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Portable Low-Volume Therapy for Severe Blood Loss

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Technical Report,09 May 2014,08 May 2015

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University of Minnesota Minneapolis United States

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In this Year 4 report we integrate our major results to date to show the overall advances that we have made in the optimization of a small volume therapy that increases survivability of lethal hemorrhagic shock in rats. This includes our results using a small-volume 1 mlkg resuscitation fluid based on hibernation physiology that has three main components 4 M D-stereoisomer of beta-hydroxybutyrate BHB, 43 mM melatonin, and 20 percent DMSO. Ten-day mean survival showed a dose-dependent trend rats survived longer with higher concentration of infused BHB 4 M BHB, 7.38 plus or minus 1.75 days 2 M BHB, 5.25 plus or minus 2.22 days 0.4 M BHB, 2.07 plus or minus 2.05 days. Administering 4 M BHB without melatonin resulted in low mean survival times 4.38 plus or minus 1.42 days. All treatments containing both 4 M BHB and melatonin, regardless of melatonin concentration, resulted in mean survival times of similar to 7.5 days. Conclusions There is a dose-dependent trend in which higher BHB concentration resulted in higher percent survival over 10 days. Melatonin provides therapeutic effects at very low concentrations evident by survival when administering a solution containing 10exp 6-fold lower melatonin than previously published. Melatonin is essential for survival since 4 M BHB without melatonin had a considerably reduced survival rate.

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  • Medicine and Medical Research

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