Polymyxin-dextran antiendotoxin pretreatment in an ovine model of normotensive sepsis.
OBJECTIVE
To test the hypothesis that adult sheep pretreated with polymyxin-dextran and then made septic by cecal ligation and perforation would have fewer changes in microvascular integrity and cellular architecture in extrapulmonary organs.


METHODS
Prospective, randomized, double-blind, placebo-controlled animal study.


METHODS
An animal research facility in a university-affiliated hospital.


METHODS
Mature, male Suffolk sheep (32 to 67 kg).


METHODS
Animals with chronic indwelling catheters were pretreated with polymyxin B-dextran (6 mg/kg) or placebo (dextran) and an intra-abdominal focus of infection was then produced by cecal ligation and perforation. Treatment (polymyxin B or placebo) was continued every 8 hrs for 48 hrs.


RESULTS
Forty-eight hours after randomization, the polymyxin B-dextran group manifested significantly less pyrexia (p = .04), higher mean arterial pressures (p = .02), less variable serum albumin concentrations (p = .05), and a trend toward decreased lactate concentrations (p = .10). Qualitative morphometry and semiquantitative scoring of tissue from gastrocnemius muscle demonstrated that polymyxin B-dextran-treated sheep had significantly increased total capillary (p = .04) and capillary luminal areas (p = .038) and less mitochondrial swelling and damage (p = .03) compared with the placebo sheep.


CONCLUSIONS
Pretreatment of sheep in a polymicrobial, peritonitis model of sepsis with polymyxin B-dextran resulted in a significant amelioration of sepsis-induced ultrastructural damage. In placebo-treated control animals, these ultrastructural lesions were associated with a greater severity of sepsis, as measured by the presence of pyrexia, increased lactate concentrations, and less stable blood pressures. These findings justify the investigation of the effects of polymyxin B-dextran in a post onset model of sepsis.
Doig
G S
GS
The A. C. Burton Vascular Biology Laboratory, Victoria Hospital Research Institute, and The Program in Critical Care, University of Western Ontario, London, Canada.
Martin
C M
CM
Sibbald
W J
WJ
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D003911:Dextrans / Q000008:administration & dosage; D004731:Endotoxins / Q000037:antagonists & inhibitors*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000473:pathology; D010952:Plasma Substitutes / Q000008:administration & dosage; D011112:Polymyxin B / Q000627:therapeutic use*; D011292:Premedication; D018805:Sepsis / Q000517:prevention & control*; D012756:Sheep
D000900:Anti-Bacterial Agents; D003911:Dextrans; D004731:Endotoxins; D010952:Plasma Substitutes; D011112:Polymyxin B