Effect of meningococcal endotoxin in a rabbit model of shock.
Endotoxin in the form of a lipooligosaccharide (LOS) plays a key role in the development of shock in meningococcal sepsis. To examine hemodynamic and biochemical alterations during meningococcal endotoxic shock, we established a rabbit model. Thirty-nine rabbits, weighing 2.5-4.4 kg, were studied. After anesthesia with intramuscular ketamine (20 mg/kg) and xylazine (4 mg/kg), femoral venous and arterial catheters were inserted. Control animals received only saline, while rabbits in each of four additional groups were given LOS in 10-fold increments from 0.1 microgram/kg to 100 microgram/kg. Mean arterial pressure (MAP), heart rate (HR), respirations (RR), temperature (T), urine output, and arterial blood gases (pH, PCO2, PO2, and bicarbonate) were determined at baseline and hourly. Endotoxin levels and TNF levels were measured at 30, 60, 120, 180, 240, 300, and 360 min post-LOS. Survival was recorded. One-way analysis of variance (ANOVA) and the Scheffe procedure, paired samples t-test, two-tailed t-test, and Fisher's exact test were used. Pearson's coefficients were calculated. Animals receiving meningococcal LOS developed tachycardia and compensated metabolic acidosis with an initially normal pH and MAP. With progression of the shock state, the pH decreased and hypotension ensued. Maximal levels of endotoxin were measured 30 min after LOS injection and declined during the ensuing 6 hr. TNF rose from undetectable to markedly elevated levels and peaked at 60-120 min post-LOS. Increasing the amount of injected endotoxin produced more profound degrees of shock until a dose of 10.0 micrograms/kg was reached. There was no correlation between serum TNF at 60 min and survival at 6 hr or 24 hr.(ABSTRACT TRUNCATED AT 250 WORDS)
Caputo
G L
GL
Division of Emergency Medicine, Children's Hospital, Boston, Massachusetts 02115.
Baldwin
G
G
Alpert
G
G
Parsonnet
J
J
Gillis
Z A
ZA
Siber
G
G
Fleisher
G
G
D000818:Animals; D001774:Blood Chemical Analysis; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D004195:Disease Models, Animal; D004731:Endotoxins / Q000633:toxicity*; D006339:Heart Rate / Q000187:drug effects; D008589:Meningococcal Infections / Q000097:blood* / Q000139:chemically induced / Q000652:urine; D009345:Neisseria meningitidis; D011817:Rabbits; D012119:Respiration / Q000187:drug effects; D012772:Shock, Septic / Q000097:blood* / Q000139:chemically induced / Q000652:urine; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha