Estudo dos efeitos oxidantes da ventila??o mec?nica em diferentes modos ventilat?rios sobre a resposta inflamat?ria pulmonar e sist?mica em ratos Wistar e humanos adultos.

Programa de P?s-Gradua??o em Sa?de e Nutri??o. Escola de Nutri??o, Universidade Federal de Ouro Preto.A Ventila??o Mec?nica (VM) tem como objetivo manter uma troca gasosa adequada no tratamento do paciente cr?tico. Todavia, a VM pode induzir processos inflamat?rios e ao desequil?brio redox devido aos seus efeitos antifisiol?gicos no sistema respirat?rio, bem como em outros ?rg?os e sistemas do corpo humano. Objetivos: O presente estudo analisou os efeitos oxidantes da VM nos modos ventila??o controlada a volume (VCV) e ventila??o controlada a press?o (VCP) em ratos wistar; assisto-controlado ? volume (ACV) e assisto-controlado a press?o (ACP) em humanos adultos sobre a resposta inflamat?ria pulmonar e sist?mica. Metodologia: o projeto foi composto por dois estudos: Estudo 1 (realizado em animais), f?meas Wistar adultas, foram divididas em tr?s grupos: controle (GC), ventila??o controlada a press?o (GVCP) e ventila??o controlada a volume (GVCV). Ap?s a realiza??o do protocolo experimental, os animais foram eutanasiados e, ent?o foi coletado o lavado broncoalveolar (LBA), o sangue e o tecido pulmonar para as an?lises morfom?tricas e bioqu?micas. Para realiza??o do Estudo 2 (realizado em humanos) foram utilizados pacientes, de ambos os sexos, com faixa et?ria entre 18 e 90 anos, que estavam sob ventila??o mec?nica, nas primeiras 24 h ap?s intuba??o orotraqueal, sendo divididos de forma randomizada em dois grupos experimentais, modo assisto-controlado ? volume (ACV) e modo assisto-controlado a press?o (ACP). Realizado o protocolo experimental, foram coletados o aspirado traqueal, o soro e os par?metros ventilat?rios dos pacientes. Resultados: No estudo 1, n?o houve diferen?a no n?mero de leuc?citos totais no LBA entre os grupos experimentais, entretanto, entre os subtipos celulares analisados foi observado maior influxo de linf?citos e neutr?filos no GVCV e GVCP em rela??o ao GC. Houve um aumento das atividades das enzimas SOD, catalase e MPO no GVCP comparado ao GC no par?nquima pulmonar. Em rela??o ao dano tecidual, foi observado maiores ?ndices tanto na peroxida??o lip?dica avaliado pelo TBARS quanto na oxida??o de prote?nas, avaliado pela prote?na carbonilada no GVCP comparado ao GC. Quanto aos biomarcadores inflamat?rios analisados, as quimiocinas CCL3 e CCL5 estiveram aumentadas nos dois grupos sob VM comparados ao GC. Em rela??o ?s an?lises estereol?gicas do par?nquima pulmonar foi observado redu??o na densidade de volume de espa?os a?reos alveolares e aumento na densidade de volume dos septos alveolares no GVCP quando comparado ao GC. No estudo 2, foram recrutados 15 pacientes, sendo 9 pacientes do sexo masculino e 6 feminino, o Escore de RASS variou entre -4 e -5, os modos ventilat?rios foram escolhidos randomicamente de forma que ficaram 9 no modo ACP e 6 no ACV, com PEEP entre 5 a 7 cm H2O, FiO2 entre 28 a 40%, FR: 12-18 irpm. Na avali??o do influxo leucocit?rio no aspirado traqueal, foi observado um maior n?mero de neutr?filos no ACP quando comparado ao ACV. As an?lises bioqu?micas revelaram maior atividade da catalase no grupo ACP, no entanto houve maior peroxida??o lip?dica e oxida??o de prote?nas no modo ACV quando comparado ao ACP. Em rela??o aos biomarcadores inflamat?rios no aspirado traqueal, os n?veis de IL-6, IL-8, IL-33 e TNF-? foram maiores no modo ACV quando comparado ao modo ACP. Conclus?o: No estudo 1, o modo controlado a press?o promoveu altera??es estruturais no par?nquima pulmonar, bem como um maior desquil?brio redox em animais adultos saud?veis submetidos a ventila??o mec?nica. No estudo 2, nossos resultados demonstraram que modo ACV levou a um influxo de neutr?filos e ao dano oxidativo pulmonar em humanos submetidos a ventila??o mec?nica.Mechanical ventilation (MV) aims to maintain an adequate gas exchange in the treatment of critically ill patients. However, MV may induce inflammatory processes and redox imbalance due to its anti-physiological effects on the respiratory system as well as on other organs and systems of the human body. Objectives: The present study analyzed the oxidative effects of MV in volume-controlled ventilation (VCV) and pressure-controlled ventilation (PCV) modes in Wistar rats; assist volume-controlled (AVC) and assist pressure-controlled (APC) modes in adult humans in the pulmonary and systemic inflammatory response. Methodology: The project consisted of two studies: Study 1 (performed on animals), adult Wistar females were divided into three groups: control (CG), pressure-controlled ventilation (PCVG), and volume-controlled ventilation (VCVG). After the experimental protocol was performed, the animals were euthanized, and the bronchoalveolar lavage (BAL), blood and lung tissue were collected for morphometric and biochemical analyzes. In order to perform Study 2 (assessed in humans), patients of both sexes, between the ages of 18 and 90 years, who were under mechanical ventilation, for the first 24 h after orotracheal intubation, and were randomly divided into two experimental groups, assist volume-controlled (AVC) and assist pressure-controlled (APC) modes. At the end of the experimental protocol, tracheal aspirate, serum, and ventilatory parameters were collected from the patients. Results: In study 1, there was no difference in the number of total BAL leukocytes between the experimental groups, however, between the cell subtypes analyzed, there was a greater influx of lymphocytes and neutrophils in VCVG and PCVG compared to CG. There was an increase in the activities of the enzymes SOD, catalase, and MPO in PCVG compared to CG in the pulmonary parenchyma. Regarding tissue damage, higher rates were observed in the lipid peroxidation evaluated by TBARS as well as in protein oxidation, evaluated by carbonated protein in PCVG compared to CG. The inflammatory markers, CCL3 and CCL5 chemokines, increased in both groups under MV compared to CG. Regarding the stereological analysis of the pulmonary parenchyma, a reduction in the volume density of the alveolar airspace and an increase in the volume density of the alveolar septa in PCVG were observed when compared to CG. In study 2, 15 patients were enrolled, 9 men and 6 women, the RASS score ranged from -4 to -5, the ventilatory modes were randomly chosen so that 9 were in APC mode and 6 were in AVC mode, with PEEP between 5 to 7 cm H2O, FiO2 between 28 to 40%, RR: 12-18 bpm. While evaluating the leukocyte influx in tracheal aspirate, a higher number of neutrophils were observed in APC compared to AVC. Biochemical analyses showed a higher catalase activity in APC compared to AVC group. However, there was a significant lipid peroxidation and protein oxidation in the AVC mode when compared to the APC mode. Regarding the inflammatory biomarkers in tracheal aspirate, IL-6, IL-8, IL-33, and TNF-? levels were higher in AVC when compared to APC mode. Conclusion: In study 1, the pressure-controlled ventilation mode promoted structural changes in the lung parenchyma, as well as a more significant redox imbalance in healthy adult animals submitted to mechanical ventilation. In study 2, our results demonstrated that AVC increased the neutrophil influx and pulmonary oxidative damage in mechanically ventilated humans