Abstract
Myocardial ischaemia is one of the major causes of low output syndrome during open heart surgery. Injury associated with ischaemia and reperfusion has been considered to result, in part, from the action of neutrophils, the interaction of neutrophils with vascular endothelial cells, and the effects of cytokines which are mediators that induce and modify reactions between these substances. We investigated cell injury in relation to the concentrations of interleukins 6 and 8 (IL-6 and IL-8), which have recently received attention as neutrophil activators. Neutrophil counts, granulocyte elastase (GEL), IL-6, IL-8, tumour necrosis factor-α (TNF-α), CK, and CK-MB concentrations were determined serially in 11 patients undergoing open heart surgery with cardiopulmonary bypass (CPB). Neutrophil counts (mean ±SD 2717 ±2421 μl−1 preoperatively) peaked 60 min after declamping the aorta at 7432 ±4357 μl−1 (P < 0.01) and remained elevated 7136 ±5194 μl−1 at 180 min (P < 0.01). Plasma GEL level (168 ±71 μg sd L−1 preoperatively) peaked at 1134 ±453 μg · L−1 120 min after declamping of the aorta (P < 0.01) and remained elevated, 1062 ±467 μg · L−1, after 180 min (P < 0.01). Serum IL-6 level (118 ±59 pg · ml−1 preoperatively) peaked at 436 ±143 pg · ml−1 60 min after declamping of the aorta (P < 0.01) and remained elevated, 332 ±109 pg · ml−1, after 180 min. Serum IL-8 level (37 ±44 pg · ml−1 preoperatively) peaked at 169 ±86 pg · ml−1 at 60 min after declamping of the aorta (P < 0.001) and remained elevated at 113 ±78 pg · ml−1 180 min after declamping of the aorta. Serum TNF-α was decreased at 60 min after aortic occlusion but otherwise did not change. Plasma GEL concentrations correlated with serum IL-8 levels (R = 0.7, P = 0.001) and the IL-6 and IL-8 concentrations correlated with the duration of aortic clamping (R = 0.64, P = 0.01, R = 0.7, P = 0.01). We conclude that the increases of IL-6 and IL-8 occur as a result of ischaemia, and suggest that these cytokines participate in reperfusion injury by activating neutrophils.
Résumé
L’ischémie myocardique est une des principales causes du syndrome de bas débit pendant la chirurgie à coeur ouvert. On pense que la lésion associée à l’ischémie et la reperfusion résulte en partie de l’action des neutrophiles, l’interaction des neutrophiles avec les cellules vasculaires endothéliales et l’activité de médiateurs, les cytokines qui induisent et modifient les réactions entre ces substances. Nous avons examiné la relation de la lésion cellulaire avec la concentration des interleukines 6 et 8 (IL-6 et IL-8), qui ont récemment attiré l’attention comme activateurs de neutrophiles. Chez 11 patients soumis à une chirurgie cardiaque ouverte avec circulation extracorporelle (CEC), on mesure en série le décompte des neutrophiles, l’élastase granulocytaire (GEL), l’IL-6 et l’IL-8, le facteur-α. de nécrose tumorale (TNF-α) et la concentration des CK et CK-MB. Le décompte des neutrophiles (moyenne ±SD: 2717 ±2421 μl−1 en préopératoire) atteint un maximum de 7432 ±435 μl−1 60 min après le déclampage de l’aorte (P < 0,01) et demeure élevé, 7136 ±5194 μl−1, à 180 min (P < 0,01). Le niveau de la GEL plasmatique (168 ±71 μg · L−1 en préopératoire) atteint un maximum de 1134 ±453 μg · L−1 après 120 min du déclampage de l’aorte (P < 0,01) et demeure élevé, 1062 ±467 μg · L−1 après 180 min de déclampage (P < 0,01). L’IL-6 sérique (118 ±59 pg · ml−1) atteint un maximum de 436 ±143 pg · ml−1 60 minutes après le déclampage de l’aorte (P < 0,01) et demeure élevé, 332 ±109 pg · ml−1 après 180 min. Le niveau sérique d’IL-8 (37 ±44 pg · ml−1 en préopératoire) atteint un maximum de 169 ±86 pg · ml−1 60 min après le déclampage de l’aorte (P < 0,01) et demeure élevé, 113 ±78 pg · ml−1 après 180 min. Le TNF-α décroît 60 min après le clampage aortique mais ne change plus par la suite. La concentration plasmatique de GEL est en corrélation avec le niveau sérique de l’IL-8 (R = 0,7, P = 0,001). Les concentrations d’IL-6 et d’IL-8 sont en corrélation avec la durée du clampage (R = 0,64, P = 0,01, R = 0,07, P = 0,01). Nous concluons que les augmentations d’IL-6 et d’IL-8 résultent de l’ischémie et nous suggérons qu’en activant les neutrophiles, ces cytokines participent à la genèse de la lésion de reperfusion.
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Kawamura, T., Wakusawa, R., Okada, K. et al. Elevation of cytokines during open heart surgery with cardiopulmonary bypass: participation of interleukin 8 and 6 in reperfusion injury. Can J Anaesth 40, 1016–1021 (1993). https://doi.org/10.1007/BF03009470
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DOI: https://doi.org/10.1007/BF03009470