ANALISIS COMPARATIVO DE ANTICUERPOS MONOCLONALES EN LA RESPUESTA INFLAMATORIA PULMONAR EN UN MODELO EXPERIMENTAL DE RATAS SOMETIDAS A VENTILACIÓN MECÁNICA

Enrique Correger, Josefina Marcos, Damián Sotelo, Graciela Laguens, Pablo Stringa

Resumen


Summary

Objective: To compare the role of cytokine inhibition in two groups previously treated with mechanical ventilation (MV) with anti TNF and anti IL6 in lung damage caused by MV in an experimental in vivo model of VILI.

Materials and Methods: 24 Wistar rats were mechanically ventilated for 2 hours with a FiO2 = 0.40 and randomized into 4 groups:

• Low VT group (n = 6): VT 7ml/kg, PEEP 5 cmH2O;

• High VT group (n = 6): VT 35 ml/kg, ZEEP;

• Anti IL-6 group (n = 6): VT 25 ml/kg, ZEEP and 30 mg/kg intraperitoneal Tocilizumab 24hs prior to MV;

• Anti TNFα group (n = 6): VT 25 ml/kg, ZEEP and 100 µg/kg of intraperitoneal Adalimumab 24hs prior to MV.

Histological damage measured by Villar et al., pulmonary edema (pulmonary water), pulmonary compliance, and hemodynamics measured with TAM in the different study groups were evaluated. The data were analyzed with t Test, p significant <0.05.

Results: No statistically significant differences were found in lung mechanics as in TAM in both groups after injurious ventilation for 2 hours. In the Anti TNF group, a significantly lower histological damage score was observed, compared with the anti-IL6 group. Greater weight gain was also observed in the anti IL6 group (p 0.0001).

Conclusion: Under these experimental conditions of mechanical pulmonary stress, after 2 hours of damaging VM, a monoclonal anti TNF improved the histological score and the reduction of pulmonary edema formation in further effective way than the inhibition of IL6, even this effect was observed in the absence of evaluable manifestations in lung mechanics and cardiac function.

 

 

Resumen

Objetivo: Comparar el rol de la inhibición de citoquinas, en dos grupos tratados previamente a la ventilación mecánica (VM) con anti TNF y anti IL6, en el daño pulmonar ocasionado por la VM en un modelo experimental in vivo de VILI.

Materiales y Métodos: 24 ratas Wistar fueron ventiladas mecánicamente, durante 2 horas, con una FiO2= 0,40 y aleatorizadas en 4 grupos:

  • Grupo bajo VT (n=6): VT 7ml/kg, PEEP5 cmH2O;
  • Grupo alto VT (n=6): VT 35 ml/kg, ZEEP;
  • Grupo anti IL-6 (n=6): VT 25 ml/kg, ZEEP y 30mg/kg de Tocilizumab intraperitoneal 24hs previas a la VM;
  • Grupo anti TNFα (n=6): VT 25 ml/kg, ZEEP y 100ug/kg de Adalimumab intraperitoneal 24hs previas a la VM.

Se evaluó el daño histológico medido según score de Villar et al, edema pulmonar (agua pulmonar), distensibilidad pulmonar, y hemodinamia medida con PAM en los diferentes grupos de estudio. Los datos fueron analizados con test de t, p significativa <0,05.

Resultados: No se encontraron diferencias estadísticamente significativas en la mecánica pulmonar como tampoco en la TAM en ambos grupos luego de la ventilación injuriante durante 2 horas. En el grupo tratado con anti TNF se observó un menor daño histológico (score), en forma significativa, comparados con el grupo anti IL6.  Asimismo se evidenció mayor ganancia de peso en el grupo anti IL6 (p 0.0001).

Conclusión: Bajo estas condiciones experimentales de estrés pulmonar mecánico, luego de 2 horas de VM lesiva, un Ac monoclonal anti TNF mejoró el score histológico así como la reducción de la formación de edema pulmonar de una manera más efectiva que la inhibición del IL6, incluso este efecto se observó en ausencia de manifestaciones evaluables en la mecánica pulmonar y la función cardíaca.


Palabras clave


VILI, SDRA, Laboratorio de injuria pulmonar

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Referencias


Referencias

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