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Comparison between the prone position and supine position, associated with high frequency oscillatory ventilation (HFOV), on the oxidative stress and histopathological injury in model of acute lung injury (ALI) induced in rabbits.

Grant number: 11/00542-2
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): April 01, 2011
Effective date (End): March 31, 2012
Field of knowledge:Health Sciences - Medicine - Maternal and Child Health
Principal Investigator:Mário Ferreira Carpi
Grantee:Fábio Peres da Mota
Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil


Introduction: The Acute Lung Injury (ALI) is characterized by an inflammatory process that leads to disruption of the alveolar-capillary barrier to development of interstitial and alveolar edema, decreased lung compliance, pulmonary hypertension, imbalance of the ventilation / perfusion and hypoxemia refractory to oxygen, and its more severe form of the Acute Respiratory Distress Syndrome (ARDS). Mechanical ventilation (MV) is one of the mainstays of treatment of ALI / ARDS, is capable of modifying disease progression. A high frequency oscillatory ventilation (HFOV) are ventilatory method utilizing lower tidal volume than the volume of anatomical dead space, with frequencies well above the physiological, avoiding the high pressure and alveolar volumes typically conventional-ventilation. Due to the high mortality in ALI / ARDS, other therapeutic strategies, in addition to MV, have been developed, highlighting the prone position. The prone position can improve gas exchange for several reasons: 1) redistribution of ventilation to dorsal lung areas better perfused, with improvement of ventilation / perfusion ratio in these regions, 2) homogenization of the distribution of tidal volume, 3) alveolar recruitment, 4) redirection of compressive forces exerted by the weight of the heart on the lungs and 5) facilitating the removal of secretions. Considering the characteristics of HFOV and protective capacity of redistribution of ventilation to perfused lung areas better, and the potential recruitment of the prone position, our hypothesis is that the sum of beneficial effects of HFOV and prone positioning determines greatest improvement in oxidative stress and pathological lung compared with HFOV and supine position in an experimental model of ALI induced in rabbits. Objectives: The aim of the study will investigate the effect of the prone position associated with HFOV on oxidative stress and pulmonary histology, comparing it with the supine position also in this mode of ventilation in an experimental model of ALI induced in rabbits. Methods: Thirty rabbits will be instrumented and randomly selected to compose two groups: 1) animals with ALI undergoing HFOV in supine position (VAFS n = 15), 2) animals with ALI undergoing HFOV in prone position (VAFP n = 15 ). The LPA will be induced by repeated lung lavage with saline solution heated to 38oC in aliquots of 30 mL / kg to a maximum pressure of 30 cmH2O. The animals will be placed on HFOV after induction of ALI, and then placed in the prone position or kept in the supine position. Inicialmnte be ventilated with mean airway pressure (MAP) of 16 cmH2O and every 30 minutes MAP is lowered successively to 14, 12 and 10 cmH2O. After 2 hours, all animals will be relocated in the supine position and kept there for over 30 minutes. During the 150 minutes of experiment, the animals will be monitored closely in terms of ventilation and hemodynamic stability. The pulmonary histological damage will be quantified by a scoring system that analyzes seven variables (alveolar inflammation, interstitial inflammation, alveolar hemorrhage, interstitial hemorrhage, edema, atelectasis, and necrosis) with five individual degrees of severity for each. Oxidative stress in lung tissue sample will be evaluated by measurement of Malondialdehyde (MDA) by colorimetric method, using TBARS Assay Kit (Cayman Chemical Company, Ann Arbor, MI, USA). For all statistical tests will be used significance level of 5%.

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