Modelo experimental de perfusão pulmonar ex vivo em ratos: avaliação de desempenho de pulmões submetidos à administração de prostaciclina inalada versus parenteral

Abstract

Objective: To present a model of prostaglandin I 2 (PGI 2 ) administration (inhaled vs. parenteral) and to assess the functional performance of the lungs in an ex vivo lung perfusion system. Methods: Forty Wistar rats were anesthetized and placed on mechanical ventilation followed by median sterno-laparotomy and anticoagulation. The main pulmonary artery was cannulated. All animals were maintained on mechanical ventilation and were randomized into four groups (10 rats/group): inhaled saline (IS); parenteral saline (PS); inhaled PGI 2 (IPGI 2 ); and parenteral PGI 2 (PPGI 2 ). The dose of PGI 2 used in the IPGI 2 and PPGI 2 groups was 20 and 10 µg/kg, respectively. The heart-lung blocks were submitted to antegrade perfusion with a low potassium and dextran solution via the pulmonary artery, followed by en bloc extraction and storage at 4°C for 6 h. The heart-lung blocks were then ventilated and perfused in an ex vivo lung perfusion system for 50 min. Respiratory mechanics, hemodynamics, and gas exchange were assessed. Results: Mean pulmonary artery pressure following nebulization decreased in all groups (p < 0.001), with no significant differences among the groups. During the ex vivo perfusion, respiratory mechanics did not differ among the groups, although relative oxygenation capacity decreased significantly in the IS and PS groups (p = 0.04), whereas mean pulmonary artery pressure increased significantly in the IS group. Conclusions: The experimental model of inhaled PGI 2 administration during lung extraction is feasible and reliable. During reperfusion, hemodynamics and gas exchange trended toward better performance with the use of PGI 2 than that with the use of saline.Keywords: Prostaglandins; Lung transplantation; Reperfusion; Models, animal; Rats. ResumoObjetivo: Apresentar um modelo experimental de administração de prostaglandina I 2 (PGI 2 ) por via inalatória vs. parenteral e avaliar o desempenho funcional dos pulmões em um sistema de perfusão pulmonar ex vivo. Métodos: Quarenta ratos Wistar foram anestesiados, ventilados, submetidos a laparotomia com ressecção do esterno e anticoagulados. O tronco da artéria pulmonar foi canulado. Todos os animais foram submetidos a ventilação mecânica. Os animais foram randomizados em quatro grupos (10 ratos/grupo): salina nebulizada (SN); salina parenteral (SP); PGI 2 nebulizada (PGI 2 N); e PGI 2 parenteral (PGI 2 P). A dose de PGI 2 nos grupos PGI 2 N e PGI 2 P foi de 20 e 10 µg/kg, respectivamente. Os blocos cardiopulmonares foram submetidos in situ a perfusão anterógrada com solução de baixo potássio e dextrana a 4°C via artéria pulmonar, extraídos em bloco e armazenados a 4°C por 6 h. Os blocos foram ventilados e perfundidos em um sistema ex vivo por 50 min, sendo obtidas medidas de mecânica ventilatória, hemodinâmica e trocas gasosas. Resultados: Houve redução da pressão arterial pulmonar média após a nebulização em todos os grupos (p < 0,001), sem diferença entre os grupos. Na perfusão ex vivo, a mecânica ventilatória não diferiu entre os grupos. Hou...

Comparison of Celsior and Perfadex lung preservation solutions in rat lungs subjected to 6 and 12 hours of ischemia using an ex-vivo lung perfusion system

“…The ex vivo lung perfusion model is suitable for initial evaluations of lung preservation because of its simplicity, reproducibility, reliability, and low cost compared with larger animal models (13). …”

Publicações do Jornal Brasileiro de Pneumologia

“…There were three studies involving ex vivo experimental models. ( 13 - 15 ) The use of a surgical adhesive for lung repair after lobectomy was tested in rats, ( 16 ) the extracellular matrix of the rat trachea was examined, ( 17 ) an experimental rat model of pulmonary hypertension ( 18 ) was studied, and the use of a self-expanding tracheal stent was tested in rabbits. ( 19 ) Murine models of allergic response ( 20 ) and of protective ventilation strategies ( 21 ) were studied.…”

Modelo experimental de perfusão pulmonar ex vivo em ratos: avaliação histopatológica e de apoptose celular em pulmões preservados com solução de baixo potássio dextrana vs. solução histidina-triptofano-cetoglutarato

“…Further details on extraction and perfusion have been described elsewhere. (10,12) According to the randomization, perfusion was achieved with 20 mL of LPD solution (Perfadex®; Vitrolife, Kungsbacka, Sweden), HTK solution (Custodiol®; Franz Kohler Chemie GMBH, Bensheim, Germany), or NS, at 4°C, administered under a constant pressure of 20 cmH 2 O by raising the flask. At the end of the perfusion, the heart-lung block was extracted and preserved for 6 h or 12 h, according to the predetermined randomization, being prepared and connected to the ex vivo lung perfusion system (IL2 -Isolated Perfused Rat or Guinea Pig Lung System; Harvard Apparatus, Holliston, MA, USA; Hugo Sachs Elektronik, Hugstetten, Germany).…”