Hibernation-based blood loss therapy increases survivability of lethal hemorrhagic shock in rats

A small-volume (1 ml/kg) resuscitation fluid based on metabolic adaptations in hibernating mammals was optimized using a rat model of hemorrhagic shock. A previous study of this therapy tested only one concentration of three specific components: 4 M D-stereoisomer of beta-hydroxybutyrate (BHB), 43 m...

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Published in:	Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology Vol. 187; no. 5-6; pp. 769 - 778
Main Authors:	Perez de Lara Rodriguez, Cecilia E., Drewes, Lester R., Andrews, Matthew T.
Format:	Journal Article
Language:	English
Published:	Berlin/Heidelberg Springer Berlin Heidelberg 01-07-2017 Springer Nature B.V
Subjects:	3-Hydroxybutyric Acid - therapeutic use Adaptation Animal Physiology Animals Arousal Biochemistry Biomedical and Life Sciences Biomedicine Blood Dimethyl Sulfoxide - therapeutic use Extreme values Fluid Therapy Hemorrhage Hibernation Human Physiology Ischemia Life Sciences Male Mammals Melatonin Melatonin - therapeutic use Original Paper Rats Rats, Sprague-Dawley Reperfusion Resuscitation Rodents Shock, Hemorrhagic - therapy Survivability Survival Therapy Torpor Zoology Melatonin Fluid resuscitation Hemorrhage Ketone Hibernation Beta-hydroxybutyrate
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Summary:	A small-volume (1 ml/kg) resuscitation fluid based on metabolic adaptations in hibernating mammals was optimized using a rat model of hemorrhagic shock. A previous study of this therapy tested only one concentration of three specific components: 4 M D-stereoisomer of beta-hydroxybutyrate (BHB), 43 mM melatonin, and 20% DMSO. In this study, we considered the range of concentrations of BHB and melatonin seen during the physiological extremes of rapid arousal from hypothermic torpor in natural hibernators and applied these to the non-hibernating Sprague–Dawley rat model. These extremes normally result in ischemia and reperfusion injury in non-hibernating mammals. Dose-ranging studies were conducted for BHB and melatonin in rats with 60% blood loss. BHB was administered at either 4, 2, or 0.4 M concentration in conjunction with 4.3 mM melatonin and 10% DMSO. Subsequently, melatonin was administered at either 4.3, 0.43, 0.0043, 0.000043, or 0 mM in conjunction with 4 M BHB and 2% DMSO. 10-day mean survival showed a dose-dependent trend: rats survived longer with higher concentration of infused BHB (4 M BHB, 7.38 ± 1.75 days; 2 M BHB, 5.25 ± 2.22 days; 0.4 M BHB, 2.07 ± 2.05 days). Administering 4 M BHB without melatonin resulted in low mean survival times (4.38 ± 1.42 days). All treatments containing both 4 M BHB and melatonin, regardless of melatonin concentration, resulted in mean survival times of ~7.5 days. We conclude there is a dose-dependent trend in which higher BHB concentration resulted in improved survival over 10 days.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0174-1578 1432-136X
DOI:	10.1007/s00360-017-1076-7