Modelo experimental de perfusão pulmonar ex vivo em ratos: avaliação de desempenho de pulmões submetidos à administração de prostaciclina inalada versus parenteral / An experimental rat model of ex vivo lung perfusion for the assessment of lungs after prostacyclin administration: inhaled versus parenteral routes

OBJETIVO: Apresentar um modelo experimental de administração de prostaglandina I2 (PGI2) 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); PGI2 nebulizada (PGI2N); e PGI2 parenteral (PGI2P). A dose de PGI2 nos grupos PGI2N e PGI2P 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 4ºC via artéria pulmonar, extraídos em bloco e armazenados a 4ºC 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. Houve redução da capacidade relativa de oxigenação ao longo da perfusão nos grupos SN e SP (p = 0,04), e houve aumento significativo da pressão arterial pulmonar no grupo SN. CONCLUSÕES: O modelo experimental de administração de PGI2 na extração pulmonar é exequível e confiável. Na reperfusão, os resultados de hemodinâmica e de trocas gasosas demonstraram tendência a um melhor desempenho com o uso de PGI2 do que com solução salina.

OBJECTIVE:To present a model of prostaglandin I2 (PGI2) 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 PGI2 (IPGI2); and parenteral PGI2 (PPGI2). The dose of PGI2 used in the IPGI2 and PPGI2 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 4ºC 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 PGI2 administration during lung extraction is feasible and reliable. During reperfusion, hemodynamics and gas exchange trended toward better performance with the use of PGI2 than that with the use of saline.

Iloprosta reduz o dano colônico na colite isquêmica em ratos / Iloprost reduces colonic injury in ischemic colitis in rats

PURPOSE: Evaluate the effects of iloprost administration in the early period of ischemic colitis and the mechanism that how these effects develop. METHODS: Thirty two Wistar albino female rats with an average weight of 220g were divided into four groups of eight rats. In group 1 the rats were given iloprost and sacrificed after 24 hours and in group 2 they were sacrificed after 24 hours without any iloprost. The rats in group 3 were administrated iloprost and sacrificed after 72 hours and in group 4 they were sacrificed at 72th hour without iloprost. The differences between the groups as tissue damage, vascularization or apoptosis were assessed statistically. RESULTS: Oxidative damage and apoptosis were less pronounced and vascularization was better developed in rats that were given iloprost and sacrificed at 24th hour later in contrast to the rats that were not treated with iloprost. But there was no statistical difference among the groups at 72th hour. CONCLUSION: Iloprost inhibited leucocyte infiltration, decreased proinflammatory cytokines and enhanced angiogenesis so that the oxidative stress and inflammatory response decreased resulting in lesser tissue damage.

OBJETIVO: Avaliar os efeitos da administração de iloprosta no período precoce da colite isquêmica e o mecanismo da evolução destes efeitos. MÉTODOS: Trinta e dois ratos Wistar fêmeas em torno de 220g foram distribuídos em quatro grupos de oito ratos. No grupo 1 administração de iloprosta e sacrificados após 24 horas; no grupo 2 foram sacrificados após 24 horas sem iloprosta; no grupo 3 foi administrado iloprosta e sacrificados após 72 horas; no grupo 4 foram sacrificados após 72 horas sem Iloprosta. As diferenças entre os grupos no referente a dano tecidual. vascularização ou apoptose foi apurada estatisticamente. RESULTADOS: Dano oxidativo e apoptose foram menos acentuados e a vascularização foi melhor nos ratos que receberam iloprosta e sacrificados após 24 horas em contraste com os ratos que não receberam iloprosta. Porém, não houve diferença estatisticamente significante entre os grupos de 72 horas. CONCLUSÃO: Iloprosta inibe infiltração leucocitária, diminui a ação inflamatória de citoquinas e estimula angiogênese resultando em menor dano tecidual.

Combination therapy of prostacyclin for pulmonary hypertension in congenital heart disease.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a recognized complication of congenital heart disease. Despite differences in etiology and pathophysiology, successful therapy for idiopathic PAH may benefit in patients with congenital heart disease. We theorized that combination of oral and aerosolization prostacyclin will benefit this group of patients in long-term. MATERIAL AND METHOD: The study design was single group and open label study with intention to treat for patients with congenital heart disease with pulmonary artery (PA pressure) more than 50% of systemic pressure. All patients were given a combination of orally given beraprost sodium and inhalation of iloprost for 12 months. Data were collected prospectively consisting of functional class, O2 saturation, 6-minute walk test and right ventricular systolic pressure (RVSP). RESULTS: There were 23 patients with an average right ventricular systolic pressure (+/- SD) of 94.8 +/- 14.5 mmHg and with average age of 27.8 +/- 14.9 years (2.5 to 50 years). The average oxygen saturation was 87.9 +/- 7 %. There were 12 patients with post surgical repair or cardiac catheterization interventional procedure and 11 with and Eisenmenger's syndrome. There were significant improvement of 6-minute-walk test from an average of 268 +/- 70 meters to 308 +/- 57 meters at the end of 12 months. The functional class of patients was also improving. However, there were no significant different in oxygen saturation. CONCLUSION: Combination therapy of oral and inhalation of aerosolized vasodilators is a fascinating concept in the therapy of pulmonary hypertension. Treated patients showed an improvement in exercise capacity and right ventricular systolic pressure without a worsening in oxygen saturation.