O organismo apresenta diversas reações integradas em resposta à injúria, com o objetivo de restaurar a homeostase. Dentre esses mecanismos, destaca-se a resposta inflamatória, já que sem ela a injúria que acometeu o organismo dificilmente seria resolvida. Todo procedimento cirúrgico representa uma injúria para o organismo. As técnicas cirúrgicas minimamente invasivas tendem a gerar respostas deletérias mais brandas aos animais; as cirurgias torácicas envolvem, porém, um trauma adicional caracterizado pelo colapso pulmonar, que se faz necessário mesmo nas técnicas minimamente invasivas. Foram realizados em humanos diversos estudos que avaliam as vantagens desta técnica em relação à toracotomia; na espécie eqüina, a toracoscopia vem sendo aplicada na rotina hospitalar desde a década de 80 e relatos afirmam ser um procedimento cirúrgico seguro. No entanto, não foram descritos dados referentes à resposta inflamatória decorrente deste procedimento. Desta forma, este estudo visou avaliar a resposta inflamatória sistêmica e local decorrente da técnica, na qual a indução e redução do colapso pulmonar foram feitas de maneira controlada. Foram utilizados 12 eqüinos hígidos, de raça e idade variadas, de ambos os sexos. Os animais foram divididos em dois grupos, submetidos à toracoscopia com duração de 30 e 60 minutos (grupos 1 e 2, respectivamente). As pressões intratorácicas foram controladas em todos os procedimentos, permitindo controle da indução e redução do colapso pulmonar, diminuindo assim a ocorrência de pneumotórax residual. Amostras de sangue, líquido pleural e lavado bronco alveolar foram coletadas antes do procedimento (M1), e duas (M6), seis (M7) e 24 horas (M8) após o início do colapso pulmonar. Estas foram usadas para avaliação da resposta inflamatória por meio de mensuração da produção de espécies reativas de oxigênio (ERO) pelas células presentes em cada tipo de amostra, utilizando-se como metodologia a citometria de fluxo, e para a quantificação de citocinas por ELISA (IL-1β) ou por ensaio biológico (TNF-α e IL-6). Para análise dos resultados foi considerada a possível influência dos fatores grupo e momento experimental em cada uma das variáveis estudadas. Os valores de burst oxidativo apresentados pelas células das amostras em questão não sofreram influência dos fatores avaliados. Não foi possível avaliar a variação dos níveis de IL-1β pela metodologia aplicada. Os níveis de TNF-α sofreram influência estatisticamente significativa do fator momento experimental nas amostras de lavado broncoalveolar e líquido pleural, sendo que M6 apresentou maiores níveis desta citocina; não foi observada influência desses fatores nos níveis plasmáticos da mesma. Em relação a IL-6, foi observada influência do fator momento experimental nas amostras de plasma e lavado broncoalveolar, e de ambos os fatores nas amostras de líquido pleural, sendo que os níveis dessa citocina apresentaram um padrão de aumento mais tardio que o apresentado pelo TNF-α. Concluímos que o colapso pulmonar induzido por infusão de gás CO2 em eqüinos hígidos provocou uma reação inflamatória localizada na cavidade torácica, em que não foram observadas diferenças significativas entre os dois grupos experimentais. Assim, a cirurgia torácica videoassistida em eqüinos com até 60 minutos de duração pode ser indicado sem que fatores oriundos da técnica cirúrgica agravem a enfermidade. Uma vez que não foi observada influência dos fatores estudados nos valores de pressão intratorácica, acreditamos que a metodologia aplicada foi adequada para a realização da técnica, provendo adequado controle e redução da ocorrência de pneumotórax residual, que somente foi observado nos casos onde ocorreu pneumotórax bilateral durante o procedimento cirúrgico. / Organisms present several integrative reactions to injury, aiming at the reestablishment of homeostasis. Among these mechanisms is the inflammatory reaction, for without it the initial injury would hardly be solved. Every surgical procedure represents an injury for living organisms. Minimally invasive surgical techniques tend to induce milder negative reactions in animals; nonetheless, thoracic surgery leads to an additional trauma characterized by lung collapse, required even in minimally invasive surgical techniques. Several human studies have assessed the advantages of this technique compared to thoracotomy; in horses, the use of thoracoscopy has increased in routine procedures since the 1980s, and reports point to the safety of its usage. Nevertheless, no data regarding the inflammatory reaction induced by this procedure has been reported. In this matter, our study aimed at the evaluation the local and systemic inflammatory response associated with this technique, in which the induction and reduction of lung collapse were carefully controlled. 12 healthy horses of varied breeds, age, and of both genders were used. Animals were divided in two groups, and submitted to thoracoscopy for 30 or 60 minutes (groups 1 and 2, respectively). Intrathoracic pressure was controlled in every procedure, allowing the induction and reduction of lung collapse, reducing the chance of residual pneumothorax. Samples of blood, pleural fluid, and bronchoalveolar fluid were harvested before the procedure (M1), and two (M6), six (M7) and twenty-four hours (M8) after the onset of lung collapse. These samples were employed for the evaluation of the inflammatory reaction through measurement of reactive oxygen species (ROS) by cells present in each sample, using flow cytometry, and for cytokine quantification by ELISA (IL-1β) or bioassay (TNF-α and IL-6). For the analysis of our results the factors group and experimental timepoint were considered for every variable studied. Values of oxidative burst displayed by cells in each sample did not depend on the factors analyzed. Variation of IL-1β levels could not be detected by the methods employed here. Levels of TNF-α were statistically influenced by the factor experimental timepoint in pleural fluid and bronchoalvolar fluid, and the highest levels of this cytokine were observed in M6; no influence of these factors on its plasmatic levels was observed. Regarding IL-6, we found an influence of the factor timepoint in samples of plasma and bronchoalveolar fluid, and an influence of both factors in samples of pleural fluid, being the highest levels of this cytokine found later than the TNF-α peak. We conclude that the lung collapse induced by CO2 in healthy horses caused an inflammatory reaction restricted to the thoracic cavity, without significant differences between groups 1 and 2. Thus, video-assisted thoracic surgery in horses lasting up to 60 minutes can be recommended leads to no signs of direct negative effects of the technique that could worsen the patient condition. Since we found no influence of either factor studied on values of thoracic pressure, we conclude that the methods employed for the surgery were adequate, supplying sufficient control over the occurrence of residual pneumothorax, observed only in cases of bilateral pneumothorax during the procedure.

O organismo apresenta diversas reações integradas em resposta à injúria, com o objetivo de restaurar a homeostase. Dentre esses mecanismos, destaca-se a resposta inflamatória, já que sem ela a injúria que acometeu o organismo dificilmente seria resolvida. Todo procedimento cirúrgico representa uma injúria para o organismo. As técnicas cirúrgicas minimamente invasivas tendem a gerar respostas deletérias mais brandas aos animais; as cirurgias torácicas envolvem, porém, um trauma adicional caracterizado pelo colapso pulmonar, que se faz necessário mesmo nas técnicas minimamente invasivas. Foram realizados em humanos diversos estudos que avaliam as vantagens desta técnica em relação à toracotomia; na espécie eqüina, a toracoscopia vem sendo aplicada na rotina hospitalar desde a década de 80 e relatos afirmam ser um procedimento cirúrgico seguro. No entanto, não foram descritos dados referentes à resposta inflamatória decorrente deste procedimento. Desta forma, este estudo visou avaliar a resposta inflamatória sistêmica e local decorrente da técnica, na qual a indução e redução do colapso pulmonar foram feitas de maneira controlada. Foram utilizados 12 eqüinos hígidos, de raça e idade variadas, de ambos os sexos. Os animais foram divididos em dois grupos, submetidos à toracoscopia com duração de 30 e 60 minutos (grupos 1 e 2, respectivamente). As pressões intratorácicas foram controladas em todos os procedimentos, permitindo controle da indução e redução do colapso pulmonar, diminuindo assim a ocorrência de pneumotórax residual. Amostras de sangue, líquido pleural e lavado bronco alveolar foram coletadas antes do procedimento (M1), e duas (M6), seis (M7) e 24 horas (M8) após o início do colapso pulmonar. Estas foram usadas para avaliação da resposta inflamatória por meio de mensuração da produção de espécies reativas de oxigênio (ERO) pelas células presentes em cada tipo de amostra, utilizando-se como metodologia a citometria de fluxo, e para a quantificação de citocinas por ELISA (IL-1β) ou por ensaio biológico (TNF-α e IL-6). Para análise dos resultados foi considerada a possível influência dos fatores grupo e momento experimental em cada uma das variáveis estudadas. Os valores de burst oxidativo apresentados pelas células das amostras em questão não sofreram influência dos fatores avaliados. Não foi possível avaliar a variação dos níveis de IL-1β pela metodologia aplicada. Os níveis de TNF-α sofreram influência estatisticamente significativa do fator momento experimental nas amostras de lavado broncoalveolar e líquido pleural, sendo que M6 apresentou maiores níveis desta citocina; não foi observada influência desses fatores nos níveis plasmáticos da mesma. Em relação a IL-6, foi observada influência do fator momento experimental nas amostras de plasma e lavado broncoalveolar, e de ambos os fatores nas amostras de líquido pleural, sendo que os níveis dessa citocina apresentaram um padrão de aumento mais tardio que o apresentado pelo TNF-α. Concluímos que o colapso pulmonar induzido por infusão de gás CO2 em eqüinos hígidos provocou uma reação inflamatória localizada na cavidade torácica, em que não foram observadas diferenças significativas entre os dois grupos experimentais. Assim, a cirurgia torácica videoassistida em eqüinos com até 60 minutos de duração pode ser indicado sem que fatores oriundos da técnica cirúrgica agravem a enfermidade. Uma vez que não foi observada influência dos fatores estudados nos valores de pressão intratorácica, acreditamos que a metodologia aplicada foi adequada para a realização da técnica, provendo adequado controle e redução da ocorrência de pneumotórax residual, que somente foi observado nos casos onde ocorreu pneumotórax bilateral durante o procedimento cirúrgico. / Organisms present several integrative reactions to injury, aiming at the reestablishment of homeostasis. Among these mechanisms is the inflammatory reaction, for without it the initial injury would hardly be solved. Every surgical procedure represents an injury for living organisms. Minimally invasive surgical techniques tend to induce milder negative reactions in animals; nonetheless, thoracic surgery leads to an additional trauma characterized by lung collapse, required even in minimally invasive surgical techniques. Several human studies have assessed the advantages of this technique compared to thoracotomy; in horses, the use of thoracoscopy has increased in routine procedures since the 1980s, and reports point to the safety of its usage. Nevertheless, no data regarding the inflammatory reaction induced by this procedure has been reported. In this matter, our study aimed at the evaluation the local and systemic inflammatory response associated with this technique, in which the induction and reduction of lung collapse were carefully controlled. 12 healthy horses of varied breeds, age, and of both genders were used. Animals were divided in two groups, and submitted to thoracoscopy for 30 or 60 minutes (groups 1 and 2, respectively). Intrathoracic pressure was controlled in every procedure, allowing the induction and reduction of lung collapse, reducing the chance of residual pneumothorax. Samples of blood, pleural fluid, and bronchoalveolar fluid were harvested before the procedure (M1), and two (M6), six (M7) and twenty-four hours (M8) after the onset of lung collapse. These samples were employed for the evaluation of the inflammatory reaction through measurement of reactive oxygen species (ROS) by cells present in each sample, using flow cytometry, and for cytokine quantification by ELISA (IL-1β) or bioassay (TNF-α and IL-6). For the analysis of our results the factors group and experimental timepoint were considered for every variable studied. Values of oxidative burst displayed by cells in each sample did not depend on the factors analyzed. Variation of IL-1β levels could not be detected by the methods employed here. Levels of TNF-α were statistically influenced by the factor experimental timepoint in pleural fluid and bronchoalvolar fluid, and the highest levels of this cytokine were observed in M6; no influence of these factors on its plasmatic levels was observed. Regarding IL-6, we found an influence of the factor timepoint in samples of plasma and bronchoalveolar fluid, and an influence of both factors in samples of pleural fluid, being the highest levels of this cytokine found later than the TNF-α peak. We conclude that the lung collapse induced by CO2 in healthy horses caused an inflammatory reaction restricted to the thoracic cavity, without significant differences between groups 1 and 2. Thus, video-assisted thoracic surgery in horses lasting up to 60 minutes can be recommended leads to no signs of direct negative effects of the technique that could worsen the patient condition. Since we found no influence of either factor studied on values of thoracic pressure, we conclude that the methods employed for the surgery were adequate, supplying sufficient control over the occurrence of residual pneumothorax, observed only in cases of bilateral pneumothorax during the procedure.

Critical care patients are often connected to ventilators, to support or replace their breathing. The ventilators deliver a mixture of gas to the patient by applying a specific volume or pressure, and then the patient exhales passively. This thesis is based of the hypothesis that a slower reduction of the expiration pressure could benefit intensive care patients connected to a ventilator. To enable research within the area, a device which can control the expiration is needed. In this thesis project, an expiration valve was controlled to create different pressure patterns during expiration. To facilitate the research and the usage of the expiration control, an application software was created with the purpose to simulate relevant pressure, flow and volume curves. The prototype is an expiration cassette created for the ventilator Servo-i by Maquet Getinge Group. To enable flexibility, the prototype is external and no information is transmitted from or to the ventilator. The prototype has its own flow and pressure sensors. The different pressure patterns which the prototype uses are designed as a linear decrease and as if a constant resistance was added to the system. The user can also create their own pressure pattern, by deciding 20 pressure points in the duration of two seconds. The simulation application was designed with the ability to simulate the same pressure patterns available with the prototype. By using a lung model, it is possible to simulate the ideal pressure, flow and volume in the lungs which can be expected from the chosen expiration control. During the implementation, two different types of lung models were evaluated in order to determine the specificity required. The prototype was tested with settings which were chosen to challenge the performance of the control. Some problematic areas were detected, such as high pressures or large volumes. However, the prototype was judged to perform well enough to be used in animal trials. The lung model used for the simulation application was a simple model of the lung, consisting of a resistor and a capacitor in series. The simulations were compared with the real system with the purpose to get an indication on the difference between theory and reality. The application presents the expected behavior when using the expiration control. However, it should be kept in mind by the user that the application represents a theoretical model.

Background: Atelectasis can provoke pulmonary and non-pulmonary complications after general anaesthesia. Unfortunately, there is no instrument to estimate atelectasis and prompt changes of mechanical ventilation during general anaesthesia. Although arterial partial pressure of oxygen (PaO2) and intrapulmonary shunt have both been suggested to correlate with atelectasis, studies yielded inconsistent results. Therefore, we investigated these correlations. Methods: Shunt, PaO2 and atelectasis were measured in 11 sheep and 23 pigs with otherwise normal lungs. In pigs, contrasting measurements were available 12 hours after induction of acute respiratory distress syndrome (ARDS). Atelectasis was calculated by computed tomography relative to total lung mass (Mtotal). We logarithmically transformed PaO2 (lnPaO2) to linearize its relationships with shunt and atelectasis. Data are given as median (interquartile range). Results: Mtotal was 768 (715–884) g in sheep and 543 (503–583) g in pigs. Atelectasis was 26 (16–47)% in sheep and 18 (13–23) % in pigs. PaO2 (FiO2 = 1.0) was 242 (106–414) mmHg in sheep and 480 (437–514) mmHg in pigs. Shunt was 39 (29–51)% in sheep and 15 (11–20) % in pigs. Atelectasis correlated closely with lnPaO2 (R2 = 0.78) and shunt (R2 = 0.79) in sheep (P-values<0.0001). The correlation of atelectasis with lnPaO2 (R2 = 0.63) and shunt (R2 = 0.34) was weaker in pigs, but R2 increased to 0.71 for lnPaO2 and 0.72 for shunt 12 hours after induction of ARDS. In both, sheep and pigs, changes in atelectasis correlated strongly with corresponding changes in lnPaO2 and shunt. Discussion and Conclusion: In lung-healthy sheep, atelectasis correlates closely with lnPaO2 and shunt, when blood gases are measured during ventilation with pure oxygen. In lung-healthy pigs, these correlations were significantly weaker, likely because pigs have stronger hypoxic pulmonary vasoconstriction (HPV) than sheep and humans. Nevertheless, correlations improved also in pigs after blunting of HPV during ARDS. In humans, the observed relationships may aid in assessing anaesthesia-related atelectasis.

Background: Atelectasis can provoke pulmonary and non-pulmonary complications after general anaesthesia. Unfortunately, there is no instrument to estimate atelectasis and prompt changes of mechanical ventilation during general anaesthesia. Although arterial partial pressure of oxygen (PaO2) and intrapulmonary shunt have both been suggested to correlate with atelectasis, studies yielded inconsistent results. Therefore, we investigated these correlations. Methods: Shunt, PaO2 and atelectasis were measured in 11 sheep and 23 pigs with otherwise normal lungs. In pigs, contrasting measurements were available 12 hours after induction of acute respiratory distress syndrome (ARDS). Atelectasis was calculated by computed tomography relative to total lung mass (Mtotal). We logarithmically transformed PaO2 (lnPaO2) to linearize its relationships with shunt and atelectasis. Data are given as median (interquartile range). Results: Mtotal was 768 (715–884) g in sheep and 543 (503–583) g in pigs. Atelectasis was 26 (16–47)% in sheep and 18 (13–23) % in pigs. PaO2 (FiO2 = 1.0) was 242 (106–414) mmHg in sheep and 480 (437–514) mmHg in pigs. Shunt was 39 (29–51)% in sheep and 15 (11–20) % in pigs. Atelectasis correlated closely with lnPaO2 (R2 = 0.78) and shunt (R2 = 0.79) in sheep (P-values<0.0001). The correlation of atelectasis with lnPaO2 (R2 = 0.63) and shunt (R2 = 0.34) was weaker in pigs, but R2 increased to 0.71 for lnPaO2 and 0.72 for shunt 12 hours after induction of ARDS. In both, sheep and pigs, changes in atelectasis correlated strongly with corresponding changes in lnPaO2 and shunt. Discussion and Conclusion: In lung-healthy sheep, atelectasis correlates closely with lnPaO2 and shunt, when blood gases are measured during ventilation with pure oxygen. In lung-healthy pigs, these correlations were significantly weaker, likely because pigs have stronger hypoxic pulmonary vasoconstriction (HPV) than sheep and humans. Nevertheless, correlations improved also in pigs after blunting of HPV during ARDS. In humans, the observed relationships may aid in assessing anaesthesia-related atelectasis.

Estudo clínico prospectivo, em 11 pacientes com SARA ou LPA, avaliando o comportamento regional da densidade do tecido pulmonar e do colapso alveolar ao longo dos três eixos do espaço. Foram realizadas tomografias seriadas, após manobra de recrutamento inicial e após níveis de PEEP progressivamente decrescentes. Regressão linear múltipla (R2=0.83) mostrou importante gradiente no eixo gravitacional (p<0.001) e não no sentido céfalo-caudal (p<0.001), nem da direita para a esquerda (p<0.05). Isto corrobora o conceito do pulmão líquido, em que a resultante das pressões exercidas pelo diafragma, estruturas mediastinais e derrames seria transmitida uniformemente pelo tecido pulmonar. Cada um destes níveis isogravitacionais tem uma pressão crítica de fechamento (Pclosing), que é maior do que a pressão superimposta calculada. PEEP tem um efeito homogeneizador sobre o parênquima pulmonar. Dentre os parâmetros clínicos estudados, Pflex mostrou a pior correlação com colapso pulmonar documentado enquanto PO2 e a complacência máxima se mostraram equivalentes. / A prospective clinical study performed on 11 patients with ARDS or ALI with the intention of studying the regional behavior of lung tissue density and alveolar collapse along the three spatial axes. An initial recruitment maneuver was followed by multiple semi-complete CT scans at descending levels of PEEP. Multiple linear regression (R2=0.83) showed a gravitational gradient of densities and collapse (p<0.001) and no cephalo-caudal (p<0.001) or right-toleft increase (p<0.05), corroborating the liquid-like behavior of the lung. Pressure exerted by mediastinal structures, chest wall and effusions is transmitted uniformly throughout the lung. PEEP has a homogenizing effect on lung parenchyma. Among commonly used clinical surrogates, Pflex showed the worst correlation with actual lung collapse, while arterial PO2 and compliance were equivalent.

Estudo clínico prospectivo, em 11 pacientes com SARA ou LPA, avaliando o comportamento regional da densidade do tecido pulmonar e do colapso alveolar ao longo dos três eixos do espaço. Foram realizadas tomografias seriadas, após manobra de recrutamento inicial e após níveis de PEEP progressivamente decrescentes. Regressão linear múltipla (R2=0.83) mostrou importante gradiente no eixo gravitacional (p<0.001) e não no sentido céfalo-caudal (p<0.001), nem da direita para a esquerda (p<0.05). Isto corrobora o conceito do pulmão líquido, em que a resultante das pressões exercidas pelo diafragma, estruturas mediastinais e derrames seria transmitida uniformemente pelo tecido pulmonar. Cada um destes níveis isogravitacionais tem uma pressão crítica de fechamento (Pclosing), que é maior do que a pressão superimposta calculada. PEEP tem um efeito homogeneizador sobre o parênquima pulmonar. Dentre os parâmetros clínicos estudados, Pflex mostrou a pior correlação com colapso pulmonar documentado enquanto PO2 e a complacência máxima se mostraram equivalentes. / A prospective clinical study performed on 11 patients with ARDS or ALI with the intention of studying the regional behavior of lung tissue density and alveolar collapse along the three spatial axes. An initial recruitment maneuver was followed by multiple semi-complete CT scans at descending levels of PEEP. Multiple linear regression (R2=0.83) showed a gravitational gradient of densities and collapse (p<0.001) and no cephalo-caudal (p<0.001) or right-toleft increase (p<0.05), corroborating the liquid-like behavior of the lung. Pressure exerted by mediastinal structures, chest wall and effusions is transmitted uniformly throughout the lung. PEEP has a homogenizing effect on lung parenchyma. Among commonly used clinical surrogates, Pflex showed the worst correlation with actual lung collapse, while arterial PO2 and compliance were equivalent.