RESUMO
BACKGROUND: In-stent restenosis and poor re-endothelization usually follow percutaneous transluminal coronary angioplasty, even using drug-eluting stents, due to inflammation and oxidative stress. Medical ozone has antioxidant and anti-inflammatory properties and has not been evaluated in this context. OBJECTIVES: To evaluate whether ozonotherapy might reduce restenosis following bare metal stents implantation in relation to the redoxin system in pigs. METHODS: Twelve male Landrace pigs (51±9kg) underwent percutaneous transluminal circumflex coronary arteries bare metal stent implantation under heparine infusion and fluoroscopical guidance, using standard techniques. Pigs were randomized to ozonetherapy (n=6) or placebo (n=6) treatment. Before stenting (24h) and twice a week for 30days post-stenting, venous blood was collected, ozonized and reinfused. Same procedure was performed in placebo group except for ozonation. Both groups received antiplatelet treatment. Histopathology and immunohistochemistry studies were performed. RESULTS: Severe inflammatory reaction and restenosis with increase in the immunohistochemical expression of thioredoxin-1 were observed in placebo group 30days after surgery. Oppositely, ozonetherapy drastically reduced inflammatory reaction and restenosis, and showed no increase in the Trx-1 immunohistochemical expression 30days after surgery. Immunolabeling for Prx-2 was negative in both groups. Ozonated autohemotherapy strikingly reduced restenosis 30days following PTCA with BMS implantation in pigs. CONCLUSIONS: Stimulation of the redoxin system by ozone pretreatment might neutralize oxidative damage from the start and increase antioxidative buffering capacity post-injury, reducing further damage and so the demand for antioxidant enzymes. Our interpretation agrees with the ozone oxidative preconditioning mechanism, extensively investigated.
Assuntos
Neointima/sangue , Neointima/prevenção & controle , Ozônio/administração & dosagem , Stents/efeitos adversos , Tiorredoxinas/sangue , Animais , Reestenose Coronária/sangue , Reestenose Coronária/etiologia , Reestenose Coronária/prevenção & controle , Masculino , Neointima/etiologia , Estudos Prospectivos , Distribuição Aleatória , Método Simples-Cego , SuínosRESUMO
Supplementation with antioxidants and its benefit-risk relationship have been largely discussed in the elderly population. We evaluated whether antioxidants supplementation improved the biochemical profile associated with oxidative metabolism in elderly cardiovascular patients. Patients (n = 112) received daily supplementation with α-TP 400 mg, beta-carotene 40 mg, and vitamin C 1000 mg for 2 months (treatment). Plasma concentrations of alpha-tocopherol (α-TP), ß-carotene (ßC), ubiquinol-10 (QH-10), glutathione, and thiobarbituric acid reactive substances (TBARS) were determined before and after treatment. Response to treatment was dependent on pretreatment α-TP and ßC levels. Increase in α-TP and ßC levels was observed only in patients with basal levels <18 µM for α-TP (P < 0.01) and <0.30 µM for ßC (P < 0.02). Ubiquinol-10, glutathione, and TBARS were unaffected by treatment: QH-10 (+57%, F(1,110) = 3.611, P < 0.06, and N.S.), glutathione (+21%, F(1,110) = 2.92, P < 0.09, and N.S.), and TBARS (-29%, F(1,110) = 2.26, P < 0.14, and N.S.). Treatment reduced oxidative metabolism: 5.3% versus 14.6% basal value (F(1,110) = 9.21, P < 0.0003). Basal TBARS/α-TP ratio was higher in smokers compared to nonsmokers: 0.11 ± 0.02 versus 0.06 ± 0.01 (F(32,80) = 1.63, P < 0.04). Response to antioxidant supplementation was dependent on basal plasma levels of α-TP and ßC. Smoking status was strongly associated with atherosclerotic cardiovascular disease and high TBARS/α-TP ratio (lipid peroxidation).