Pathophysiological and Clinical Significance of Crotalus durissus cascavella Venom-Induced Pulmonary Impairment in a Murine Model.

Crotalus venom has broad biological activity, including neurotoxic, myotoxic, hematologic, and cytotoxic compounds that induce severe systemic repercussions. We evaluated the pathophysiological and clinical significance of Crotalus durissus cascavella (Cdc) venom-induced pulmonary impairment in mice. We conducted a randomized experimental study, involving 72 animals intraperitoneally inoculated with saline solution in the control group (CG), as well as venom in the experimental group (EG). The animals were euthanized at predetermined intervals (1 h, 3 h, 6 h, 12 h, 24 h, and 48 h), and lung fragments were collected for H&E and Masson histological analysis. The CG did not present inflammatory alterations in pulmonary parenchyma. In the EG, interstitial and alveolar swelling, necrosis, septal losses followed by alveolar distensions, and areas of atelectasis in the pulmonary parenchyma were observed after three hours. The EG morphometric analysis presented pulmonary inflammatory infiltrates at all time intervals, being more significant at three and six (p = 0.035) and six and 12 h (p = 0.006). The necrosis zones were significant at intervals of one and 24 h (p = 0.001), one and 48 h (p = 0.001), and three and 48 h (p = 0.035). Crotalus durissus cascavella venom induces a diffuse, heterogeneous, and acute inflammatory injury in the pulmonary parenchyma, with potential clinical implications for respiratory mechanics and gas exchange. The early recognition and prompt treatment of this condition are essential to prevent further lung injury and to improve outcomes.

Evaluation of systemic inflammatory response and lung injury induced by Crotalus durissus cascavella venom.

This study investigated the systemic inflammatory response and mechanism of pulmonary lesions induced by Crotalus durissus cascavella venom in murine in the state of Bahia. In order to investigate T helper Th1, Th2 and Th17 lymphocyte profiles, we measured interleukin (IL) -2, IL-4, IL-6, IL-10, IL-17, tumor necrosis factor (TNF) and interferon gamma (IFN-γ) levels in the peritoneal fluid and macerated lungs of mice and histopathological alterations at the specific time windows of 1h, 3h, 6h, 12h, 24h and 48h after inoculation with Crotalus durissus cascavella venom. The data demonstrated an increase of acute-phase cytokines (IL-6 and TNF) in the first hours after inoculation, with a subsequent increase in IL-10 and IL-4, suggesting immune response modulation for the Th2 profile. The histopathological analysis showed significant morphological alterations, compatible with acute pulmonary lesions, with polymorphonuclear leukocyte (PMN) infiltration, intra-alveolar edema, congestion, hemorrhage and atelectasis. These findings advance our understanding of the dynamics of envenomation and contribute to improve clinical management and antiophidic therapy for individuals exposed to venom.

Quanto tempo de oclusão é necessário para avaliar a pressão inspiratória máxima pelo método da válvula expiratória unidirecional em sujeitos sem via aérea artificial? / ¿Cuánto tiempo de oclusión es necesario para evaluar la presión inspiratoria máxima por el método de la válvula espiratoria unidireccional en sujetos sin vía aérea artificial? / How much occlusion time is necessary to assess maximal inspiratory pressure by the unidirectional expiratory valve method in subjects without artificial airway?

RESUMO O objetivo desse estudo foi determinar o tempo de oclusão necessário para avaliar a pressão inspiratória máxima (PIMáx) obtida pelo método da válvula expiratória unidirecional em sujeitos sem via aérea artificial. Foram avaliados 31 sujeitos, com idade entre 18 e 60 anos. A PIMáx foi avaliada pelo método convencional (PIMáxconv) e pelo método da válvula expiratória unidirecional (PIMáxuni), sendo a ordem de avaliação definida por meio de sorteio. Para a medida da PIMáxuni, um manovacuômetro digital foi acoplado a uma válvula expiratória unidirecional e máscara orofacial por 20 segundos de oclusão. Nesse período, todos os sujeitos foram encorajados a realizar esforços inspiratórios máximos. Para definir a ótima duração da manobra, o tempo de esforço foi dividido a cada intervalo de 5 segundos (0-5s, 0-10s, 0-15s, 0-20s). Os intervalos de tempo para obtenção da PIMáxuni foram comparados por meio do teste de ANOVA One-way. Para comparação das médias dos valores de PIMáxconv e PIMáxuni, foi utilizado o teste t de Student. O nível de significância foi de 5%. A média dos valores da PIMáxconv foi de -102,5±23,9 cmH2O, enquanto que a PIMáxuni foi de -117,3±24,8 cmH2O (p<0,001). O valor absoluto máximo da PIMáxuni foi alcançado dentro do intervalo de 0-20 segundos, que foi significativamente superior ao valor absoluto máximo obtido nos primeiros 5 segundos (p=0,036). O tempo de oclusão necessário para avaliar a PIMáx pelo método da válvula expiratória unidirecional em sujeitos colaborativos sem via aérea artificial deve ser de pelo menos 20 segundos.

RESUMEN Este estudio busca determinar cuánto tiempo de oclusión es necesario para obtener la presión inspiratoria máxima (PIMáx) por medio del método de la válvula espiratoria unidireccional en individuos sin vía aérea artificial. Se evaluaron 31 sujetos de entre 18 y 60 años de edad. La PIMáx se evaluó mediante el método estándar (PIMáxest) y el método de válvula espiratoria unidireccional (PIMáxuni), siendo que el orden de evaluación se estableció por medio de un sorteo. Para el PIMáxuni, un manovacuómetro digital se ha conectado a una válvula espiratoria unidireccional y una máscara orofacial durante 20 segundos de oclusión. Durante este período, se alentó a los individuos a hacer esfuerzos respiratorios máximos. Para definir la óptima duración de la maniobra, el tiempo de esfuerzo se dividió en intervalos de cinco segundos (0-5s, 0-10s, 0-15s, 0-20s). Los intervalos del tiempo para el PIMáxuni se compararon mediante la prueba ANOVA one-way. Las medias de los valores de PIMáxest y de PIMáxuni se compararon mediante la prueba pareada t de Student. El nivel de significancia se estableció en el 5%. La media de los valores de PIMáxest (-102,5±23,9 cmH2O) presentó una diferencia estadísticamente significativa en comparación con la media de los valores de PIMáxuni (-117,3±24,8 cmH2O, p<0,001). El valor absoluto máximo obtenido de PIMáxuni estaba dentro del intervalo de 0-20 segundos, que fue significativamente superior del valor absoluto máximo durante los primeros 5 segundos (p=0,036). El tiempo de oclusión necesario para registrar la PIMáx por el método de válvula espiratoria unidireccional en individuos colaborativos sin vía aérea artificial debe ser de al menos 20 segundos.

ABSTRACT The aim of this study was to determine how much occlusion time is necessary to obtain maximal inspiratory pressure (MIP) by the unidirectional expiratory valve method in subjects without artificial airway. Thirty-one subjects aged 18-60 years were evaluated. MIP was evaluated by the standard method (MIPstan) and by the unidirectional expiratory valve method MIPuni, with the order of evaluation determined randomly by lot. For MIPuni measurement, a digital vacuum manometer was attached to a unidirectional expiratory valve and an orofacial mask for 20 seconds of occlusion. During this period, all subjects were encouraged to make maximal respiratory efforts. To define the optimum duration of the maneuver, the 20 seconds of effort were partitioned at every five-second interval (0-5s, 0-10s, 0-15s, 0-20s). The time intervals for obtaining MIPuni were compared with the one-way ANOVA test. The mean values of the standard method and the unidirectional expiratory valve method were compared using the paired Student's t-test. The significance level was established at 5%. The mean values for the MIPstan (-102.5±23.9 cmH2O) presented a statistically significant difference as compared to the mean values for MIPuni (-117.3±24.8 cmH2O; p<0.001). Maximal peak values for MIPuni were achieved within the 20-second time window, which differed significantly from the peak values obtained during the first five seconds (p=0.036). The occlusion time necessary to record MIP by the unidirectional expiratory valve method in collaborative subjects without artificial airway should be of at least 20 seconds.

Unidirectional Expiratory Valve Method to Assess Maximal Inspiratory Pressure in Individuals without Artificial Airway.

INTRODUCTION: Maximal Inspiratory Pressure (MIP) is considered an effective method to estimate strength of inspiratory muscles, but still leads to false positive diagnosis. Although MIP assessment with unidirectional expiratory valve method has been used in patients undergoing mechanical ventilation, no previous studies investigated the application of this method in subjects without artificial airway. OBJECTIVES: This study aimed to compare the MIP values assessed by standard method (MIPsta) and by unidirectional expiratory valve method (MIPuni) in subjects with spontaneous breathing without artificial airway. MIPuni reproducibility was also evaluated. METHODS: This was a crossover design study, and 31 subjects performed MIPsta and MIPuni in a random order. MIPsta measured MIP maintaining negative pressure for at least one second after forceful expiration. MIPuni evaluated MIP using a unidirectional expiratory valve attached to a face mask and was conducted by two evaluators (A and B) at two moments (Tests 1 and 2) to determine interobserver and intraobserver reproducibility of MIP values. Intraclass correlation coefficient (ICC[2,1]) was used to determine intraobserver and interobserver reproducibility. RESULTS: The mean values for MIPuni were 14.3% higher (-117.3 ± 24.8 cmH2O) than the mean values for MIPsta (-102.5 ± 23.9 cmH2O) (p<0.001). Interobserver reproducibility assessment showed very high correlation for Test 1 (ICC[2,1] = 0.91), and high correlation for Test 2 (ICC[2,1] = 0.88). The assessment of the intraobserver reproducibility showed high correlation for evaluator A (ICC[2,1] = 0.86) and evaluator B (ICC[2,1] = 0.77). CONCLUSIONS: MIPuni presented higher values when compared with MIPsta and proved to be reproducible in subjects with spontaneous breathing without artificial airway.