Comparação de dois modelos experimentais de hipertensão pulmonar

Abstract

Objective: To compare two models of pulmonary hypertension (monocrotaline and monocrotaline+pneumonectomy) regarding hemodynamic severity, structure of pulmonary arteries, inflammatory markers (IL-1 and PDGF), and 45-day survival. Methods: We used 80 Sprague-Dawley rats in two study protocols: structural analysis; and survival analysis. The rats were divided into four groups: control; monocrotaline (M), pneumonectomy (P), and monocrotaline+pneumonectomy (M+P). In the structural analysis protocol, 40 rats (10/group) were catheterized for the determination of hemodynamic variables, followed by euthanasia for the removal of heart and lung tissue. The right ventricle (RV) was dissected from the interventricular septum (IS), and the ratio between RV weight and the weight of the left ventricle (LV) plus IS (RV/LV+IS) was taken as the index of RV hypertrophy. In lung tissues, we performed histological analyses, as well as using ELISA to determine IL-1 and PDGF levels. In the survival protocol, 40 animals (10/group) were followed for 45 days. Results: The M and M+P rats developed pulmonary hypertension, whereas the control and P rats did not. The RV/LV+IS ratio was significantly higher in M+P rats than in M rats, as well as being significantly higher in M and M+P rats than in control and P rats. There were no significant differences between the M and M+P rats regarding the area of the medial layer of the pulmonary arteries; IL-1 and PDGF levels; or survival. Conclusions: On the basis of our results, we cannot conclude that the monocrotaline+pneumonectomy model is superior to the monocrotaline model. Keywords:Monocrotaline; Hypertension, pulmonary; Pneumonectomy; Interleukin-1; Receptor, plateletderived growth factor beta. ResumoObjetivo: Comparar dois modelos de hipertensão pulmonar (monocrotalina e monocrotalina+pneumonectomia) em relação à gravidade hemodinâmica, estrutura de artérias pulmonares, marcadores inflamatórios (IL-1 e PDGF) e sobrevida em 45 dias. Métodos: Foram utilizados 80 ratos Sprague-Dawley em dois protocolos de estudo: análise estrutural e de sobrevida. Os animais foram divididos em quatro grupos: controle, monocrotalina (M), pneumonectomia (P) e monocrotalina+pneumonectomia (M+P). Para a análise estrutural, 40 animais (10/grupo) foram cateterizados após 28 dias para a medição dos valores hemodinâmicos e sacrificados, obtendo-se tecidos cardíaco e pulmonar. O ventrículo direito (VD) foi dissecado do septo interventricular (SI), e a relação do peso do VD e do peso do ventrículo esquerdo (VE) com o SI foi obtida como índice de hipertrofia de VD. No tecido pulmonar, foram realizadas análises histológicas e dosados IL-1 e PDGF por ELISA. Para o estudo de sobrevida, 40 animais (10/grupo) foram observados por 45 dias. Resultados: Os grupos M e M+P apresentaram hipertensão pulmonar em relação aos demais. Houve um aumento significativo da relação VD/VE+S no grupo M+P em relação aos demais. Não houve diferenças significativas entre os grupos M e M+P quanto à área da camada média das artérias pulmonare...

Lodenafil treatment in the monocrotaline model of pulmonary hypertension in rats

“…Survival in monocrotaline-treated rats is significantly lower, as reported in a previous study, ( 8 ) and this happens in parallel with progressive vascular involvement and progressive involvement of the RV. The same can be observed in humans with PAH, who have decreased survival because of the development of pulmonary vascular remodeling associated with progressive failure of the RV, with this being the leading cause of death in patients with PAH.…”

“…The hemodynamic measurements were performed by inserting an umbilical catheter into the external jugular vein, the catheter being connected to a pressure transducer (HP 1295C; Hewlett-Packard, Palo Alto, CA, USA) coupled to a hemodynamic monitor (Monitox Dx 2020; Hewlett Packard), in accordance with a technique described in a previous study. ( 8 ) Mean pulmonary artery pressure (mPAP) was thus measured.…”

“…The ratio of RV weight to LV+S weight (i.e., RV/LV+S) was taken as the index of RV hypertrophy. ( 8 )…”

Compensatory lung growth after bilobectomy in emphysematous rats

“…Fernandez et al [ 9 ] found that pulmonary hypertension was proportional to the amount of lung mass excised. In addition, Polonio et al [ 49 ] showed that rats which underwent pneumonectomy and treatment with monocrotaline developed hypertension. We used an indirect technique to quantify the index of right ventricular mass relative to body mass and observed an increase in this index only in the Saline+LBX group.…”

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.…”