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Portable Low-Volume Therapy for Severe Blood Loss

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Annual rept. 9 May 2012-8 May 2013

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In Year 1 we examined the low concentration end of the full factorial design for our hibernation-based therapy for hemorrhagic shock Specific Aim 1. We determined that high concentrations of the D-stereoisomer of beta-hydroxybutyrate D-BHB are required to improve survival. We also found that the other key component, melatonin, showed therapeutic benefits at concentrations that were 10-fold lower than previously published Klein et al. 2010. In Year 2 we designed a dose-ranging study to determine if melatonin concentrations could be lowered further and still provide favorable outcomes. Survival curves were compared at 10 days following shock 60 blood loss for 1 hour. Treatments including both BHB and melatonin, even at melatonin concentrations 10-6 lower than previously published, were not statistically different p 0.05 from sham-operated animals with no blood loss. Shocked animals that received BHB only, or NaCl with melatonin, survived for statistically shorter times p 0.05 than shams. Consistent with Specific Aim 2, we also conducted a semi-log dose range from 0 to 50 mgkg of 3-iodothyronamine in normotensive animals to corroborate that this thyroid hormone derivative possessed hypothermia-inducing properties. Temperature curves did not differ between treatments p 0.05. It is possible that hypothermic effects, if any, are masked by anesthesia. Experiments described in Specific Aim 3 have started, but this work is too preliminary to report in this document.

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  • Medicine and Medical Research

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