Evaluation of surrogate markers of impending death in the galactosamine-sensitized murine model of bacterial endotoxemia.
OBJECTIVE
When evaluating vaccines for efficacy against gram-negative endotoxemia, the challenge has historically required death of a large percentage of test subjects. We attempted to identify surrogate markers of impending death to allow for early euthanasia without interfering with experimental data collection.


METHODS
Galactosamine-sensitized mice (n = 140) were inoculated intraperitoneally with various dosages of endotoxin, and development of clinical signs of disease--body temperature, body weight, hunched posture, ruffled coat, inability to ambulate, and loss of consciousness--was evaluated.


RESULTS
Wide fluctuations in body temperature (+/- 4 degrees C) were observed in survivors and nonsurvivors. Posture, coat, and body weight were not accurate predictors of death. Only inability to ambulate, with a positive predictive value of 100% (11 of 11), accurately predicted death in the experimental mice of this study.


CONCLUSIONS
Using this surrogate marker, loss of ability to ambulate, 11 of 13 mice that developed this sign could have been euthanized early, preventing anywhere from 2 to 22 h of potential distress prior to death.
Krarup
A
A
Walter Reed Army Institute of Research Division of Veterinary Medicine, Washington, DC, USA.
Chattopadhyay
P
P
Bhattacharjee
A K
AK
Burge
J R
JR
Ruble
G R
GR
D000818:Animals; D015415:Biomarkers; D001831:Body Temperature; D001835:Body Weight; D003643:Death; D019446:Endotoxemia / Q000401:mortality*; D004731:Endotoxins / Q000008:administration & dosage*; D004926:Escherichia coli; D005260:Female; D005688:Galactosamine / Q000008:administration & dosage*; D006197:Hair; D007711:Klebsiella pneumoniae; D008124:Locomotion; D051379:Mice; D008807:Mice, Inbred BALB C; D011187:Posture; D011550:Pseudomonas aeruginosa; D014474:Unconsciousness
D015415:Biomarkers; D004731:Endotoxins; D005688:Galactosamine