Protective effect of local temporary ischemia depends on applied dose of radiation.

The aim of this study was to verify hypothesis that protective effect of local temporary ischemia depends on dose of radiation. 56 male WAG-strain rats were used. Total body irradiation with 3 x 3 and 3 x 5 Gy was performed. Local temporary ischemia was induced by clamping the tail base. The biochemical parameters were the thiobarbituric acid-reactive substances (TBA-RS). In bone marrow smears the polychromatic erythrocyte (PCE) numbers were counted and the numbers of micronucleated PCEs were analyzed. In small intestines the numbers of crypts were calculated. The levels of TBA-RS in the serum of the animals irradiated with a 3 x 3 Gy dose were significantly different (P < 0.002). Also in animals irradiated with a dose of 3 x 3 Gy the numbers of intestinal crypts were different (P < 0.05). In animals irradiated with dose 3 x 5 Gy, for analyzed parameters differences did not achieve statistical significance. Local temporary ischaemia provides general protection against radiation damage for lower dose. This protective effect disappeared after applications of a higher dose of radiation.

[Radiotherapy as prevention of heterotopic ossification--preliminary results]. / Zastosowanie radioterapii jako metody zapobiegajacej kostnieniu pozakostnemu--doniesienie wstepne.

Heterotopic ossification is a common complication of hip arthroplasty (35-57%) and multifragmental acetabular fractures (50-70%). Due to complication level and cost of surgery in this region, more popular become methods of heterotopic ossification prevention as well as non-steroid anti inflammatory drug intake and radiotherapy (approximately 90% effectiveness in high risk groups). Presented material comprises 22 cases irradiated using a dose of 6-7 Gy delivered in one fraction to prevent ossification or to stop active process. No progress was found and only in one case secondary ossification appeared during follow up. Obtained results allow to form the conclusion that radiotherapy is easy, fast and cheap treatment modality giving good results without adverse effects.

Post-dilatation intravascular brachytherapy trials on hypercholesterolemic rabbits using 32P-phosphate solutions in angioplasty balloons.

PURPOSE: Response of peripheral arteries to post-dilatation intravascular brachytherapy (IVBT) using 32P liquid sources was studied in a rabbit model. METHODS: The applied sources were angioplasty balloons filled with aqueous solutions of Na2H32PO4, NaCl and iodinated contrast. Dose distribution was calibrated by thermoluminescence dosimetry. The uncertainty of in vitro determinations of the activity-dose dependence was +/- 15-30%. The animal experiments were performed on rabbits with induced hypercholesterolemia. The 32P sources were introduced into a randomly chosen (left or right) iliac artery, immediately after balloon injury. Due to the low specific activity of the applied sources, the estimated 7-49 Gy doses on the internal artery surface required 30-100 min irradiations. A symmetric, balloon-occluded but non-irradiated artery of the same animal served as control. Radiation effects were evaluated by comparing the thicknesses of various components of irradiated versus untreated artery walls of each animal. RESULTS: The treatment was well tolerated by the animals. The effects of various dose ranges could be distinguished although differences in individual biological reactions were large. Only the 49 Gy dose at "zero" distance (16 Gy at 1.0 mm from the balloon surface) reduced hypertrophy in every active layer of the artery wall. The cross-sectional intimal thicknesses after 7, 12, 38 and 49 Gy doses were 0.277, 0.219, 0.357 and 0.196 mm2 respectively, versus 0.114, 0.155, 0.421 and 0.256 mm2 in controls (p < 0.05). The lowest radiation dose on the intima induced the opposite effect. Edge intimal hyperplasia was not avoided, which agrees with other reports. The edge restenosis and the variability of individual response to identical treatment conditions must be considered as limitations of the post-dilatation IVBT method. CONCLUSION: Only application of highest irradiation doses was effective. The irradiation dose should be planned and calculated for adventitia.

32P liquid sources--comparison of the effectiveness of postangioplasty versus poststenting intravascular brachytherapy in hypercholesterolemic rabbits. Adjunctly implanted titanium stent does not attenuate the effect of endovascular irradiation.

PURPOSE: Endovascular application of ionizing radiation is a promising but still not sufficiently studied means of restenosis prevention. To test the effects of radiation on restenosis, and especially their dependence on whether the angioplasty was followed by stent implantation or not, we performed an in-stent versus no-stent intravascular brachytherapy study in an animal model. Balloon-based, continuous and self-centering, liquid 32P sources seemed the most convenient for the purpose. METHOD: The radial dose distribution around angioplasty balloons filled with solutions of Na(2)H32PO(4) was calibrated by thermoluminescence dosimetry, both in the absence and presence of stents. The animal experiments were performed on rabbits with induced hypercholesterolemia. The balloons containing 32P were introduced into iliac artery immediately after stent implantation or after angioplasty alone. Radiation effects were evaluated postmortem by comparing thickness of various components of the artery wall. RESULTS: In the presence of titanium stents (TTS), irradiation with 16 Gy dose at 1.0 mm from the balloon surface was no less effective in reducing hypertrophy in every active layer of the artery wall than without a stent. CONCLUSION: In the animal model, IVBT basing on P(32) liquid sources was no less effective in the stented arteries than in the nonstented ones.

[Interventional treatment of myocardial infarction. Own experience]. / Interwencyjne leczenie zawalu miesnia sercowego. Doswiadczenia wlasne.

UNLABELLED: The aim of the study is the analysis of own results of myocardial infarction treatment using percutaneous coronary intervention (PCI) in the setting of twenty-four hour long hemodynamic service. Between 01.12.1998 and 31.12.2001 249 patients with diagnosis of acute myocardial infarction were admitted to our Department. Their mean age was 58 years, men -73.5%, median of pain duration was 4 hours, diabetes occurred in 11.6%, hypertension in 37.3%, dyslipidemia occurred in 14%, smokers constituted 59% of patients. 60.2% of patients were in Killip class I, 18.5% in class II, 8.0% in class III and 13.3% in class IV. Anterior and/or lateral myocardial infarction was diagnosed in 105 patients, inferior and/or posterior in 144 patients. Angiography was performed in 225 patients, PCI was performed in 178. TIMI 3 flow was achieved in 76% of patients with shock and 90% of patients without shock. Multivessel coronary artery disease was present in 71% of patients. 30-day mortality in patients treated with PCI was 11.8%, after exclusion of III and IV Killip class patients mortality was 4.3%. 30-day mortality in group of patients with cardiogenic shock was 38.0%. Relative risk of death in patients in III and IV Killip class was higher for these treated conservatively: IV class -1.51 (p = 0.075), III and IV class (common group) -1.38 (p = 0.064). In the year of 2001 30-day mortality among the patients in I and II Killip class treated with PCI was 2.43%. CONCLUSIONS: 1. Primary percutaneous coronary intervention in the treatment of myocardial infarction improves prognosis in group of patients with cardiogenic shock in 30-day observation. 2. 11.8% mortality observed in our PCI treated group is associated in our opinion with occurrence of multivessel coronary disease in 71% of patients.

Endovascular gamma irradiation of the iliac arteries: 1-year results from a clinical safety and feasibility study.

PURPOSE: To estimate safety and feasibility of vascular brachytherapy in iliac arteries. METHODS: Fourteen patients (11 men; mean age 56.7+/-9.9 years, range 44-81) with occlusive disease in 15 iliac arteries (7 external, 8 common) were treated with balloon dilation followed by irradiation from an iridium 192 source (15 Gy at 3 mm from the inner surface of the artery wall) applied with a PARIS centering catheter and bilateral 10-mm margins. Patients receiving stents for suboptimal angioplasty were prescribed a 6-month course of antiplatelet treatment with ticlopidine. Angiography was routinely scheduled for 6 months after intervention. RESULTS: There were no complications of the angioplasty procedure or EVBT treatment; 7 patients received stents for dissection or residual stenosis. Mean follow-up was 12.4+/-6.0 months. At 6-month angiography, 1 (6.7%) restenosis in a common iliac artery stent was found. Another patient with a common iliac artery stent developed transient lower limb ischemia at 4 months, probably due to temporary suspension of antiplatelet treatment and distal disease. CONCLUSIONS: Brachytherapy in the iliac arteries appears to be feasible and safe; longer follow-up in more patients is needed to determine its clinical utility in the prevention of restenosis.

Lipid peroxidation and vitamin E in human coronary atherosclerotic lesions.

BACKGROUND: We aimed to assess the oxidant/antioxidant status within the ex vivo human coronary endarterectomy samples. METHODS: To achieve this, we measured products of lipid oxidation (malondialdehyde, 7-ketocholesterol), lipids (cholesterol, cholesteryl esters) and vitamin E in endarterectomy samples. RESULTS: Content of malondialdehyde in the plaque ranged from 0.23 to 37.36 microg/g. Unesterified cholesterol content ranged from 0.30 to 1.94 mg/g. It was 9.04+/-4.32% of total cholesterol. Total cholesterol content ranged from 1.73 to 23.69 mg/g. Cholesteryl palmitate content ranged from 0.57 to 19.10 mg/g, which is 11.43-60.86% of the total esters (mean+/-SD 40.27+/-18.42%). Cholesteryl oleate content ranged from 0.24 to 5.76 mg/g, being 9.97-21.81% of total esters (mean+/-SD 14.35+/-4.51%). Cholesteryl linoleate content ranged from 1.05 to 8.21 mg/g, being 17.84-45.15% of total esters (mean+/-SD 30.78+/-11.69%). Cholesteryl arachidonate content ranged from 0.51 to 4.20 mg/g, which is 7.56-22.87% of total esters (mean+/-SD 14.60+/-5.60%). The cholesteryl linoleate/cholesteryl oleate ratio (CL/CO) ranged from 1.01 to 4.33. Content of 7-ketocholesterol in the plaque ranged from 0.0 to 577.5 ng/g of wet weight. The 7-ketocholesterol/total cholesterol ratio was 0.003+/-0.003% (range from 0.0% to 0.008%). The 7-ketocholesterol/unesterified cholesterol ratio was 0.024+/-0.023% (range from 0.0% to 0.066%). The plaque content of vitamin E ranged from 0.0 to 40.9 microg/g of wet weight. CONCLUSION: The present study, comprising measurements of lipids, products of lipid peroxidation and vitamin E in 12 human coronary endarterectomy samples, lends the evidence for ongoing lipid peroxidation within an atherosclerotic lesion.

Inhibitory effect of local ischaemic preconditioning in total body irradiated rats.

The aim of this study was to explore the relationship between local ischaemic preconditioning and the effectiveness of fractionated radiotherapy. The rat serum, bone marrow, and small intestine were examined for oxidative changes induced by total body irradiation with gamma rays with applied local ischaemic preconditioning immediately before irradiation. Serum concentrations of TBA-RS examined 12 hours after the last irradiation did not reveal any differences among the groups of animals analyzed. Twenty-four hours after the last dose of irradiation, the serum concentrations of TBA-RS varied in particular groups (P<0.0001). The concentration of triglycerides in the serum of local preconditioned ischaemia and irradiated animals showed a reversed shape similar to the TBA-RS fluctuation (P<0.003). The level of uric acid in the serum of animals treated only with radiation is slightly higher than the level of this acid in the serum of the local preconditioned ischaemia radiation group (P<0.58). The number of bone marrow polychromatic erythrocytes did not appear to differ substantially in both irradiated groups. At the first 12 hours after irradiation, the frequency of micronucleated polychromatic erythrocytes is significantly different in the bone marrow of both groups either in combination with ischaemic preconditioned radiation or with radiation alone (P<0.0002). In irradiated animals without ischaemic preconditioning, on the 3rd day after irradiation the number of crypts increased and in the next days decreased achieving the level of the control group on the 7th day. Irradiated rats with local ischaemic preconditioning did not reveal an increase in the number of crypts. The difference was statistically significant (P<0.05). These data indicate that the local ischaemic preconditioning modifies the radiation peroxidising effects through inhibition of free radical-dependent lipid peroxidation and, probably, other unrecognized mechanisms.

Vascular brachytherapy after percutaneous transluminal angioplasty of superficial femoral arteries-Polish pilot group.

PURPOSE: The article presents the results of treatment with vascular brachytherapy (VBT) in superficial femoral arteries. This method aims to minimize frequency of restenosis after percutaneous transluminal angioplasty (PTA). METHOD: Treatment was carried out in 20 cases. The patients with severe stenoses or total occlusions verified in angiography were selected. In the group of 19 patients, two were women (the average age of the patients was 58.7 years). VBT was performed immediately after PTA. A 15-Gy dose, with high dose rate, was applied. The dose was calculated based on individually chosen distance from the internal surface of the artery wall, which varied from 2 to 3 mm. The mean observation time after treatment was 8 months. The shortest time was 1 month and the longest 14 months. At the end of the observation time, the control DSA angiography was performed on every patient. RESULTS: During the first 2 months, in three cases, an acute thrombosis in treated artery was observed. In the third month, one treated artery occluded. In the sixth month of observation, one case of acute thrombosis was observed. The rest of the patients were free of restenoses. CONCLUSIONS: (1) In superficial femoral arteries, a low value of ankle brachial pressure index (ABPI; below 0.4) is very probably responsible for acute thrombosis after PTA with or without stent implantation followed by VBT. (2) Diabetes, rest ischaemia before treatment, poor vessel status confirmed in angiography may also be responsible for acute thrombosis after VBT. (3) Anticoagulants or antiplatelet (ticlipidine) treatment must be ordered for 6 months after VBT in patients with implanted stents.

Post-stenting intravascular brachytherapy trials on hypercholesterolemic rabbits using 32P liquid sources: implications for prevention of in-stent restenosis.

PURPOSE: Liquid sources of radiation delivered in angioplasty balloons may be a convenient self-centering device used for prevention of in-stent restenosis. To test the effectiveness of this method an intravascular brachytherapy study was performed using 32P liquid sources in an animal model. METHODS: The radial dose distribution around angioplasty balloons filled with solutions of Na 2H 32PO 4 was calibrated by thermoluminescence dosimetry. The animal experiments were performed in rabbits with induced hypercholesterolemia. The balloons containing 32P were introduced into iliac arteries immediately after stent implantation. Estimated 7-49 Gy doses required 30-100 min irradiations. Radiation effects were evaluated by comparing the thickness of various components of the artery wall. RESULTS: Doses of 7, 12, 16 or 49 Gy on the internal artery surface required 30-100 min of irradiation. The dose of 49 Gy at "zero" distance corresponding to 16 Gy at 1.0 mm from the balloon surface reduced hypertrophy in every layer of the arterial wall: in the intima the cross-sectional areas were 0.13 versus 0.91 mm 2, in the media were 0.5 versus 0.46 mm 2 and in the adventitia were 0.04 versus 0.3 mm 2 (p <0.05). A dose of 7 Gy at the balloon surface produced adverse irradiation effects: the intimal area of the artery was 2.087 versus 0.857 mm 2, the medial area was 0.59 versus 0.282 mm 2 and the adventitial area was 0.033 versus 0.209 mm 2 in treated and control arteries, respectively. CONCLUSION: Application of a 49 Gy irradiation dose to the internal arterial surface effectively prevented in-stent restenosis.

[Regulation of intracellular processes by fatty acids and end products of lipid peroxidation]. / Regulacja procesów wewnatrzkomórkowych przez kwasy tluszczowe i koncowe produkty peroksydacji lipidów.

Products of ingested fat metabolism and also products of lipid peroxidation influenced on genes expression being natural ligands for nuclear receptors functioning as a transcription factors. This situation creates possibilities of diet modification by type and amount of fat as an important element of cancer prevention and cancer therapy. Functioning and activity of PPARs indicating the way of controlling their activity by another ligands than that included in the diet. This is a base for pharmacologic synthesis of a new class of specific drugs as an agonists for nuclear receptors of precisely defined histologic type of cancer.