Deferoxamine reduces neutrophil-mediated free radical production during cardiopulmonary bypass in man

Academic Article

Abstract

  • We assessed the effects of the iron chelator deferoxamine in 24 adult patients (12 controls, 12 treated) undergoing cardiopulmonary bypass for various cardiac operations. Deferoxamine was given both intravenously (30 mg/kg of body weight, starting 30 minutes before and ending 30 minutes after bypass) and as an additive to the cardioplegic solution (250 mg/L). Right atrial blood samples were taken before, during, and after bypass, and isolated polymorphonuclear neutrophils were evaluated for their capacity to generate superoxide radicals after stimulation with N-formyl-methionyl-leucyl-phenylalanine (FLMP, 10-7mol) and phorbol myristate acetate (100 ng/ml). At the same sampling times, measurement of the plasma levels of 6-keto-prostaglandin F(1α), the stable derivative of prostacyclin, was used as an index of membrane phospholipid breakdown. The two groups were not significantly different with regard to age, duration of bypass, and quantitative changes in polymorphonuclear neutrophil counts during the operation. Before bypass, the superoxide production of FMLP-stimulated polymorphonuclear neutrophils was comparable in the two groups. Conversely, after bypass, polymorphonuclear neutrophils harvested from deferoxamine-treated patients produced significantly fewer superoxide radicals than those of control patients (1.9 ± 0.3 versus 3.7 ± 0.2 nmol/106 polymorphonuclear neutrophils per minute, p < 0.05). Stimulation of polymorphonuclear neutrophils by phorbol myristate acetate yielded similar changes, as the postbypass superoxide production was 12.6 ± 2.5 nmol/106/min in control patients and 7.1 ± 0.9 nmol/106/min in those receiving deferoxamine (p < 0.05). In contrast, plasma levels of 6-keto-prostaglandin F(1α) were not significantly different between the two groups. We conclude that deferoxamine-exposed polymorphonuclear neutrophils have a decreased oxidative responsiveness, compatible with the fact that they may have been less 'primed' by secretagogues released during bypass, as compared with cells of untreated patients. Our results are consistent with the hypothesis that deferoxamine, by inhibiting iron-catalyzed free radical production, may limit the free radical-mediated amplification of the inflammatory response to bypass and as such could be effective in reducing the harmful effects of extracorporeal circulation.
  • Digital Object Identifier (doi)

    Author List

  • Menasche P; Pasquier C; Bellucci S; Lorente P; Jaillon P; Piwnica A
  • Start Page

  • 582
  • End Page

  • 589
  • Volume

  • 96
  • Issue

  • 4