Portable Low-Volume Therapy for Severe Blood Loss

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 mg/kg 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. The original document contains color images.