pyrene (BPDE) isomer; (b) two- and three-dimensional synchronous fluorescence spectrophotometries, which detect DNA adducts of BPDE and other reactive metabolites of polycyclic aromatic hydrocarbons; and (c) 32P postlabeling, which reveals the presence of a variety of types of DNA adducts. The HPLC/fluorescence method provided for the first time evidence for the presence of BPDE-DNA specific adducts in three of six specimens tested. Synchronous fluorescence spectrophotometry displayed broad areas of fluorescence in all seven specimens, thereby suggesting the occurrence not only of BDPE-DNA but also of other DNA adducts with similar fluorescence characteristics. All specimens were also positive at 32P postlabeling, which revealed multiple spots detectable following enrichment either with nuclease P1 or butanol, indicative of the presence of different aromatic DNA adducts. Thus, the data obtained by applying typical cancer biomarkers provide further support to the hypothesis that there may be similarities between the carcinogenic and the atherogenic processes, and in particular that genetic alterations caused by DNA-binding agents in the artery wall may be detected in atherosclerotic lesions.

Topics: Aged; Aged, 80 and over; Aorta, Abdominal; Aortic Diseases; Arteriosclerosis; Benzo(a)pyrene; Biomarkers, Tumor; Butanols; Chromatography, High Pressure Liquid; DNA Adducts; Female; Fluorescence; Humans; Male; Middle Aged; Muscle, Smooth, Vascular; Phosphorus Radioisotopes; Polycyclic Compounds; Single-Strand Specific DNA and RNA Endonucleases; Spectrometry, Fluorescence

Our experiments aimed at the in vitro development of cells similar to macrophage foam cells of vessel wall. Fatty macrophages were produced by Intralipid incubation of peritoneal macrophages and their motility was studied in vivo. Our results showed that fat-saturated, isotope and colloid-gold marked macrophages can get through the vessel wall, so they are able to in vivo migration.

Topics: Animals; Arteriosclerosis; Cell Movement; Cells, Cultured; Cholesterol; Fat Emulsions, Intravenous; Humans; In Vitro Techniques; Lipoproteins, LDL; Macrophages; Peritoneum; Phosphorus Radioisotopes; Rats; Rats, Inbred Strains

Topics: Analysis of Variance; Animals; Aorta; Aortic Diseases; Arteriosclerosis; Autoanalysis; Blood Platelets; Carbon Radioisotopes; Catheterization; Cholesterol; Chromatography, Gas; Linoleic Acids; Lipid Metabolism; Oleic Acids; Phospholipids; Phosphorus Radioisotopes; Rabbits; Thrombosis

Topics: Animals; Arteriosclerosis; Autoradiography; Carbon Radioisotopes; Humans; Lipids; Phosphorus Radioisotopes

Topics: Adult; Arteriosclerosis; Cardiac Glycosides; Coronary Disease; Female; Humans; Male; Middle Aged; Phosphorus Radioisotopes; Potassium; Rheumatic Heart Disease; Scintillation Counting

Topics: Arteriosclerosis; Barbiturates; Blood; Chloramphenicol; Cholesterol; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Steroids