RESUMO
BACKGROUND: Ischemia-reperfusion injury may lead to insufficient microcirculation and results in partial flap loss during the free flap surgeries. OBJECTIVE: This study aimed to investigate the effect of trimetazidine (TMZ) on oxidative stress, inflammation and histopathological changes, using the epigastric skin flap model in rats. METHODS: 40 male Wistar rats were used, that were divided into four groups. Control group, non-treated ischemic (I/R)-group and two trimetazidine treated groups (preischemically, postischemically) were established. To create ischemia in the skin flap, the superficial epigastric vessels were clamped for six hours, followed by twenty-four hours of reperfusion. Blood samples and biopsies from skin flaps were collected at the end of the reperfusion period. The inflammatory response, the degree of oxidative stress (by measuring the plasma level of malondialdehyde (MDA), reduced glutathione (GSH); sulfhydryl (-SH) groups) and histopathological changes were evaluated. RESULTS: Inflammatory response, and oxidative stress were significantly attenuated in the trimetazidine treated groups, compared to the non-treated ischemic group. Histopathological findings were also correlated with the biochemical results. CONCLUSION: In our study trimetazidine could reduce the ischaemia-reperfusion injury, even after an unexpected ischemic period, so it is a promising drug during free tissue transfer, replantation or during revascularization procedures in the future.
Assuntos
Traumatismo por Reperfusão/tratamento farmacológico , Retalhos Cirúrgicos/transplante , Trimetazidina/uso terapêutico , Vasodilatadores/uso terapêutico , Animais , Masculino , Ratos , Ratos Wistar , Traumatismo por Reperfusão/patologia , Trimetazidina/administração & dosagem , Trimetazidina/farmacologia , Vasodilatadores/administração & dosagem , Vasodilatadores/farmacologiaRESUMO
AIMS: We studied the new anti-inflammatory effects of non-specific phosphodiesterase (PDE) inhibitor pentoxifylline (PTX) on ischaemia-reperfusion injury and postconditioning of the lower extremities. We aimed to examine the oxidative stress parameters (OSP), the inflammatory response and the changes in structure of skeletal muscle after revascularization surgery. METHODS: 50 Wistar rats in five groups underwent a 60âmin infrarenal aortic cross clamping. After the ischaemia in IR+PC group ischemic postconditioning was performed, intermittent 15 seconds reperfusion, 15 seconds ischaemic periods were applied four times. The ischemic phase was followed by a 120âmin of reperfusion. In IR+PTX group the animals were treated with PTX. In IR+PC+PTX group both ischemic postconditioning and PTX treatment were performed. Blood samples and biopsy from quadriceps muscle were collected. Plasma malondialdehyde, reduced glutathione, -SH-groups, TNF-alpha, IL-6 concentrations and superoxide dismutase enzyme activity were measured. RESULTS: The levels of OSP and the inflammatory proteins were significantly higher in the IR group. PTX treatment and PC could significantly decrease the levels of OSP and inflammatory proteins. When the animals were co-treated with PTX and PC the results were even better. CONCLUSIONS: Inhibition of PDE by PTX could markedly decrease the inflammatory response and moderate the ischaemia-reperfusion damages after lower limb ischemia and reperfusion. Administration of PTX could potentiate the beneficial effects of PC.