Wodniecki J

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.

Neopterin and Beta-2 Microglobulin Relations to Immunity and Inflammatory Status in Nonischemic Dilated Cardiomyopathy Patients

Background. The aim of the study was to assess the relationships among serum neopterin (NPT), β2-microglobulin (β2-M) levels, clinical status, and endomyocardial biopsy results of dilated cardiomyopathy patients (DCM). Methods. Serum NPT and β-2 M were determined in 172 nonischaemic DCM patients who underwent right ventricular endomyocardial biopsy and 30 healthy subjects (ELISA test). The cryostat biopsy specimens were assessed using histology, immunohistology, and immunochemistry methods (HLA ABC, HLA DR expression, CD3 + lymphocytes, and macrophages counts). Results. The strong increase of HLA ABC or HLA DR expression was detected in 27.2% patients—group A—being low in 72.8% patients—group B. Neopterin level was increased in patients in group A compared to healthy controls 8.11 (4.50–12.57) versus 4.99 (2.66–8.28) nmol/L (P < 0.05). β-2 microglobulin level was higher in DCM groups A (2.60 (1.71–3.58)) and B (2.52 (1.51–3.72)) than in the control group 1.75 (1.28–1.96) mg/L, P < 0.001. Neopterin correlated positively with the number of macrophages in biopsy specimens (P < 0.05) acute phase proteins: C-reactive proteins (P < 0.05); fibrinogen (P < 0.01); and NYHA functional class (P < 0.05) and negatively with left ventricular ejection fraction (P < 0.05). Conclusions. Neopterin but not β-2 microglobulin concentration reflected immune response in biopsy specimens. Neopterin correlated with acute phase proteins and stage of heart failure and may indicate a general immune and inflammatory activation in heart failure.

Response to Inhaled Nitric Oxide, But neither Sodium Nitroprusside nor Sildenafil, Predicts Survival in Patients with Dilated Cardiomyopathy Complicated with Pulmonary Hypertension

Introduction: Pulmonary hypertension in patients with dilated cardiomyopathy is associated with higher mortality. Objectives: The aim of the study was to assess the predictive value of the vasodilator response to three different drugs, sodium nitroprusside, inhaled nitric oxide, and oral sildenafil, in patients with dilated cardiomyopathy complicated with pulmonary hypertension. Patients and methods: Twenty-nine patients with dilated cardiomyopathy complicated with postcapillary pulmonary hypertension (left ventricle ejection fraction (LVEF) 20.6 ± 8.2%, mean pulmonary artery pressure (mPAP) 42.49 ± 7.27 mmHg, transpulmonary gradient (TPG)>12 mmHg or pulmonary vascular resistance index (PVRI)>5 WU/m2) underwent single-session vaso reactivity testing with sodium nitroprusside, inhaled nitric oxide (120 ppm), oral sildenafil (50 mg), and a combination of sildenafil and inhaled nitric oxide. The vasodilator responders were defined as those participants who achieved a reduction of PVRI<5 WU/m2 and TPG<12 mmHg. The primary study endpoint was death in the 30-month-long follow-up. Kaplan-Meier analysis and Cox proportional hazard modelling were used to identify the predictors of survival. Results: In the follow-up, eight patients died (six patients with irreversible pulmonary hypertension). Six patients underwent successful heart transplantation. Multivariate Cox proportional hazard analysis disclosed a response to nitric oxide as the only predictor of longer survival (HR=11.77, 95% CI=1.12-123.9 at P=0.04). Conclusions: Vasodilator response to inhaled nitric oxide predicts longer survival in patients with dilated cardiomyopathy complicated with pulmonary hypertension.

Post-Dilatation Intravascular Brachytherapy Trials on Hypercholesterolemic Rabbits Using 32P-Phosphate Solutions in Angioplasty Balloons

Abstract Response of peripheral arteries to post-dilatation intravascular brachytherapy (IVBT) using 32P liquid sources was studied in a rabbit model. 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. 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. 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.