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Open Access Evaluation of Surrogate Markers of Impending Death in the Galactosamine-Sensitized Murine Model of Bacterial Endotoxemia

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Abstract:

Background and Purpose: 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°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.

Conclusion: 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.

Document Type: Research Article

Publication date: October 1, 1999

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  • Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.

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