Ozone Therapy Protects Against Rejection in a Lung Transplantation Model: A New Treatment?

BACKGROUND: No satisfactory treatment exists for chronic rejection (CR) after lung transplantation (LT). Our objective was to assess whether ozone (O3) treatment could ameliorate CR. METHODS: Male Sprague-Dawley inbred rats (n = 36) were randomly assigned into four groups: (1) control (n = 6), (2) sham (n = 6), (3) LT (n = 12), and (4) O3-LT (n = 12). Animals underwent left LT. O3 was rectally administered daily for 2 weeks before LT (from 20 to 50 µg) and 3 times/wk (50 µg/dose) up to 3 months. CR; acute rejection; and Hspb27, Prdx, Epas1, Gpx3, Vegfa, Sftpa1, Sftpb, Plvap, Klf2, Cldn5, Thbd, Dsip, Fmo2, and Sepp1 mRNA gene expression were determined. RESULTS: Severe CR was observed in all animals of LT group, but none of the O3-LT animals showed signs of CR, just a mild acute rejection was observed in 1 animal. A significant decrease of Hspb27, Prdx, Epas1, Gpx3, Vegfa, Sftpa1, Sftpb, Plvap, Klf2, Cldn5, Thbd, Dsip, and Fmo2 gene expression in the O3-LT group was observed CONCLUSIONS: O3 therapy significantly delayed the onset of CR regulating the expression of genes involved in its pathogenesis. No known immunosuppressive therapy has been capable of achieving similar results. From a translational point of view, O3 therapy could become a new adjuvant treatment for CR in patients undergoing LT.

Autologous platelet-poor plasma decreases the bronchial stump necrosis in rat.

BACKGROUND: Necrosis of the bronchial stump is a very important trigger for bronchopleural fistula. The administration of local autologous platelet-poor plasma (PPP) could protect the bronchial stump. MATERIALS AND METHODS: Left pneumonectomy was performed in 25 Sprague-Dawley rats. Animals were randomly assigned to a control group (n=13) and PPP group (n=12). PPP was locally administered on the bronchial stump after pneumonectomy. We analyzed histologic changes in the bronchial stump and messenger RNA expression changes of genes involved in wound repair at 10 and 20 d. RESULTS: Local PPP treatment produced a mass of fibrous tissue surrounding the bronchial stump and significantly decreased the presence of necrosis at 20 d. PPP increased the expression of insulin like growth factor 1 at 10 d although it did not reach statistical significance. CONCLUSIONS: Our findings indicate that local PPP treatment of the bronchial stump after pneumonectomy decreased necrosis and could have a protective effect on the bronchial stump.

Modificaciones técnicas del modelo de trasplante pulmonar ortotópico en ratas con donantes en muerte cerebral / Technical Modifications of the Orthotopic Lung Transplantation Model in Rats with Brain-Dead Donors

Introducción: El trasplante microquirúrgico de pulmón en ratas ha permitido adquirir nuevos conocimientos sobre el trasplante de pulmón. Sin embargo, algunos aspectos de la técnica de trasplante en humanos aún no han sido incluidos en este modelo, lo que podría interferir en la interpretación clínica y en la extrapolación de los resultados. Método: Se han realizado 20 trasplantes pulmonares izquierdos con la técnica de manguitos (cuff) incorporando algunas modificaciones técnicas como la inducción de la muerte cerebral, el control del tiempo de isquemia, la perfusión retrógrada en el donante y la reperfusión secuencial controlada del pulmón implantado en el receptor. Resultados: La supervivencia ha sido del 80%. Los pulmones trasplantados mostraron una adecuada perfusión y ventilación con buena permeabilidad de las anastomosis. Se han observado signos de isquemia-reperfusión en todos los animales, y de rechazo agudo leve en la mitad de ellos. Conclusiones: El modelo que presentamos es válido y similar al procedimiento que se realiza en humanos, lo que reduciría el número de posibles variables derivadas de la técnica quirúrgica a la hora de extrapolar los resultados a la clínica(AU)

Background: Microsurgical lung transplantation in rats has allowed us to obtain new knowledge about lung transplantation. However, some aspects in human transplantation technique still have not been included in this model, which could interfere with the clinical interpretation and extrapolation of results .Methods: Twenty left lung transplantations were performed with a cuff technique and technical modifications, such as brain death induction, the control of ischemia time and retrograde perfusion in the donor and the controlled sequential reperfusion of the implanted lung in the recipient. Results: Survival rate was 80%. The transplanted lungs showed proper perfusion and ventilation with good permeability of the anastomoses. Signs of ischemia-reperfusion injury were observed in all animals while mild acute rejection was seen in half of them. Conclusions: The model shown proves valid and is very similar to the procedure carried out in humans, which would reduce the number of possible variables derived from the surgical technique when extrapolating the study results to clinical use(AU)

Technical modifications of the orthotopic lung transplantation model in rats with brain-dead donors.

BACKGROUND: Microsurgical lung transplantation in rats has allowed us to obtain new knowledge about lung transplantation. However, some aspects in human transplantation technique still have not been included in this model, which could interfere with the clinical interpretation and extrapolation of results. METHODS: Twenty left lung transplantations were performed with a cuff technique and technical modifications, such as brain death induction, the control of ischemia time and retrograde perfusion in the donor and the controlled sequential reperfusion of the implanted lung in the recipient. RESULTS: Survival rate was 80%. The transplanted lungs showed proper perfusion and ventilation with good permeability of the anastomoses. Signs of ischemia-reperfusion injury were observed in all animals while mild acute rejection was seen in half of them. CONCLUSIONS: The model shown proves valid and is very similar to the procedure carried out in humans, which would reduce the number of possible variables derived from the surgical technique when extrapolating the study results to clinical use.