Effects of hexafluoro-2-propanol on normothermal liver ischemia and reperfusion injury in rats

Introdução: Um dos principais problemas clínicos após o transplante de fígado e ressecções hepáticas é a disfunção hepática decorrente da lesão de isquemia e reperfusão. Várias estratégias têm sido implementadas para diminuir a lesão de IR. Recentes estudos experimentais demonstraram efeitos protetores em tecidos com o uso dos metabolitos do sevoflurano, relacionados, principalmente, aos grupos estruturais de carbono trifluorinado. A nossa hipótese é que a administração endovenosa do metabólito hexafluoro-2-propanol diminui a lesão de isquemia reperfusão hepática. Objetivo: Avaliar os efeitos da administração hexafluoro-2-propanol em modelo experimental de lesão de isquemia e reperfusão hepática normotérmica. Métodos: Vinte e quatro ratos Wistar machos foram divididos em 3 grupos: grupo controle (n=8), animais submetidos a laparotomia mediana com isquemia hepatica parcial por 30 minutos seguida de um período de 4 horas de reperfusão sem administração intravenosa de HFIP; grupo HFIP pré-isquemia (n=8), animais submetidos a laparotomia mediana com isquemia hepatica parcial por 30 minutos seguida de um período de 4 horas de reperfusão com administração intravenosa de 67mg/kg 5 minutos antes do início da isquemia; grupo HFIP pré-reperfusão (n=8), animais submetidos a laparotomia mediana com isquemia hepatica parcial por 30 minutos seguida de um período de 4 horas de reperfusão com administração intravenosa de 67mg/kg 5 minutos antes do início da reperfusão. Após 4 horas de reperfusao, foram coletadas amostras para análise nos três grupos e registrados dados hemodinâmicos como frequência cardíaca, pressão arterial sistêmica e fluxo portal. Nas amostras coletadas, foram realizadas as dosagens das transaminases AST e ALT, gasometria, interleucinas IL-1beta, IL-6, IL-10 e IL12p70 e TNF-, HMGB-1, determinação da concentração de malondialdeído no tecido hepático e a analise histologica do figado isquemico. Resultados: Apos 4 horas de reperfusao, os niveis sericos de AST foram significativamente menores no grupo HFIP-PR (1.672 ± 879 UI/L) em comparação com os grupos Controle (3.876 ± 2.034 UI/L, p=0,0138) e HFIP-PI (3.723 ± 2.352 UI/L, p=0,0366). Similar comportamento foi evidenciado nos níveis séricos de ALT, com valores menores no grupo HFIP-PR (1596 ± 924 UI/L) em comparação com os grupos Controle (3891 ± 2122 UI/L, p=0,0141) e no grupo HFIP-PI (3437 ± 1561, p=0,0124). Os níveis de HMGB-1 foram menores no grupo HFIP-PR quando comparado ao grupo HFIP-PI (826,5 589,4 pg/mL, 1450 637,4 pg/mL, respectivamente; p= 0,0308). A IL-6 foi maior no grupo HFIP-PI (3571 ± 3376 pg/mL) em comparação ao grupo-controle (1178 ± 1661 pg/mL; p=0,0468). Foi evidenciado um valor menor do pH no grupo HFIP-PI (7,215 ± 0,1217 UI/L) comparado com o grupo-controle (7,329 ± 0,07240 UI/L; p=0,00269). Não foram encontradas diferenças nos graus de necrose na avaliação histológica. Conclusão: A administração intravenosa de HFIP diminuiu a lesão de isquemia reperfusão hepática normotérmica mostrando melhor perfil inflamatório nos ratos tratados com o metabólitoIntroduction: One of the main clinical problems after liver transplantation and liver resections is liver dysfunction resulting from ischemia and reperfusion injury. Several strategies have been implemented to reduce IR injury. Recent experimental studies have demonstrated protective effects on tissues with the use of sevoflurano metabolites, mainly related to the trifluorinated carbon structural groups. Our hypothesis is that the intravenous administration of the metabolite hexafluoro-2-propanol decreases the hepatic ischemia reperfusion injury. Objective: To evaluate the effects of hexafluoro-2-propanol administration in an experimental model of normothermic hepatic ischemia-reperfusion injury. Methods: Twenty-four male Wistar rats were divided into 3 groups: control group (n=8), animals submitted to median laparotomy with partial hepatic ischemia for 30 minutes followed by a period of 4 hours of reperfusion without intravenous administration of HFIP; HFIP pre-ischemia group (n=8), animals submitted to median laparotomy with partial hepatic ischemia for 30 minutes followed by a 4-hour period of reperfusion with intravenous administration of 67mg/kg 5 minutes before the onset of ischemia; HFIP pre-reperfusion group (n=8), animals submitted to median laparotomy with partial hepatic ischemia for 30 minutes followed by a 4-hour period of reperfusion with intravenous administration of 67mg/kg 5 minutes before the start of reperfusion. After 4 hours of reperfusion, samples were collected for analysis in the three groups and hemodynamic data such as heart rate, systemic blood pressure and portal flow were recorded. In the samples collected, dosages of transaminases AST and ALT, blood gases, interleukins IL-1beta, IL-6, IL-10 and IL12p70 and TNF-, HMGB-1, determination of malondialdehyde concentration in liver tissue and histological analysis were performed of the ischemic liver. Results: After 4 hours of reperfusion, serum AST levels were significantly lower in the HFIP-PR group (1,672 ± 879 UI/L) compared to the Control (3,876 ± 2,034 UI/L, p=0.0138) and HFIP-PI (3,723 ± 2,352 UI/L, p=0.0366). Similar behavior was evidenced in serum ALT levels, with lower values in the HFIP-PR group (1596 ± 924 UI/L) compared to the Control groups (3891 ± 2122 UI/L, p=0.0141) and in the HFIP group -PI (3437 ± 1561, p=0.0124). HMGB-1 levels were lower in the HFIP-PR group when compared to the HFIP-PI group (826.5 ± 589.4 pg/mL, 1450 ± 637.4 pg/mL respectively; p= 0.0308). IL-6 was higher in the HFIP-PI group (3571 ± 3376 pg/mL) compared to the control group (1178 ± 1661 pg/mL; p=0.0468). A lower pH value was observed in the HFIP- group PI (7.215 ± 0.1217 UI/L) compared with the control group (7.329 ± 0.07240 UI/L; p=0.00269). No differences were found in the grading of necrosis in the histological evaluation. Conclusion: Intravenous administration of HFIP decreased the normothermic hepatic ischemia reperfusion injury, showing a better inflammatory profile in rats treated with the metabolit

Trasplantes y donación de órganos, un potencial daño colateral en medio de la pandemia por COVID-19

La aparición del nuevo coronavirus a finales de 2019 (COVID-19) y su rápida expansión de mane ra globalizada, ha provocado que muchos sistemas de salud en el mundo sobrepasen su capacidad para atender a los pacientes afectados con la infección de este virus (SARS-Cov2), ocacionando una saturación de los diferentes servicios hospitalarios, incluyendo las unidades de cuidados intensivos (UCIs)

Creatinine-lactate score predicts mortality in non-acetaminophen-induced acute liver failure in patients listed for liver transplantation

Abstract Background The aim of this study was to analyze prognostic indicators of in-hospital mortality among patients listed for urgent liver transplantation (LT) for non-acetaminophen (APAP)-induced acute liver failure (ALF). Methods ALF patients listed for LT according to the King’s College Criteria were retrospectively reviewed. Variables were recorded from medical records and electronic databases (HCMED and RedCap). Results The study included 100 patients, of which 69 were subject to LT and 31 died while waiting for LT. Patients were 35.5 ± 14.73 years old, and 78% were females. The main etiologies were virus (17%), drug-induced (32%), autoimmune (15%), and indeterminate hepatitis (31%). The prioritization-to-LT time interval was 1.5 days (0–9). The non-LT patients showed higher lactate (8.71 ± 5.36 vs. 4.48 ± 3.33 mmol/L), creatinine (229 ± 207 vs. 137 ± 136 µm/L), MELD (44 ± 8 vs. 38 ± 8), and BiLE scores (15.8 ± 5.5 vs. 10.3 ± 4.1) compared to LT patients (p < 0.05). Multiple logistic regression analysis identified creatinine and lactate as independent prognostic factors, and a creatinine-lactate (CL) score was developed. ROC analysis showed that creatinine, lactate, MELD, BiLE, and CL scores had considerable specificity (71–88%), but only BiLE, lactate, and CL presented high sensitivities (70%, 80%, and 87% respectively). AUCs were 0.696 for creatinine, 0.763 for lactate, 0.697 for MELD, 0.814 for BiLE, and 0.835 for CL. Conclusions CL and BiLE scores predict mortality with more accuracy than MELD in patients with ALF during prioritization time. Creatinine and lactate are independent prognostic factors for mortality