title: The effects of aprotinin and steroids on generation of cytokines during coronary artery surgery.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Prospective, randomized clinical trial.
  
  
  METHODS
  University teaching hospital and clinics.
  
  
  METHODS
  Thirty patients undergoing elective coronary artery bypass graft surgery.
  
  
  METHODS
  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.
  
  
  RESULTS
  Patients were analyzed for hemodynamic changes and alveolar-arterial PO2 difference (AaDO2) until the first postoperative day. Plasma levels of proinflammatory cytokines (tumor necrosis factor [TNF]-alpha, interleukin [IL]-1beta, 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, AaDO2 significantly increased (p < 0.05) in all groups. A significant decrease in AaDO2 was observed in aprotinin-treated patients at 24 hours after CPB compared with the other groups (p < 0.05). TNF-alpha 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 methylprednisolone-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).
  
  
  CONCLUSIONS
  This study showed that methylprednisolone suppresses TNF-alpha, 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 AaDO2 was observed with the use of aprotinin.
authors.affiliation: Department of Anesthesiology, Inönü University Hospital, Malatya, Turkey. rturkoz@yahoo.com
authors.forename: A
authors.initials: A
authors.lastname: Türköz
authors.forename: A
authors.initials: A
authors.lastname: Ciğli
authors.forename: K
authors.initials: K
authors.lastname: But
authors.forename: N
authors.initials: N
authors.lastname: Sezgin
authors.forename: R
authors.initials: R
authors.lastname: Türköz
authors.forename: O
authors.initials: O
authors.lastname: Gülcan
authors.forename: M O
authors.initials: MO
authors.lastname: Ersoy
mesh_terms: D000368:Aged; D007611:Aprotinin / Q000494:pharmacology*; D001026:Coronary Artery Bypass; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology*; D008875:Middle Aged; D010100:Oxygen / Q000097:blood; D011446:Prospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D007611:Aprotinin; D010100:Oxygen; D008775:Methylprednisolone