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Cytokine activation (tumor necrosis factor - a) and clinical response induced by cardiopulmonary bypass

Luiz Antônio Brasil; Walter José Gomes; Reinaldo Salomão; Ênio Buffolo

DOI: 10.1590/S0102-76381996000300009

ABSTRACT

Systemic inflammatory response syndrome induced by cardiopulmonary bypass (CPB) is responsible for organ dysfunctions observed in some patients. The tumor necrosis factor-alpha (TNF-a) has been implicated in many clinical manifestations following cardiac operations with CPB, mainly in the vasoplegic syndrome. The purpose of this study was to verify the TNF-a release and its possible effects in patients with coronary atherosclerosis undergoing coronary artery surgery with and without CPB. Twenty patients were studied, 10 with CPB(Group I) and 10 without CPB(Group II). Serial blood samples were obtained during and until 48 hours after surgery in order to measure circulating TNF-a presence (using enzyme-linked immunosorbent assay-ELISA), leukocyte count and erythrocytes sedimentation rate. Hemodynamic parameters as blood pressure and cardiac rate, body temperature, orotracheal tubing time, postoperative bleeding and inotropic drugs requirements were also compared. Statistical significance was assumed when the p value was less than 0.05. Serum levels of TNF-a (limit detection of the assay = 10 pg/mL) were detected in 6 patients from Group I (60%). This cytokine was detected in Group II. The TNF-a peaked soon after the CPB starting and remained detectable 48 hours postoperatively. The patients of Group I had hypotension in relation to Group II (7.4 ± 1.0 vs 8.5 ± 0.67). They also required more inotropic drugs (8 vs 1), had a higher cardiac rate (114.2 ± 8.0 vs 98 ± 10 bpm), hyperthermia (37.17 ± 0.54 vs 36.67 ± 0.35ºC), more postoperative bleeding (820 ± 120 mL vs 360 ± 84 mL), a longer orotracheal tubing time (13.6 ± 2.2 vs 9.3 ± 1.4 horas) and a more pronounced leucocytosis. We concluded that CPB induces the TNF a release and leads hemodynamic and organic alterations that can be deleterious to patients. It may play a role on the pathophysiology of the alterations observed in this study and the inhibition of the TNFa could contribute to minimize these effects.

RESUMO

A síndrome de resposta inflamatória sistêmica induzida pela circulação extracorpórea (CEC) é responsável pela disfunção de órgãos observada em alguns pacientes. O fator de necrose tumoral alfa (TNFa) tem sido implicado em várias manifestações clínicas no pós-operatório de cirurgia cardíacas com utilização de CEC, principalmente na síndrome vasoplégica. O objetivo deste estudo foi verificar a liberação e os possíveis efeitos do TNFa em pacientes com aterosclerose coronária, submetidos a revascularização do miocárdio, com ou sem CEC. Foram estudados 20 pacientes, sendo 10 com uso de CEC (Grupo I) e 10 sem CEC (Grupo II). Amostras sangüíneas seriadas foram colhidas durante a intervenção e até 48 horas após, sendo analisados a presença de TNFa circulante (método imunoenzimático ELISA), contagem de leocócitos e velocidade de hemosedimentação (VHS). Também foram comparados na evolução pós-operatória dos pacientes os parâmetros hemodinâmicos (pressão arterial e freqüência cardíaca), temperatura, tempo de intubação orotraqueal, sangramento pós-operatório e necessidade de drogas vasoativas. Na análise estatística foram considerados significativos valores de p<0,05. No Grupo I, níveis plasmáticos de TNFa (> 10 pg/ml) foram detectados em 6 (60%) pacientes. No Grupo II não ocorreu detecção da citocina. Os picos de TNFa ocorreram logo após o inicio da CEC e foram detectados até 48 horas após. Houve maior predominância no Grupo I em relação ao Grupo II de hipotensão arterial (7,4 ± 1,0 vs 8,5 ± 0,67), maior necessidade de drogas vasoativas (8 vs 1), freqüência cardíaca mais elevada (114,2 ± 8,0 vs 98 ± 10 bpm), maior hipertemia (37,17 ± 0,54 vs 36,67 ± 0,35ºC), maior sangramento pós-operatório (820 ± 120 ml vs 360 ± 84 mL), tempo de intubação orotraqueal mais prolongado (13,6 ± 2,2 vs 9,3 ± 1,4 horas) e maior leucocitose. Concluímos que a CEC induz a liberação de TNFa e predispõe a alterações hemodinâmicas e orgânicas que podem ser deletérias para os pacientes. É possível que o TNF a esteja envolvido na fisiopatogenia das alterações observadas no presente estudo e a inibição de sua ativação poderia, então, contribuir para minimizar estes efeitos.
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