Iron chelation by deferoxamine inhibits lipid peroxidation during cardiopulmonary bypass in humans

Academic Article

Abstract

  • Iron catalysis is involved in oxygen-derived free radical generation and subsequent lipid peroxidation, which have been reported to occur during cardiopulmonary bypass in humans. We assessed the effects of the iron chelator deferoxamine on the susceptibility of circulating low density lipoproteins (LDLs) to induced peroxidation in 20 adult patients (10 controls and 10 treated) undergoing cardiopulmonary bypass for coronary or valve procedures. Deferoxamine was given both intravenously (30 mg/kg body wt, starting 30 minutes before bypass and extending for the next 4 hours) and as an additive to cardioplegic solution (250 mg/l). Blood samples were taken from both atria before and immediately after the end of cardiopulmonary bypass. Plasma lipid peroxidation was assessed by measuring spectrophotometrically the thiobarbituric acid reactive substances (TBARS) content of selectively isolated LDLs after their exposure to a peroxidizing agent. Before cardiopulmonary bypass, the right and left atrial blood values of LDL-TBARS were not significantly different between the two groups. Cardiopulmonary bypass resulted in a lipid peroxidation of significantly greater magnitude in control than in treated patients. Postbypass right atrial values for LDL-TBARS (expressed in μmol/mmol LDL-phospholipids) were 45.7 ± 17.2 (mean ± SEM) in control patients and 6.9 ± 2.9 in treated patients (p < 0.02), whereas in the left atrial blood, LDL-TBARS yielded values of 62.7 ± 20.5 and 10.3 ± 3.9, respectively (p < 0.01). Lipid peroxidation across the lungs, as reflected by ΔLDL-TBARS (left atrial-right atrial blood concentrations) was also significantly greater after bypass in control than in patients treated with deferoxamine (16.9 ± 4.4 vs. 3.3 ± 4.1, p < 0.05). The decreased susceptibility of LDL to lipid peroxidation in treated patients is likely to reflect a greater availability of LDL-bound vitamin E. This in turn suggests a smaller degree of consumption of endogenous antioxidants, particularly in lung tissue, due to a deferoxamine-induced reduction of iron-mediated free radical damage. These data support the concept that deferoxamine could be clinically useful for limiting the component of postbypass organ injury, which is caused by iron-dependent abnormalities of oxidative metabolism.
  • Published In

  • Circulation  Journal
  • Author List

  • Menasche P; Antebi H; Alcindor LG; Teiger E; Perez G; Giudicelli Y; Nordmann R; Piwnica A
  • Volume

  • 82
  • Issue

  • 5 SUPPL.