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1.
N Engl J Med ; 376(21): 2021-2031, 2017 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-28320259

RESUMO

BACKGROUND: Acute left ventricular dysfunction is a major complication of cardiac surgery and is associated with increased mortality. Meta-analyses of small trials suggest that levosimendan may result in a higher rate of survival among patients undergoing cardiac surgery. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled trial involving patients in whom perioperative hemodynamic support was indicated after cardiac surgery, according to prespecified criteria. Patients were randomly assigned to receive levosimendan (in a continuous infusion at a dose of 0.025 to 0.2 µg per kilogram of body weight per minute) or placebo, for up to 48 hours or until discharge from the intensive care unit (ICU), in addition to standard care. The primary outcome was 30-day mortality. RESULTS: The trial was stopped for futility after 506 patients were enrolled. A total of 248 patients were assigned to receive levosimendan and 258 to receive placebo. There was no significant difference in 30-day mortality between the levosimendan group and the placebo group (32 patients [12.9%] and 33 patients [12.8%], respectively; absolute risk difference, 0.1 percentage points; 95% confidence interval [CI], -5.7 to 5.9; P=0.97). There were no significant differences between the levosimendan group and the placebo group in the durations of mechanical ventilation (median, 19 hours and 21 hours, respectively; median difference, -2 hours; 95% CI, -5 to 1; P=0.48), ICU stay (median, 72 hours and 84 hours, respectively; median difference, -12 hours; 95% CI, -21 to 2; P=0.09), and hospital stay (median, 14 days and 14 days, respectively; median difference, 0 days; 95% CI, -1 to 2; P=0.39). There was no significant difference between the levosimendan group and the placebo group in rates of hypotension or cardiac arrhythmias. CONCLUSIONS: In patients who required perioperative hemodynamic support after cardiac surgery, low-dose levosimendan in addition to standard care did not result in lower 30-day mortality than placebo. (Funded by the Italian Ministry of Health; CHEETAH ClinicalTrials.gov number, NCT00994825 .).


Assuntos
Baixo Débito Cardíaco/tratamento farmacológico , Procedimentos Cirúrgicos Cardíacos , Cardiotônicos/uso terapêutico , Hemodinâmica/efeitos dos fármacos , Hidrazonas/uso terapêutico , Mortalidade , Piridazinas/uso terapêutico , Idoso , Cardiotônicos/administração & dosagem , Cardiotônicos/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Hidrazonas/administração & dosagem , Hidrazonas/efeitos adversos , Infusões Intravenosas , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Período Perioperatório , Complicações Pós-Operatórias/tratamento farmacológico , Piridazinas/administração & dosagem , Piridazinas/efeitos adversos , Respiração Artificial , Simendana , Volume Sistólico/efeitos dos fármacos , Falha de Tratamento
2.
Nanomedicine ; 15(1): 37-46, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30240826

RESUMO

Unmodified hydrated С60 fullerene molecules (C60UHFM) were shown to reduce the formation ROS in water and 8-oxoguanine in DNA upon ionizing radiation impact. C60UHFM efficiently eliminate long-lived protein radicals arising after irradiation. In irradiated mice C60UHFM reduce the rate of single/double-strand DNA breaks and amount of chromosomal breaks. The radioprotective activity of C60UHFM was estimated by the survival rate of animals; the dose modification factor for animal survival was 1.3. Hematological tests showed that C60UHFM injection in mice prior to irradiation results in a decrement of irradiation-induced leucopenia and thrombocytopenia. Histological analysis testified that C60UHFM provide significant protection of small intestine tissues in mice against irradiation-induced damage. The obtained data assume that the radioprotective properties of C60UHFM are determined by their antioxidant, antiradical and DNA-protective qualities. Thus, it was demonstrated that C60UHFM are a novel antioxidant and radioprotective agent capable of substantial reduction of the harmful effects of ionizing radiation.


Assuntos
Antioxidantes/farmacologia , Dano ao DNA , Fulerenos/farmacologia , Estresse Oxidativo , Proteínas/química , Protetores contra Radiação/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Animais , Masculino , Camundongos , Camundongos Pelados , Radiação Ionizante
3.
J Cardiothorac Vasc Anesth ; 31(6): 2080-2085, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28967626

RESUMO

OBJECTIVE: To measure the release of plasma nuclear deoxyribonucleic acid (DNA) and to assess the relationship between nuclear DNA level and acute kidney injury occurrence in patients undergoing cardiac surgery. SETTING: Cardiovascular anesthesiology and intensive care unit of a large tertiary-care university hospital. DESIGN: Prospective observational study. PARTICIPANTS: Fifty adult patients undergoing cardiac surgery. INTERVENTIONS: Nuclear DNA concentration was measured in the plasma. The relationship between the level of nuclear DNA and the incidence of acute kidney injury after coronary artery bypass grafting was investigated. MEASUREMENTS AND MAIN RESULTS: Cardiac surgery leads to significant increase in plasma nuclear DNA with peak levels 12 hours after surgery (median [interquartile range] 7.0 [9.6-22.5] µg/mL). No difference was observed between off-pump and on-pump surgical techniques. Nuclear DNA was the only predictor of acute kidney injury between baseline and early postoperative risk factors. CONCLUSIONS: The authors found an increase of nuclear DNA in the plasma of patients who had undergone coronary artery bypass grafting, with a peak after 12 hours and an association of nuclear DNA with postoperative acute kidney injury.


Assuntos
Injúria Renal Aguda/sangue , Injúria Renal Aguda/diagnóstico , Ponte de Artéria Coronária/efeitos adversos , DNA/sangue , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/diagnóstico , Injúria Renal Aguda/etiologia , Idoso , Ponte de Artéria Coronária/tendências , Humanos , Pessoa de Meia-Idade , Projetos Piloto , Complicações Pós-Operatórias/etiologia , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco
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