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Use of Animal Model of Sepsis to Evaluate Novel Herbal Therapies
Published on: April 11, 2012
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Extremely low doses of tissue factor pathway inhibitor decrease mortality in a rabbit model of septic shock.
1Department of Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
Intensive Care Medicine
|August 21, 2001
Summary
Low doses of recombinant human tissue factor pathway inhibitor (TFPI) significantly prolonged survival in a rabbit model of sepsis. These findings suggest lower TFPI doses may be effective in human sepsis trials.
Area of Science:
- Pharmacology
- Critical Care Medicine
- Infectious Diseases
Background:
- Sepsis remains a leading cause of mortality worldwide.
- Effective adjuvant therapies for sepsis are urgently needed.
- Recombinant human tissue factor pathway inhibitor (TFPI) is a potential therapeutic agent.
Purpose of the Study:
- To determine the minimum effective dose of recombinant human TFPI for treating septic shock.
- To evaluate TFPI's efficacy in a rabbit model of Gram-negative bacterial sepsis.
Main Methods:
- Sepsis was induced in New Zealand white rabbits using Escherichia coli.
- Animals received gentamicin and were treated with varying doses of TFPI or vehicle.
- Survival time was the primary outcome measure and analyzed using the Wilcoxen log rank test.
Main Results:
- The highest TFPI dose (50 µg/kg bolus, 0.5 µg/kg/min infusion) resulted in an average survival time of 118 h compared to 81 h in controls.
- A significantly lower dose (100 ng/kg bolus, 1.0 ng/kg/min infusion) also prolonged survival to 119 h versus 57 h in controls.
- Even lower doses showed marginal or no significant survival benefit.
Conclusions:
- Delayed administration of low-dose recombinant human TFPI effectively prolongs survival in antibiotic-treated Gram-negative bacterial sepsis in rabbits.
- These results suggest that lower TFPI doses than previously considered may be viable for human sepsis trials.
- Further research into optimized TFPI dosing for sepsis is warranted.
