Effect of antioxidants in experimental Escherichia coli septicemia.
Free radicals have been implicated in the pathogenesis of gram-negative bacterial sepsis. We assessed the effectiveness of antioxidants and chelators to alter oxidative injury in established severe experimental Escherichia coli septicemia. One hour after challenge by intraperitoneal injection of bacteria, 36 rabbits were treated with moxalactam and randomized in sets of three to receive either placebo, superoxide dismutase (SOD), or a combination of antioxidants and chelators consisting of SOD, sodium thiosulfate, alpha-tocopherol, deferoxamine, and diethyldithiocarbamate. Throughout the course of treatment, levels of bacteremia and endotoxemia were similar among the three experimental groups. Neither antioxidant-treated group was significantly different from the control group in mean arterial blood pressure, leukocyte count, platelet count, core temperature, blood lactate, oxygenation or survival. Arterial pH and [HCO3-] were significantly lower in the antioxidant combination group compared to the control and SOD groups (P less than .01). In this model, antioxidant and chelator therapy does not substantially ameliorate established septicemia.
Broner
C W
CW
Laboratories of St. Jude Children's Research Hospital, Memphis, Tennessee.
Shenep
J L
JL
Stidham
G L
GL
Stokes
D C
DC
Fairclough
D
D
Schonbaum
G R
GR
Rehg
J E
JE
Hildner
W K
WK
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004357:Drug Synergism; D004731:Endotoxins / Q000097:blood; D004927:Escherichia coli Infections / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D009070:Moxalactam / Q000627:therapeutic use; D011817:Rabbits; D018805:Sepsis / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D012772:Shock, Septic / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000494:pharmacology* / Q000627:therapeutic use
D000975:Antioxidants; D002614:Chelating Agents; D004731:Endotoxins; D013482:Superoxide Dismutase; D009070:Moxalactam