Efeitos do Bay 41-2272 na hipertensão pulmonar experimental em cães anestesiados
Cristiane Fonseca Freitas
TESE
Português
(Broch.)
T/UNICAMP F884e
[Effect of Bay 41-2272 in the pulmonary hypertension experimental in anesthetized dogs]
Campinas, SP : [s.n.], 2007.
149f. : il.
Orientador: Edson Antunes
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
Resumo: Neste estudo, investigamos os efeitos protetores do BAY 41-2272 sobre a hipertensao pulmonar induzida pelo complexo heparina-protamina e hipoxia em cães anestesiados. Os animais foram anestesiados com pentobarbital sodico (Hypnol, 30mg/kg, iv) combinado com citrato de fentanila (0,01...
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Resumo: Neste estudo, investigamos os efeitos protetores do BAY 41-2272 sobre a hipertensao pulmonar induzida pelo complexo heparina-protamina e hipoxia em cães anestesiados. Os animais foram anestesiados com pentobarbital sodico (Hypnol, 30mg/kg, iv) combinado com citrato de fentanila (0,01 mg/kg/h, i.v.) e diazepam (0,25mg/kg/h, iv). A hipertensao pulmonar pelo complexo heparina-protamina foi induzida com a administracao de 500 UI/kg de heparina, seguida da administracao de protamina (10 mg/kg). A interacao heparina-protamina causou aumento de aproximadamente 350% da pressao media da arteria pulmonar (PMAP), acompanhado de aumento significativo do indice de resistencia vascular pulmonar (IRVP) e da pressao capilar pulmonar (PcP). Este aumento foi significativo 2 min apos a injecao de protamina, mantendo-se significativamente elevado ate aproximadamente 5 minutos apos administracao da mesma. Ao mesmo tempo em que se detectou a hipertensao pulmonar, observamos reducao significativa da pressao arterial media (PAM). Observamos ainda um aumento significativo da frequencia cardiaca (FC) aos 2 minutos apos administracao da protamina com discreta diminuicao do indice cardiaco (IC). O indice de resistencia vascular sistemica (IRVS) nao sofreu alteracoes significativas. A saturacao do oxigenio (SpO2) foi significativamente diminuida apos a formacao do complexo heparina-protamina. Nos animais tratados com BAY 41-2272 (10 /kg/min, i.v.), observamos reducao marcante do aumento da PMAP, do IRVP e da PcP. Por outro lado, este tratamento potencializou a reducao da PAM. Alem disso, o BAY 41-2272 reduziu significantemente o IRVS e aumentou a FC. A diminuicao da SpO2 foi atenuada significativamente pelo BAY 41- 2272. Os niveis plasmaticos de GMPc foram dosados aos 2 min apos a formacao do complexo heparina-protamina, tendo-se mostrado elevados no grupo tratado com o BAY41-2272. O tempo de tromboplastina parcial ativado (TTPA) nao apresentou alteração significativa no tratamento com o BAY 41-2272. O veiculo do BAY 41-2272 (DMSO 30%) nao alterou significativamente os parametros estudados. A hipertensao pulmonar por hipoxia foi induzida com a instalacao de uma baixa tensao de oxigenio (FiO2=12%). Nesta circunstancia, a PMAP elevou-se em aproximadamente 280% aos 5 minutos, mantendo-se significativamente elevada ate 15 minutos apos instalacao da hipoxia. A elevacao da PMAP foi acompanhada de aumentos significativos no IRVP e PcP. A PAM, IRVS, FC e IC nao apresentaram alterações significativas. A SpO2 diminuiu na presenca da hipoxia. O tratamento com BAY 41-2272 (10 /kg/min, i.v.), reduziu significativamente a PMAP, PcP e IRVP. O IRVS foi significativamente potencializado pelo BAY 41-2272. A PAM, FC e IC nao alteraram significativamente. A diminuicao da SpO2 foi atenuada significativamente pelo BAY 41- 2272. Os niveis plasmaticos de GMPc elevaram-se significativamente no grupo tratado com o BAY 41-2272. Em conclusao, o BAY 41-2272 atenuou a acao vasoconstritora pulmonar induzida pelo complexo heparina-protamina e hipoxia levando a uma prevencao da hipertensao pulmonar.
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Abstract: In this study, we investigated the protective effect of BAY 41-2272 on the pulmonary hypertension induced by the protamine-heparin complex and hypoxia in anaesthetized dogs. The animals were anaesthetized with pentobarbital sodium (Hypnol, 30 mg/kg, i.v.) combined with fentanil citrate...
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Abstract: In this study, we investigated the protective effect of BAY 41-2272 on the pulmonary hypertension induced by the protamine-heparin complex and hypoxia in anaesthetized dogs. The animals were anaesthetized with pentobarbital sodium (Hypnol, 30 mg/kg, i.v.) combined with fentanil citrate (0.01 mg/kg/h, i.v.) and diazepam (0.25mg/kg/h, i.v.). The pulmonary hypertension for the protamine-heparin complex was induced by the administration of 500 UI/kg of heparin, followed by protamine (10mg/Kg), causing an increase of approximately 350% of the mean pulmonary arterial pressure (MPAP), followed by a significant increase of the index of pulmonary vascular resistance (IPVR) and index of pulmonary capillary wedge pressure (PcWP). This increase was significant from 2 min to 5 min after the protamine administration. Concomitantly to the pulmonary hypertension, we observed a significant decrease of the mean arterial blood pressure (MABP). We also observed a significant increase of the heart rate (HR) 2 min after administration of protamine with a discreet reduction of the cardiac index (IC). The index of systemic vascular resistance (ISVR) was not changed. The saturation of the oxygen (SpO2) was significantly decreased after the formation of heparin-protamine complex. In the animals treated with BAY 41-2272 (10 /kg/min, i.v.), we observed a marked reduction of MPAP, IPVR and PcWP. On the other hand, BAY 41-2272 potentiated the reduction of MABP after protamine administration. Furthermore, BAY 41-2272 significantly reduced the ISVR and increased HR. Additionally, the reduction of SpO2 was attenuated significantly by BAY 41-2272. The plasma levels of cGMP, measured at 2 min after the formation of the protamine-heparin complex, were higher in BAY 41-2272-treated animals. The activated partial thromboplastin time (APTT) was not altered in the BAY 41-2272-treated group. The vehicle of BAY 41-2272 (DMSO 30%) did not alter any of the parameters evaluated. The hypoxia-induced pulmonary hypertension was obtained with the installation of low tension of oxygen (FiO2=12%). In this condition, MPAP was significantly elevated (280%) from 5 min to 15 min after hypoxia installation. This elevation was accompanied by significant increases in both IPVR and PcWP. The MABP, ISVR, HR and IC were not significantly altered. The SpO2 was decreased by hypoxia. The treatment with BAY 41-2272 (10 /kg/min, i.v.) reduced significantly the MPAP, PcWP and IPVR. The ISVR reduction was significantly potentiated by BAY 41-2272. The MABP, HR and IC were not modified by BAY 41-2272, while the reduction of the SpO2 was significantly attenuated. The plasma levels of cGMP were significantly increased in the BAY 41-2272-treated group. In conclusion, treatment with BAY 41-2272 attenuates the pulmonary vasoconstrictor action induced by heparin-protamine complex or hypoxia, leading to the prevention of pulmonary hypertension.
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Antunes, Edson, 1960-
Orientador
Zanesco, Angelina
Avaliador
Teixeira, Cleber Evandro, 1973-2007
Avaliador
Nadruz Junior, Wilson, 1973-
Avaliador
Efeitos do Bay 41-2272 na hipertensão pulmonar experimental em cães anestesiados
Cristiane Fonseca Freitas
Efeitos do Bay 41-2272 na hipertensão pulmonar experimental em cães anestesiados
Cristiane Fonseca Freitas
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