ELEVATION OF CYTOKINES DURING OPEN-HEART-SURGERY WITH CARDIOPULMONARY BYPASS - PARTICIPATION OF INTERLEUKIN-8 AND INTERLEUKIN-6 IN REPERFUSION INJURY

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-alpha (TNF-alpha), 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 mul-1 preoperatively) peaked 60 min after declamping the aorta at 7432 +/- 4357 mul-1 (P < 0.01) and remained elevated 7136 +/- 5194 mul-1 at 180 min (P < 0.01). Plasma GEL level (168 +/- 71 mug . L-1 preoperatively) peaked at 1134 +/- 453 mug - L- 1 120 min after declamping of the aorta (P < 0.01) and remained elevated, 1062 +/- 467 mug . 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-alpha 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.