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    The effects of aprotinin and steroids on generation of cytokines during coronary artery surgery
    (W B Saunders Co-Elsevier Inc, 2001) Türköz, A; Çigli, A; But, K; Sezgin, N; Türköz, R; Gülcan, Ö; Ersoy, MÖ
    Objectives: To compare the efficacy of aprotinin and methylprednisolone in reducing cardiopulmonary bypass (CPB)-induced cytokine release, to evaluate the effect of myocardial cytokine release on systemic cytokine levels, and to determine the influence of cytokine release on perioperative and postoperative hemodynamics. Design: Prospective, randomized clinical trial. Setting: University teaching hospital and clinics. Participants: Thirty patients undergoing elective coronary artery bypass graft surgery. Interventions: Patients were randomly allocated into groups treated with aprotinin (n = 10) or methylprednisolone (n = 10) or into an untreated control group (n = 10). Aprotinin-treated patients received aprotinin as a high-dose regimen (6 x 10(6) KIU), and methylprednisolone-treated patients received methylprednisolone (30 mg/kg intravenously) before CPB. Measurements and Main Results: Patients were analyzed for hemodynamic changes and alveolar-arterial PO2 difference (AaDO(2)) until the first postoperative day. Plasma levels of proinflammatory cytokines (tumor necrosis factor [TNF]a, interleukin [IL]-1 beta, IL-6, and IL-8) were measured in peripheral arterial blood immediately before the induction of anesthesia, 5 minutes before CPB, 3 minutes after the start of CPB, 2 minutes after the release of the aortic cross-clamp, 1 hour after CPB, 6 hours after CPB, and 24 hours after CPB; and in coronary sinus blood immediately before CPB and 2 minutes after the release of the aortic cross-clamp. The hemodynamic parameters did not differ among the groups throughout the study. After CPB, AaDO(2) significantly increased (p < 0.05) in all groups. A significant decrease in AaDO(2) was observed in aprotinin-treated patients at 24 hours after CPB compared with the other groups (p < 0.05). TNF-a level from peripheral arterial blood significantly increased in control patients 1 hour after CPB (p < 0.01) and did not significantly increase in methylprednisolone-treated patients throughout the study. In all groups, IL-6 levels increased after the release of the aortic cross-clamp and reached peak values 6 hours after CPB. At 6 hours after CPB, the increase in IL-6 levels in methyl prednisolone-treated patients was significantly less compared with levels measured in control patients and aprotinin-treated patients (p < 0.001). In control patients, IL-8 levels significantly increased 2 minutes after the release of the aortic cross-clamp (p < 0.05), and peak values were observed 1 hour after CPB (p < 0.01). IL-8 levels in control patients were significantly higher compared with patients treated with aprotinin and patients treated with methylprednisolone 1 hour after CPB (p < 0.05). Conclusion: This study showed that methylprednisolone suppresses TNF-, IL-6, and IL-8 release; however, aprotinin attenuates IL-8 release alone. Methylprednisolone does not produce any additional positive hemodynamic and pulmonary effects. An improved postoperative AaDO(2) was observed with the use of aprotinin. Copyright (C) 2001 by W.B. Saunders Company.