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Evaluation functional and inflammatory of lungs submitted to treatment hypertonic solution in model brain death


Lung transplantation when indicated for the treatment of advanced lung disease provides a better quality of life and survival. The care with donor for lungs preservation is essential for good pulmonary function after transplantation. The changes related to brain death affect the viability of organs for donation, because it compromise the cellular biochemistry and cause physiological and hemodynamic dysfunctions. These events cause imbalance of ventilation/perfusion and immune system activation, with increased IL-1b and IL-6 interleukins and tumor necrosis factor (TNF-a), potentiating the risk of lung injury during reperfusion of the organ. Hypertonic saline solution - 7.5% (HSS-7, 5%) has important immunomodulatory effect by inhibiting leukocyte activation and can be considered a pre-treatment for organ donors. This project aims to study the evolution of lung function, ventilatory mechanics; and inflammatory cascade during the first 6 hours after brain death in animals subjected to treatment with HSS-7,5%. This study will be conducted in the Medical Research Laboratories 11 and 61 LIM of the Faculty of Medicine, University of São Paulo (USP). Forty male Wistar rats weighing between 250 and 350 grams of the FMUSP biotery will be used. The animals will be anesthetized with 5% isoflurane in a closed chamber and subjected to orotracheal intubation for mechanical ventilation through flexiVent fan with 100% FiO2, tidal volume of 10 ml/kg and 70 cycles per minute. The animals will be submitted to trichotomy of the right lateral cervical region, median longitudinal dorsal and skull region with subsequent local antisepsis. The right carotid artery and the right jugular vein will be cannulated using PE-10 and PE-50 Clay Adams polyethylene catheters respectively. The artery catheter will be connected to a pressure transducer coupled to a multichannel system computerized data acquisition. The jugular vein is reserved for infusion of fluids. The rats will be divided into four groups: (1) False-operated: rats subjected to trepanning without brain death, (2) Control: rats injected with saline solution 0.9% (4 ml / kg) immediately after brain death, (3) 0h Hypertonic Saline Solution: rats treated with HSS-7,5% (4 mL / kg) immediately after brain death, (4) 1h Hypertonic Saline Solution: rats treated with HSS-7,5% (4 mL / kg) after 60 minutes of brain death. The animals will be subjected to trepanation and subsequent intracranial insertion of a 4F-Fogarty catheter. Brain death will be induced by rapid inflation of the catheter with saline solution and confirmed by a hypertensive peak, absence of reflexes, dilated pupils and apnea. Then anesthesia will be discontinued. Hemodynamic parameters, heart rate and mean arterial pressure will be monitored and recorded continuously. Compliance, elastance, and PV curve data will be provided by the fan Flexivent before and after brain death. Blood samples will be collected from the carotid artery for determination of pH, pO2, pCO2, sodium potásssio, calcium, chloride and lactate. Supernatant samples of the of lung tissue homogenate will be used for determining the cytokines concentration. Serum concentrations of TNF-±, IL-1², IL-6, IL-10 will be determined by enzyme immunoassay. Results will be expressed as mean ± standard error of the mean and analyzed by analysis of variance (ANOVA) followed by Tukey-Kramer test for multiple comparisons or, when appropriate, will be used nonparametric Kruskal-Wallis test followed by Dunn. The significance level will be 5% (p <0.05). (AU)

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