Browsing by Author "Rebolledo Acevedo, Rolando Arturo"

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    Anti-Apoptotic Effects of 3,3’,5-Triiodo-L-Thyronine in the Liver of Brain-Dead Rats
    (2015) Rebolledo Acevedo, Rolando Arturo; Van Erp, Anne C.; Ottens, Petra J.; Wiersema-Buist, Janneke; Leuvenink, Henri G. D.; Romanque, Pamela
    Background: Thyroid hormone treatment in brain-dead organ donors has been extensively studied and applied in the clinical setting. However, its clinical applicability remains controversial due to a varying degree of success and a lack of mechanistic understanding about the therapeutic effects of 3,3’,5-Triiodo-L-thyronine (T3). T3 pre-conditioning leads to anti-apoptotic and pro-mitotic effects in liver tissue following ischemia/reperfusion injury. Therefore, we aimed to study the effects of T3 pre-conditioning in the liver of brain-dead rats. Methods: Brain death (BD) was induced in mechanically ventilated rats by inflation of a Fogarty catheter in the epidural space. T3 (0.1 mg/kg) or vehicle was administered intraperitoneally 2 h prior to BD induction. After 4 h of BD, serum and liver tissue were collected. RT-qPCR, routine biochemistry, and immunohistochemistry were performed. Results: Brain-dead animals treated with T3 had lower plasma levels of AST and ALT, reduced Bax gene expression, and less hepatic cleaved Caspase-3 activation compared to brain-dead animals treated with vehicle. Interestingly, no differences in the expression of inflammatory genes (IL-6, MCP-1, IL-1β) or the presence of pro-mitotic markers (Cyclin-D and Ki-67) were found in brain-dead animals treated with T3 compared to vehicle-treated animals. Conclusion: T3 pre-conditioning leads to beneficial effects in the liver of brain-dead rats as seen by lower cellular injury and reduced apoptosis, and supports the suggested role of T3 hormone therapy in the management of brain-dead donors.
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    Chilean experience in liver transplantation for acute liver failure in children
    (2010) Uribe, M.; Alba, A.; Hunter, B.; Valverde, C.; Godoy, J.; Ferrario, M.; Buckel, E.; Cavallieri, S.; Rebolledo Acevedo, Rolando Arturo; Herzog, C.; Calabrán, L.; Flores, L.; Soto, P.
    Background: Acute liver failure (ALF) in children is a life-threatening condition, associated with high mortality, and in almost one third of the cases, with no other therapeutic option than orthotopic liver transplant (OLT). The aim of this study was to present our experience with OLT for ALF in pediatric patients in Chile. Patients fulfilling the criteria for ALF who were transplanted in our centers were prospectively included in an excel Microsoft database. We analyzed demographics, etiology, surgical techniques, complications, and long-term results. Patients and Methods: Between 1994 and 2009, we transplanted 52 pediatric patients with ALF. The most frequent known etiology was acute hepatitis A in 9 cases (18%), but in 26 cases (50%) it was impossible to determine the etiology. Thirty- one patients were males (63%). The overall mean age was 7.5 years and the mean weight, 28.1 kg. Thirty-five (67%) received a cadaveric graft. Among them in 18 cases (34%) the liver had to be reduced but 17 (33%) received whole livers. There were 17 (33%) recipients of living-related livers. Twenty-two patients needed reoperation, including 13 due to surgical complications (59%) and 9 (41%) as planned interventions. Ten patients were retransplanted. Results: Actuarial survival of patients at 1 year was 80% and at 5 and 10 years, 72%. Graft survival at 1 year was 79%, at 5 years 69%, and at 10 years 50%. Conclusion: We have reported a series of pediatric liver transplant patients due to ALF whose results were comparable to other reported series. Living donor transplantation for ALF should be considered and offers a low morbidity rate without mortality.
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    ESICM LIVES 2016: part two
    (2016) Alegría Aguirre, Luz Katiushka; Soto, D.; Jarufe Cassis, Nicolás; Bruhn, Alejandro; Castro López, Ricardo; Kattan Tala, Eduardo José; Rebolledo Acevedo, Rolando Arturo; Achurra Tirado, Pablo; Bakker, Jan; Hernández P., Glenn
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    Implementación de un modelo porcino de trasplante hepático en Chile
    (Sociedad de Cirujanos de Chile, 2020) Ochoa, Gabriela; Marino, Carlo; Riveros, Sergio; Morales, Emilio; Jarry, Cristian; Viñuela, Macarena; Alegría, Leyla; Zenteno, María Josefina; Martínez Castillo, Jorge; Achurra Tirado, Pablo; Rebolledo Acevedo, Rolando Arturo
    Objetivo: Presentar la implementación del primer modelo porcino de trasplante hepático (TH) en Chile y sus resultados. Material y Método: Se implementó un protocolo quirúrgico y anestésico en el contextode una investigación en perfusión normotérmica hepática financiada por un Fondo Nacional de Desarrollo Científico y Tecnológico. Los cerdos fueron seleccionados por peso (35-40 kilos), en cada experimentose utilizó dos, donante y receptor, sometidos a procura y trasplante respectivamente. El análisis se realizó con estadística descriptiva. Resultados: Se realizaron 26 experimentos (marzo de 2018-octubre de 2019). El protocolo consta de 7 etapas: Preparación, Instrumentalización, Procura o Hepatectomía, Tiempo Anhepático, Etapa de Isquemia-Reperfusión, Monitorización y Eutanasia. Las primeras tres son similares en ambos cerdos, y desde la cuarta en adelante corresponde sólo al receptor. La supervivencia a la cirugíafue de 92,3% (24/26) y al seguimiento de 76,9% (20/26). La mortalidad se produjo por inestabilidad cardiovascular postreperfusión portal. El tiempo quirúrgico promedio fue de 170 min, y el tiempo anhepático de 33 min. La PAM cursó una baja postreperfusión con recuperación al final de la monitorización (67,4 mmHg media) y la tendencia en ph fue a acidosis al final del seguimiento (7,21 media). Se requirió drogas vasoactivas en 12 casos. Discusión: Logramos implementar un modelo experimental simplificado y reproducible de TH sin necesidad de circulación extracorpórea ni puente veno-venoso gracias a la estandarización de la técnica quirúrgica y de los cuidados perioperatorios. Conclusiones: La consolidación de un modelo experimental significa el primer paso en investigación preclínica de nuevas tecnologías asociadas al TH en Chile.
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    Inadequate Antioxidative Responses in Kidneys of Brain-Dead Rats
    (2017) Hoeksma, D.; Rebolledo Acevedo, Rolando Arturo; Hottenrott, M.; Bodar, Y.; Wiersema-Buist, J.; Van Goor, H.; Leuvenink, H.
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    Intraabdominal hypertension in patients with septic shock
    (Southeastern Surgical Congress, 2007) Regueira, Tomás; Hasbún, Pablo; Rebolledo Acevedo, Rolando Arturo; Galindo, José; Aguirre, Marcia; Romero, Carlos; Castillo, Luis; Bugedo Tarraza, Guillermo; Hernández P., Glenn
    Intraabdominal hypertension (IAH) develops frequently in patients with septic shock. Even a moderate increase in intraabdominal pressure (IAP) in this setting could be associated with high lactate levels. The authors conducted a prospective, observational, nonrandomized control trial in the surgical intensive care unit of an academic tertiary center. Twenty-seven patients with septic shock (septic shock group), and 19 patients undergoing abdominal surgery with more than two risk factors for IAH (postoperative control group) were admitted consecutively to the intensive care unit. IAP was measured every 6 hours during the first 48 hours. IAH was diagnosed with two consecutive measurements greater than 20 mm Hg. The main outcome measures were prevalence of IAH in septic shock and control groups; and comparative lactate levels, norepinephrine requirements and organ dysfunctions in patients with and without IAH in both groups. Fifty-one per cent of patients with septic shock and 31 per cent of control patients developed IAH. Patients with septic shock with and without IAH were comparable in peak norepinephrine dose, sequential organ failure assessment score, and mortality. However, peak lactate levels were significantly higher in patients with septic shock and IAH compared with those without IAH (3.5 mmol/L versus 1.9 mmol/L, P < 0.04). There was a significant positive temporal correlation between IAP and lactate levels in patients with septic shock with IAH. Peak levels of both occurred early and decreased progressively over time. Control patients with and without IAH exhibited comparable peak lactate levels. Intraabdominal hypertension is very common in septic shock and appears to be related to high lactate levels, which diminish as IAP decreases. Future studies should address the usefulness of IAP monitoring in patients with septic shock.
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    Liver transplantation in children weighing less than 10 kg.: chilean experience
    (2013) Uribe, M.; Alba, A.; Hunter, B.; González, G.; Godoy, J.; Ferrario, M.; Buckel, E.; Cavallieri, S.; Heine, C.; Rebolledo Acevedo, Rolando Arturo; Auad, H.; Acuña, C.
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    Pediatric liver transplantation experience and outcome in Chile
    (2013) Acuña, C.; Zuleta, R.; Dalmazzo, R.; Valverde, C.; Uribe, M.; Alba, A.; Buckel, E.; Hunter, B.; González, G.; Godoy, J.; Ferrario, M.; Cavallieri, S.; Campos, M.; Pizarro, F.; Wash, A.; Ferrón, S.; Díaz, V.; Macho, L.; Herzog, C.; Calabrán, L.; Flores, L.; Soto, P.; Heine, C.; Rebolledo Acevedo, Rolando Arturo; Auad, H.
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    Prednisolone has a positive effect on the kidney but not on the liver of brain dead rats: a potencial role in complement activation
    (2014) Rebolledo Acevedo, Rolando Arturo; Liu, Bo; Akhtar, Mohammed Z.; Ottens, Petra J.; Zhang, Jian-Ning; Ploeg, Rutger J.; Leuvenink, Henri G. D.
    Background: Contradictory evidence has been published on the effects of steroid treatments on the outcomes of kidney and liver transplantation from brain dead (BD) donors. Our study aimed to evaluate this disparity by investigating the effect of prednisolone administration on BD rats. Methods: BD induction was performed in ventilated rats by inflating a Fogarty catheter placed in the epidural space. Prednisolone (22.5 mg/kg) was administered 30 min prior to BD induction. After four hours of determination of BD: serum, kidney and liver tissues samples were collected and stored. RT-qPCR, routine biochemistry and immunohistochemistry were performed. Results: Prednisolone treatment reduced circulating IL-6 and creatinine plasma levels but not serum AST, ALT or LDH. Polymorphonuclear influx assessed by histology, and inflammatory gene expression were reduced in the kidney and liver. However, complement component 3 (C3) expression was decreased in kidney but not in liver. Gene expression of HSP-70, a cytoprotective protein, was down-regulated in the liver after treatment. Conclusions: This study shows that prednisolone decreases inflammation and improves renal function, whilst not reducing liver injury. The persistence of complement activation and the negative effect on protective cellular mechanisms in the liver may explain the disparity between the effects of prednisolone on the kidney and liver of BD rats. The difference in the molecular and cellular responses to prednisolone administration may explain the contradictory evidence of the effects of prednisolone on different organ types from brain dead organ donors.
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    Steroid Anti-Inflammatory Effects Did Not Improve Organ Quality in Brain-Dead Rats
    (2015) Rebolledo Acevedo, Rolando Arturo; Liu, Bo; Akhtar, Mohammed Z.; Ottens, Petra J.; Zhang, Jian-Ning; Ploeg, Rutger J.; Leuvenink, Henri G. D.
    Effect of glucocorticoid administration on improving the outcomes of kidney and liver allografts has not been clearly elucidated. This study investigated the effect of prednisolone administration after onset of brain death (BD) on kidney and liver in a controlled rat model of BD. BD was induced in rats by inflating an epidurally placed balloon catheter. Animals were treated with saline or prednisolone (5, 12.5, or 22.5 mg/kg) one hour after the onset of BD. After 4 hours of BD, experiments were terminated and serum and tissues were collected. Tissue gene and protein expression were measured for markers of inflammation, apoptosis, and cellular stress response markers. Prednisolone caused a reduction of plasma levels of IL-6, while the tissue expression of IL-6, IL-1β, and MCP-1 in both kidney and liver were also reduced. Creatinine plasma levels, complement (C3) expression, HSP-70, HO-1, Bcl2/BAX ratio, and PMN influx did not significantly change in kidney nor liver. Plasma AST and LDH levels were increased in the prednisolone treated group. Our results demonstrate prednisolone can has an anti-inflammatory effect mediated through reducing serum circulating cytokines. However, this anti-inflammatory effect does not translate into improved kidney function and indeed was associated with increased liver injury markers.
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    The Crosstalk between ROS and Autophagy in the Field of Transplantation Medicine
    (2017) Van Erp, Anne C.; Hoeksma, Dane; Rebolledo Acevedo, Rolando Arturo; Ottens, Petra J.; Jochmans, Ina; Monbaliu, Diethard; Pirenne, Jacques; Leuvenink, Henri G. D.; Decuypere, Jean Paul
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    Using an Integrated-Omics Approach to Identify Key Cellular Processes That Are Disturbed in the Kidney After Brain Death
    (2016) Akhtar, M. Z.; Huang, H.; Kaisar, M.; Lo Faro, M. L.; Rebolledo Acevedo, Rolando Arturo; Morten, K.; Heather, L. C.; Dona, A.; Leuvenink, H. G.; Fuggle, S. V.; Kessler, B. M.; Pugh, C. W.; Ploeg, R. J.
    In an era where we are becoming more reliant on vulnerable kidneys for transplantation from older donors, there is an urgent need to understand how brain death leads to kidney dysfunction and, hence, how this can be prevented. Using a rodent model of hemorrhagic stroke and next-generation proteomic and metabolomic technologies, we aimed to delineate which key cellular processes are perturbed in the kidney after brain death. Pathway analysis of the proteomic signature of kidneys from brain-dead donors revealed large-scale changes in mitochondrial proteins that were associated with altered mitochondrial activity and morphological evidence of mitochondrial injury. We identified an increase in a number of glycolytic proteins and lactate production, suggesting a shift toward anaerobic metabolism. Higher amounts of succinate were found in the brain death group, in conjunction with increased markers of oxidative stress. We characterized the responsiveness of hypoxia inducible factors and found this correlated with post-brain death mean arterial pressures. Brain death leads to metabolic disturbances in the kidney and alterations in mitochondrial function and reactive oxygen species generation. This metabolic disturbance and alteration in mitochondrial function may lead to further cellular injury. Conditioning the brain-dead organ donor by altering metabolism could be a novel approach to ameliorate this brain death-induced kidney injury.