DEFEROXAMINE INDUCES HYPOTENSION IN EXPERIMENTAL GRAM-NEGATIVE SEPTICEMIA

Multiple organ system failure may result from tissue damage caused by activated neutrophils or endotoxin. A significant part of this tissue damage is due to peroxidation induced by oxygen-free radicals and requ ires iron as a co-factor. Iron chelation has been shown to prevent tis sue damage in some models. This experiment was carried out to determin e whether iron chelation with deferoxamine (DFO) would prevent lung da mage in a swine model of Gram-negative septicemia. Fifteen animals wer e randomized to control, Pseudomonas aeruginosa infusion at a rate of 2 x 10(7) colony forming units/20 kg/min (septic group), or Pseudomona s infusion combined with DFO pretreatment at a dose of 80 mg/kg/h (sep tic-treated group). Three of six septic-treated animals became severel y hypotensive and died during the course of the experiment as opposed to none of six septic animals. Surviving septic-treated animals were s ignificantly hypotensive (60 +/- 24 mmHg mean arterial pressure) compa red to septic (122 +/- 9 mmHg) and control (109 +/- 8 mmHg) animals. D FO did not improve respiratory function (e.g., pO2) or morphology in s eptic animals. We conclude that iron-chelation therapy with DFO at the above dosage results in a significant deterioration in cardiovascular function in septic swine. Lung damage was not prevented.