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 requires iron as a co-factor. Iron chelation has been shown to prevent tissue damage in some models. This experiment was carried out to determine whether iron chelation with deferoxamine (DFO) would prevent lung damage in a swine model of Gram-negative septicemia. Fifteen animals were randomized to control, Pseudomonas aeruginosa infusion at a rate of 2 x 10(7) colony forming units/20 kg/min (septic group), or Pseudomonas infusion combined with DFO pretreatment at a dose of 80 mg/kg/h (septic-treated group). Three of six septic-treated animals became severely hypotensive and died during the course of the experiment as opposed to none of six septic animals. Surviving septic-treated animals were significantly hypotensive (60 +/- 24 mmHg mean arterial pressure) compared to septic (122 +/- 9 mmHg) and control (109 +/- 8 mmHg) animals. DFO did not improve respiratory function (e.g., pO2) or morphology in septic 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.
Mustard
R A
RA
Department of Surgery and Anesthesia, Wellesley Hospital, Toronto, Ontario, Canada.
Bohnen
J M
JM
Mullen
J B
JB
Schouten
B D
BD
Swanson
H T
HT
D000818:Animals; D003676:Deferoxamine / Q000493:pharmacokinetics / Q000494:pharmacology*; D004195:Disease Models, Animal; D016905:Gram-Negative Bacterial Infections / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D006439:Hemodynamics; D007022:Hypotension / Q000139:chemically induced* / Q000150:complications / Q000401:mortality; D008168:Lung / Q000503:physiopathology; D011550:Pseudomonas aeruginosa; D012120:Respiration Disorders / Q000503:physiopathology; D015996:Survival Rate; D013552:Swine
D003676:Deferoxamine