RESUMEN
Abstract Purpose: To analyze the effect of methylene blue (MB) therapy during the liver ischemia-reperfusion injury (I/R) process. Methods: Thirty-five male Wistar rats were used, (70%) submitted to partial ischemia (IR) or not (NIR) (30%) were obtained from the same animal. These animals were divided into six groups: 1) Sham (SH), 2) Sham with MB (SH-MB); 3) I/R, submitted to 60 minutes of partial ischemia and 15 minutes of reperfusion; 4) NI/R, without I/R obtained from the same animal of group I/R; 5) I/R-MB submitted to I/R and MB and 6) NI/R-MB, without I/R. Mitochondrial function was evaluated. Osmotic swelling of mitochondria as well as the determination of malondialdehyde (MDA) was evaluated. Serum (ALT/AST) dosages were also performed. MB was used at the concentration of 15mg/kg, 15 minutes before hepatic reperfusion. Statistical analysis was done by the Mann Whitney test at 5%. Results: State 3 shows inhibition in all ischemic groups. State 4 was increased in all groups, except the I/R-MB and NI/R-MB groups. RCR showed a decrease in all I/R and NI/R groups. Mitochondrial osmotic swelling showed an increase in all I/R NI/R groups in the presence or absence of MB. About MDA, there was a decrease in SH values in the presence of MB and this decrease was maintained in the I/R group. AST levels were increased in all ischemic with or without MB. Conclusions: The methylene blue was not able to restore the mitochondrial parameters studied. Also, it was able to decrease lipid peroxidation, preventing the formation of reactive oxygen species.
Asunto(s)
Humanos , Animales , Masculino , Daño por Reperfusión/prevención & control , Inhibidores Enzimáticos/uso terapéutico , Hígado/irrigación sanguínea , Azul de Metileno/uso terapéutico , Consumo de Oxígeno , Aspartato Aminotransferasas/sangre , Valores de Referencia , Factores de Tiempo , Mitocondrias Hepáticas/efectos de los fármacos , Mitocondrias Hepáticas/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Daño por Reperfusión/metabolismo , Reproducibilidad de los Resultados , Especies Reactivas de Oxígeno/análisis , Especies Reactivas de Oxígeno/metabolismo , Ratas Wistar , Respiración de la Célula , Alanina Transaminasa/sangre , Inhibidores Enzimáticos/farmacología , Membranas Mitocondriales/efectos de los fármacos , Membranas Mitocondriales/metabolismo , Hígado/metabolismo , Malondialdehído/análisis , Azul de Metileno/farmacología , Dilatación Mitocondrial/efectos de los fármacosRESUMEN
A 57-year-old female patient received elective liver transplant due to nonalcoholic steatohepatitis complicated by hepatocellular carcinoma. Her preoperative Model for End-Stage Liver Disease score was 11. The total transplant ischemic time was 10 hours and 35 minutes, and the warm ischemic time was 35 minutes. Even with aggressive fluid overload and use of high concentrations of vasoactive amines, the patient developed possible primary graft dysfunction with poor response to fluids and vasopressor support, suggesting vasoplegic syndrome. On the basis of the hypothesis of vasoplegic syndrome, the patient received methylene blue intravenously (100 mg bolus for 12 h/1.5 mg/kg). The catastrophic situation was controlled. The patient's urine output markedly improved, she was subsequently weaned from vasoactive support, and mechanical ventilation was discontinued 2 days later. The patient was discharged on the 20th postoperative day.
Asunto(s)
Carcinoma Hepatocelular/cirugía , Neoplasias Hepáticas/cirugía , Trasplante de Hígado/efectos adversos , Azul de Metileno/uso terapéutico , Enfermedad del Hígado Graso no Alcohólico/cirugía , Daño por Reperfusión/tratamiento farmacológico , Choque/tratamiento farmacológico , Carcinoma Hepatocelular/diagnóstico , Femenino , Humanos , Neoplasias Hepáticas/diagnóstico , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Daño por Reperfusión/diagnóstico , Daño por Reperfusión/etiología , Choque/diagnóstico , Choque/etiología , Resultado del Tratamiento , Vasoplejía/tratamiento farmacológico , Vasoplejía/etiologíaRESUMEN
PURPOSE: To analyze the effect of methylene blue (MB) therapy during the liver ischemia-reperfusion injury (I/R) process. METHODS: Thirty-five male Wistar rats were used, (70%) submitted to partial ischemia (IR) or not (NIR) (30%) were obtained from the same animal. These animals were divided into six groups: 1) Sham (SH), 2) Sham with MB (SH-MB); 3) I/R, submitted to 60 minutes of partial ischemia and 15 minutes of reperfusion; 4) NI/R, without I/R obtained from the same animal of group I/R; 5) I/R-MB submitted to I/R and MB and 6) NI/R-MB, without I/R. Mitochondrial function was evaluated. Osmotic swelling of mitochondria as well as the determination of malondialdehyde (MDA) was evaluated. Serum (ALT/AST) dosages were also performed. MB was used at the concentration of 15mg/kg, 15 minutes before hepatic reperfusion. Statistical analysis was done by the Mann Whitney test at 5%. RESULTS: State 3 shows inhibition in all ischemic groups. State 4 was increased in all groups, except the I/R-MB and NI/R-MB groups. RCR showed a decrease in all I/R and NI/R groups. Mitochondrial osmotic swelling showed an increase in all I/R NI/R groups in the presence or absence of MB. About MDA, there was a decrease in SH values in the presence of MB and this decrease was maintained in the I/R group. AST levels were increased in all ischemic with or without MB. CONCLUSIONS: The methylene blue was not able to restore the mitochondrial parameters studied. Also, it was able to decrease lipid peroxidation, preventing the formation of reactive oxygen species.
Asunto(s)
Inhibidores Enzimáticos/uso terapéutico , Hígado/irrigación sanguínea , Azul de Metileno/uso terapéutico , Daño por Reperfusión/prevención & control , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Respiración de la Célula , Inhibidores Enzimáticos/farmacología , Humanos , Peroxidación de Lípido/efectos de los fármacos , Hígado/metabolismo , Masculino , Malondialdehído/análisis , Azul de Metileno/farmacología , Mitocondrias Hepáticas/efectos de los fármacos , Mitocondrias Hepáticas/metabolismo , Membranas Mitocondriales/efectos de los fármacos , Membranas Mitocondriales/metabolismo , Dilatación Mitocondrial/efectos de los fármacos , Consumo de Oxígeno , Ratas Wistar , Especies Reactivas de Oxígeno/análisis , Especies Reactivas de Oxígeno/metabolismo , Valores de Referencia , Daño por Reperfusión/metabolismo , Reproducibilidad de los Resultados , Factores de TiempoRESUMEN
PURPOSE: To assess the effect of two laser wavelengths, either separate or combined, on intact rat livers. METHOD: Nineteen male Wistar rats (200-300 g) were submitted to laser irradiation at 5 different sites on the liver surface.Wavelengths 660 and 780 nm were used, with a dose of irradiation of 60 J/cm2/site.The animals were divided into the groups:control (C) and animals irradiated with 660 nm laser (L1), with 780 nm laser (L2) or withboth wavelengths (L3).Mitochondrial function, mitochondrial swelling, and hepatocellular malondialdehyde (MDA) levels were determined.Data were analyzed by the Mann-Whitney test, with the level of significance set at 5%. RESULTS: There was a reduction of ADP-activated respiration (state 3) in group L1 compared to group C (p=0.0016), whereas the values of group L2 were similar to control.Group L3 also showed a reduction of state 3 (p=0.0159).There was a reduction of RCR in group L1 compared to control (p=0.0001) and to group L2 (p=0.0040).Mitochondrial swelling only differed between group L3 and control (p=0.0286).There was a increase in MDA levels in group L3 compared to control (p=0.0476) and to group L2 (p=0.0286) and in group L1 compared to group L2 (p=0.0132). CONCLUSION: Although laser irradiation reduced mitochondrial function,it did not interfere with the hepatocellular energy status.
Asunto(s)
Láseres de Semiconductores , Hígado/efectos de la radiación , Mitocondrias Hepáticas/efectos de la radiación , Estrés Oxidativo/efectos de la radiación , Animales , Relación Dosis-Respuesta en la Radiación , Terapia por Luz de Baja Intensidad , Masculino , Malondialdehído/análisis , Dilatación Mitocondrial/efectos de los fármacos , Dosis de Radiación , Ratas Wistar , Espectrofotometría , Factores de TiempoRESUMEN
PURPOSE: To assess the effect of two laser wavelengths, either separate or combined, on intact rat livers. METHOD: Nineteen male Wistar rats (200-300 g) were submitted to laser irradiation at 5 different sites on the liver surface.Wavelengths 660 and 780 nm were used, with a dose of irradiation of 60 J/cm2/site.The animals were divided into the groups:control (C) and animals irradiated with 660 nm laser (L1), with 780 nm laser (L2) or withboth wavelengths (L3).Mitochondrial function, mitochondrial swelling, and hepatocellular malondialdehyde (MDA) levels were determined.Data were analyzed by the Mann-Whitney test, with the level of significance set at 5%. RESULTS: There was a reduction of ADP-activated respiration (state 3) in group L1 compared to group C (p=0.0016), whereas the values of group L2 were similar to control.Group L3 also showed a reduction of state 3 (p=0.0159).There was a reduction of RCR in group L1 compared to control (p=0.0001) and to group L2 (p=0.0040).Mitochondrial swelling only differed between group L3 and control (p=0.0286).There was a increase in MDA levels in group L3 compared to control (p=0.0476) and to group L2 (p=0.0286) and in group L1 compared to group L2 (p=0.0132). CONCLUSION: Although laser irradiation reduced mitochondrial function,it did not interfere with the hepatocellular energy status.
Asunto(s)
Animales , Masculino , Mitocondrias Hepáticas/efectos de la radiación , Estrés Oxidativo/efectos de la radiación , Láseres de Semiconductores , Hígado/efectos de la radiación , Dosis de Radiación , Espectrofotometría , Factores de Tiempo , Ratas Wistar , Terapia por Luz de Baja Intensidad , Relación Dosis-Respuesta en la Radiación , Malondialdehído/análisis , Dilatación Mitocondrial/efectos de los fármacosAsunto(s)
Congresos como Asunto/estadística & datos numéricos , Cirugía General/estadística & datos numéricos , Estudiantes de Medicina/estadística & datos numéricos , Investigación Biomédica Traslacional/estadística & datos numéricos , Femenino , Humanos , Masculino , Publicaciones Periódicas como Asunto/estadística & datos numéricos , Distribución por SexoRESUMEN
PURPOSE: To evaluate the effect of the hyperbaric oxygen (HBO) treatment as a pre-conditioning for I/R effects in the liver ischemia. METHODS: Fifty-seven male Wistar rats (260-300g) were submitted to the following procedures: SHAM; I/R, rats submitted to I/R, consisting of partial ischemia of 70% of the liver for 90 minutes followed by 15 minutes of reperfusion; HBO I/R 1 ATA, 30 minutes of HBO treatment at the pressure of 1 absolute atmosphere (ATA) during the ischemia time. HBO I/R 2 ATA, 30 minutes of HBO (2 ATA) during the ischemia time. Pre HBO I/R 30', rats submitted to 30 minutes of HBO (2 ATA) immediately before the I/R time. Pre HBO I/R 90', rats submitted to 90 minutes of HBO (2 ATA) immediately before the I/R time. RESULTS: There was a significant worsening of all the parameters of mitochondrial energy production (state 3, 4, RCR and Swelling) in the I/R group, when compared to the Sham group (I/R Asunto(s)
Oxigenoterapia Hiperbárica/métodos
, Precondicionamiento Isquémico/métodos
, Hígado/irrigación sanguínea
, Daño por Reperfusión/terapia
, Alanina Transaminasa/sangre
, Animales
, Aspartato Aminotransferasas/sangre
, Respiración de la Célula
, Edema/etiología
, Masculino
, Mitocondrias Hepáticas/fisiología
, Enfermedades Mitocondriales/etiología
, Ratas Wistar
, Reproducibilidad de los Resultados
, Factores de Tiempo
, Resultado del Tratamiento
RESUMEN
PURPOSE: To determine the effect of hyperbaric hyperoxia as hepatic preconditioning on hepatocellular integrity in rats submitted to intermittent hepatic ischemia/reperfusion injury. METHODS: Twenty male Wistar rats were divided into 4 groups (SHAM, I/R, HBO-I/R and CONTROL). The surgical technique consisted of total clamping of the hepatic pedicle for 15 min, followed by reperfusion for 5 min, performed twice. The application of hyperbaric oxygen (HBO) was carried out in a collective chamber (simultaneous exposure of 4 rats) pressurized directly with oxygen at 2 ATA for 60 min. Tissue malondialdehyde (MDA) levels were determined and blood samples were collected for the determination of serum AST and ALT levels. Data were analyzed statistically by the Mann-Whitney test, with the level of significance set at p < 0.05. RESULTS: A statistically significant difference in MDA (p< 0.05) was observed between control and HBO-I/R, but not between control and I/R. Regarding AST, there was a difference between control and I/R and HBO-I/R. Analysis of ALT revealed a significant difference between control and I/R (p<0.05) and between I/R and HBO-I/R, with no difference between control and HBO-IR. CONCLUSION: Hyperoxic preconditioning proved to be favorable regarding alanine transaminase, but not aspartate aminotranserase or malondialdehyde levels.
Asunto(s)
Oxigenoterapia Hiperbárica/métodos , Precondicionamiento Isquémico/métodos , Hígado/irrigación sanguínea , Daño por Reperfusión/terapia , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Masculino , Malondialdehído/análisis , Mitocondrias Hepáticas/fisiología , Ratas Wistar , Reproducibilidad de los Resultados , Factores de Tiempo , Resultado del TratamientoRESUMEN
PURPOSE: To evaluate the effects of hyperbaric oxygen on rats submitted to hepatic ischemia and reperfusion. METHODS: Twenty-three Wistar rats were divided at random into 3 groups: SHAM, rats submitted to surgical and anesthetic stress without induction of hepatic ischemia/reperfurion; I/R, rats submitted to total ischemia of the hepatic pedicle for 25 min followed by 5 min of reperfusion; HBOI/R, rats submitted to 60 min of hyperbaric oxygen therapy at a pressure of 2 absolute atmospheres immediately after the experimental protocol of ischemia/reperfusion. Hepatic function was evaluated by quantitation of serum alanine aminotranferase (ALT) and aspartate aminotransferase (AST), and by mitochondrial function through the determination of states 3 and 4 of mitochondrial respiration, respiratory control ratio (RCR) and mitochondrial swelling. Data were analyzed by the Mann-Whitney test, with the level of significance set at p <0.05. RESULTS: There was a significant difference in state 3 values for the SHAM group vs I/R and I/R vs IRHBO, in state 4 values for the SHAM group vs I/R; and in mitochondrial swelling for the SHAM groups vs I/RHBO, SHAM vs I/R, and IR vs I/RHBO. CONCLUSION: The use of hyperbaric oxygen after I/R improved in a relative manner both the production of energy and the effects on the mitochondrial wall.
Asunto(s)
Oxigenoterapia Hiperbárica/métodos , Hígado/irrigación sanguínea , Daño por Reperfusión/terapia , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Respiración de la Célula , Masculino , Mitocondrias Hepáticas/fisiología , Distribución Aleatoria , Ratas Wistar , Reproducibilidad de los Resultados , Factores de Tiempo , Resultado del TratamientoRESUMEN
PURPOSE: To evaluate the effects of hyperbaric oxygen on rats submitted to hepatic ischemia and reperfusion. METHODS: Twenty-three Wistar rats were divided at random into 3 groups: SHAM, rats submitted to surgical and anesthetic stress without induction of hepatic ischemia/reperfurion; I/R, rats submitted to total ischemia of the hepatic pedicle for 25 min followed by 5 min of reperfusion; HBOI/R, rats submitted to 60 min of hyperbaric oxygen therapy at a pressure of 2 absolute atmospheres immediately after the experimental protocol of ischemia/reperfusion. Hepatic function was evaluated by quantitation of serum alanine aminotranferase (ALT) and aspartate aminotransferase (AST), and by mitochondrial function through the determination of states 3 and 4 of mitochondrial respiration, respiratory control ratio (RCR) and mitochondrial swelling. Data were analyzed by the Mann-Whitney test, with the level of significance set at p <0.05. RESULTS: There was a significant difference in state 3 values for the SHAM group vs I/R and I/R vs IRHBO, in state 4 values for the SHAM group vs I/R; and in mitochondrial swelling for the SHAM groups vs I/RHBO, SHAM vs I/R, and IR vs I/RHBO. CONCLUSION: The use of hyperbaric oxygen after I/R improved in a relative manner both the production of energy and the effects on the mitochondrial wall. .
Asunto(s)
Animales , Masculino , Oxigenoterapia Hiperbárica/métodos , Hígado/irrigación sanguínea , Daño por Reperfusión/terapia , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Respiración de la Célula , Mitocondrias Hepáticas/fisiología , Distribución Aleatoria , Ratas Wistar , Reproducibilidad de los Resultados , Factores de Tiempo , Resultado del TratamientoRESUMEN
PURPOSE: To determine the effect of hyperbaric hyperoxia as hepatic preconditioning on hepatocellular integrity in rats submitted to intermittent hepatic ischemia/reperfusion injury. METHODS: Twenty male Wistar rats were divided into 4 groups (SHAM, I/R, HBO-I/R and CONTROL). The surgical technique consisted of total clamping of the hepatic pedicle for 15 min, followed by reperfusion for 5 min, performed twice. The application of hyperbaric oxygen (HBO) was carried out in a collective chamber (simultaneous exposure of 4 rats) pressurized directly with oxygen at 2 ATA for 60 min. Tissue malondialdehyde (MDA) levels were determined and blood samples were collected for the determination of serum AST and ALT levels. Data were analyzed statistically by the Mann-Whitney test, with the level of significance set at p < 0.05. RESULTS: A statistically significant difference in MDA (p< 0.05) was observed between control and HBO-I/R, but not between control and I/R. Regarding AST, there was a difference between control and I/R and HBO-I/R. Analysis of ALT revealed a significant difference between control and I/R (p<0.05) and between I/R and HBO-I/R, with no difference between control and HBO-IR. CONCLUSION: Hyperoxic preconditioning proved to be favorable regarding alanine transaminase, but not aspartate aminotranserase or malondialdehyde levels. .
Asunto(s)
Animales , Masculino , Oxigenoterapia Hiperbárica/métodos , Precondicionamiento Isquémico/métodos , Hígado/irrigación sanguínea , Daño por Reperfusión/terapia , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Malondialdehído/análisis , Mitocondrias Hepáticas/fisiología , Ratas Wistar , Reproducibilidad de los Resultados , Factores de Tiempo , Resultado del TratamientoRESUMEN
PURPOSE: To evaluate the effect of the hyperbaric oxygen (HBO) treatment as a pre-conditioning for I/R effects in the liver ischemia. METHODS: Fifty-seven male Wistar rats (260-300g) were submitted to the following procedures: SHAM; I/R, rats submitted to I/R, consisting of partial ischemia of 70% of the liver for 90 minutes followed by 15 minutes of reperfusion; HBO I/R 1 ATA, 30 minutes of HBO treatment at the pressure of 1 absolute atmosphere (ATA) during the ischemia time. HBO I/R 2 ATA, 30 minutes of HBO (2 ATA) during the ischemia time. Pre HBO I/R 30', rats submitted to 30 minutes of HBO (2 ATA) immediately before the I/R time. Pre HBO I/R 90', rats submitted to 90 minutes of HBO (2 ATA) immediately before the I/R time. RESULTS: There was a significant worsening of all the parameters of mitochondrial energy production (state 3, 4, RCR and Swelling) in the I/R group, when compared to the Sham group (I/R <Sham, p<0.05). There was also a significant worsening in state 4, RCR and mitochondrial edema in the Pre HBO I/R 90' group compared to the I/R group. Hepatic enzyme concentrations were significantly higher in the I/R group. CONCLUSION: The use of hyperbaric oxygen before and during I/R did not improve the production of hepatocellular energy reduced by I/R, nor did it prevent the installation of mitochondrial edema induced by Iischemia/reperfusion. .