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Anesthetic Management and Remote Reperfusion Injuries

13 de outubro de 2011 atualizado por: National Taiwan University Hospital

The Effects of Anesthetic Management on Oxidative Injuries After Cardiopulmonary Bypass

Ischemia- reperfusion ( IR ) injuries were not only seen in the transplanted organs but also the remote organs such as lungs that brings major postoperative complications. Severe complications such as pulmonary infiltration and pulmonary edema following reperfusion were frequently associated with liver transplantation. Cardiac surgery performed with the use of cardiopulmonary bypass ( CPB ) provokes a systemic inflammatory response syndrome that affects postoperative pulmonary, myocardiac and renal functions. Previous study about the reperfusion injuries was focused on the leukocyte and endothelial activation and the following oxidative injuries, however, the alteration on pulmonary function such as dynamic compliance and the oxidative/antioxidative balance in erythrocytes and the following effects in CPB have not been fully studied. Erythrocytes' reaction to oxidative stress including cytoplasma and cell membrane should be studied because RBCs are the major circulating blood cells having different types of antioxidant system to capture reactive oxygen species ( ROS ) thus RBC may be severely injured by ROS or protected ROS injuries during CPB. In these three-year study, we plan to explore the extent and pattern of remote oxidative injuries in lungs by massive ROS production and the following products released from reperfused organs. In the first year, the remote pulmonary injuries from hepatic IR will be focused. We plan to establish an animal model for pulmonary function and pulmonary injury assessments including dynamic compliance (Cdyn), pulmonary edema wet-to-dry ratio (W/D), malondialdehyde (MDA) and histopathological findings under hepatic IR challenge. In the second year, the IR effects during and after CPB on circulating blood cells will be fully studied. We plan to investigate the magnitude, subtypes and timing on ROS production, the changes of oxidative and antioxidant activities of erythrocytes including cytoplasma and cell membrane, the changes on leukocytes and plasma to explore the roles of circulating erythrocytes on oxidative stress in CPB. In the third year, we plan to try propofol, stated having antioxidant in vivo and in vitro, on the remote pulmonary injuries following hepatic IR and CPB.

Visão geral do estudo

Status

Concluído

Intervenção / Tratamento

Descrição detalhada

Seven ml blood sample were taken from arterial line after stabilization of anesthesia (T1), 30 minutes after total CPB (T2), one hour after weaning from CPB (T3) and 24 hours after weaning from CPB (T4). One ml blood sample was immediately wrapped in aluminum foil and kept in ice to immediate measurements of MetHb, COHb and CL (ROS). CL assay was carried out within 2 hours of sampling. Six ml samples remained was placed into tubes containing ethylenediamine tetraacetic acid. Serum were separated ( at 2000rpm for 10 minutes) immediately after sampling and stored at -80℃ for TAS assay, cytokine measurements, malondialdehyde (MDA) determination, complements and leukocyte elastase measurements. Those assay and measurements were carried out within 4 weeks of surgery.

Measurements of hemoglobin (Hb), COHb and MetHb: Hb, COHb and MetHb were measured immediately with ABL520, Radiometer, Copenhagen, Denmark).

Measurement of Redox balance: 0.2ml of fresh drawn blood was used to measure ROS production by lucigenin Chemiluminescence (CL) (detecting superoxide mainly) and luminal CL (detecting H2O2 and HOCl mainly) as previous study.The total antioxidant status in 20 uL of plasma was measured with a total antioxidant status (TAS) kit ( TAS CAL, Randox). Hemodilution effects with CPB, TAS levels at T2 were corrected with the hematocrits. Lipid peroxidation was determined by the thiobarbiturate reaction measuring the formation of MDA in plasma by TBARS assay kit (Cayman chemical co. USA) Cytokines analysis: Inflammatory cytokines were analysis with RayBio human inflammation antibody array 3 according to the manufacturer's instruction. (Cat# AAH-INF-3, RayBiotech Inc. Norcross, GA, USA).29 Measurements of complement activation and leukocytes activation: Complement Component 3a (C3a), C5a, and Human Terminal Complement Complex C5b-9 (C5b-9) were measured with human C3a EIA kit, human C5a EIA kit, Human Terminal Complement Complex C5b-9 kit, Life Science Inc.). Leukocyte elastase were measured by Elisa kit for Human Elastase 2,Neutrophil(NE, Life Science Inc.)

Tipo de estudo

Observacional

Inscrição (Real)

40

Contactos e Locais

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Locais de estudo

      • Taipei, Taiwan, 100
        • National Taiwan University Hospital

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

20 anos a 75 anos (Adulto, Adulto mais velho)

Aceita Voluntários Saudáveis

Não

Gêneros Elegíveis para o Estudo

Tudo

Método de amostragem

Amostra Não Probabilística

População do estudo

patients who receive an open heart surgery under cardiopulmonary bypass

Descrição

Inclusion Criteria:

  • age > 20 y/0, need cardiopulmonary bypass

Exclusion Criteria:

  • severe anemia, hematologic diseases, hormone therapy, previous valvular surgery, blood transfusion in recent 3 months

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

Coortes e Intervenções

Grupo / Coorte
Intervenção / Tratamento
1
sequential changes before and after cardiopulmonary bypass including ROS, antioxidant status, leukocyte elastase, complements, inflammatory cytokines
sequential changes of oxidative injuries before and after cardiopulmonary bypass
Outros nomes:
  • oxidative injuries
  • inflammatory cytokines
  • complements
  • leukocyte elastase

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Investigadores

  • Investigador principal: ya-jung cheng, PhD, Department of anesthesia, national taiwan university hospital

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo

1 de agosto de 2008

Conclusão Primária (Real)

1 de novembro de 2010

Conclusão do estudo (Real)

1 de dezembro de 2010

Datas de inscrição no estudo

Enviado pela primeira vez

31 de agosto de 2008

Enviado pela primeira vez que atendeu aos critérios de CQ

31 de agosto de 2008

Primeira postagem (Estimativa)

3 de setembro de 2008

Atualizações de registro de estudo

Última Atualização Postada (Estimativa)

17 de outubro de 2011

Última atualização enviada que atendeu aos critérios de controle de qualidade

13 de outubro de 2011

Última verificação

1 de junho de 2011

Mais Informações

Termos relacionados a este estudo

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