D-β-Hydroxybutyrate and melatonin for treatment of porcine hemorrhagic shock and injury: A melatonin dose-ranging study

Andrea Wolf, Kristine E. Mulier, Sydne L. Muratore, Gregory J. Beilman

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Abstract

Objective: Treatment with a combination of d-β-hydroxybutyrate (BHB) and melatonin (M) improves survival in hemorrhagic shock models. Our objective was to find the most effective melatonin concentration in combination with 4 molar BHB (4 M BHB). Survival and markers of organ injury were analyzed in pigs exposed to pulmonary contusion, liver crush injury, and hemorrhagic shock and treated with lactated Ringer's solution; 4 M BHB/43 mM M; 4 M BHB/20 mM M; 4 M BHB/10 mM M; 4 M BHB/4.3 mM M; or 4 M BHB/0.43 mM M. This work is an extension of a previously published research study. Results: Survival was highest in pigs receiving 4 M BHB/43 mM M (13/14), followed by lactated Ringer's solution (11/16) and BHB/M with decreased melatonin concentrations (4 M BHB/20 mM M 3/6, 4 M BHB/10 mM M 2/6, 4 M BHB/4.3 mM M 3/6, 4 M BHB/0.43 mM M 1/6, p = 0.011). High mortality was associated with increases in serum lactate, higher liver and muscle injury markers and decreases in PaO2:FiO2 ratios. Our study indicates that treatment with 4 M BHB and melatonin concentrations below 43 mM lack the survival benefit observed from 4 M BHB/43 mM melatonin in pigs experiencing hemorrhagic shock and polytrauma.

Original languageEnglish (US)
Article number649
JournalBMC Research Notes
Volume10
Issue number1
DOIs
StatePublished - Nov 29 2017

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Keywords

  • Antioxidant
  • Blood loss
  • Hibernation
  • Ketone bodies
  • Melatonin
  • Resuscitation

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