RESUMO
The purpose of this article is to describe mechanisms of cell death in patients with acute myocardial infarction, particularly the activation of the complement system. Various pro-inflammatory cytokines, released by the inflamed tissue, play a role in the activation of the complement system. Several complement inhibitors have been developed to reduce tissue damage following ischemia. According to animal studies the deleterious effects of activators of the complement system can be diminished by complement inhibition. Several clinical studies have been conducted for the potential treatment of cell injury during acute myocardial infarction. C1 inhibitor dose-dependently inhibited complement activation and appeared to reduce myocardial injury after reperfusion therapy in patients with acute myocardial infarction. C1 inhibitor dose-dependently reduced plasma levels of C4 activation fragments. In addition, cardiac enzymes (troponin T and creatine kinase-MB) returned to baseline levels more rapidly among patients treated with C1 inhibitor, compared with controls. Furthermore, preliminary results from a placebo-controlled trial indicate that treatment with intravenous pexelizumab (anti-C5 antibody) was well tolerated in a large number of patients undergoing coronary artery bypass graft surgery. Further, more randomized trials are necessary to clarify the clinical significance of this new and innovative treatment with complement inhibition.
Assuntos
Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Animais , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Morte Celular , Ensaios Clínicos como Assunto , Ativação do Complemento/efeitos dos fármacos , Proteínas Inativadoras do Complemento 1 , Proteína Inibidora do Complemento C1 , Complemento C5/antagonistas & inibidores , Complemento C5/imunologia , Fibrinolíticos/uso terapêutico , Humanos , Infarto do Miocárdio/complicações , Infarto do Miocárdio/terapia , Traumatismo por Reperfusão Miocárdica/etiologia , Traumatismo por Reperfusão Miocárdica/patologia , Serpinas/uso terapêutico , Anticorpos de Cadeia ÚnicaAssuntos
Parada Cardíaca/terapia , Hipotermia Induzida , Distribuição de Qui-Quadrado , Feminino , Escala de Coma de Glasgow , Parada Cardíaca/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Prognóstico , Estatísticas não Paramétricas , Sobreviventes , Fatores de Tempo , Resultado do TratamentoAssuntos
Proteínas Inativadoras do Complemento 1/efeitos adversos , Infarto do Miocárdio/tratamento farmacológico , Animais , Antitrombina III/efeitos dos fármacos , Ativação do Complemento/efeitos dos fármacos , Proteínas Inativadoras do Complemento 1/uso terapêutico , Proteína Inibidora do Complemento C1 , Modelos Animais de Doenças , Cães , Relação Dose-Resposta a Droga , Coração/efeitos dos fármacos , Heparina/farmacologia , Humanos , Isquemia Miocárdica/tratamento farmacológico , Peptídeo Hidrolases/efeitos dos fármacos , Projetos Piloto , Risco , Suínos , Resultado do TratamentoRESUMO
To study the state and diagnostic value of plasma tissue factor (TF) in patients with acute coronary syndromes (ACS), we quantitatively compared plasma TF antigen and TF activity in 90 early-hospitalised patients with chest pain. Using high-affinity antibodies, a sensitive assay for TF antigen was developed with a detection limit of 40 fmol/l. One of the antibodies was used to capture TF from plasma and, after elution and dialysis-free reconstitution in phospholipid-glucoside micelles, absolute amounts of TF activity could be measured with a detection limit of 80 fmol/l. All TF in plasma was found to be exposed, and a value of 2.5(1.1-14.8) pmol/l (median with range) was found for TF antigen. Most of this TF antigen (70-80%) circulated in a (potentially) functional state. Left in its in vivo state, however, TF captured from plasma was totally inactive, probably because of the lack of a procoagulant matrix. Compared with controls with non-cardiac chest pain, TF activity was unchanged and TF antigen about 25% elevated in ACS patients. Combined with the markers prothrombin fragment F1+2 and fatty acid-binding protein, TF did not improve the early diagnosis of ACS.