Small-volume D-β-hydroxybutyrate solution infusion increases survivability of lethal hemorrhagic shock in rats

Amanda H Klein, Scott M. Wendroth, Lester R Drewes, Matthew T. Andrews

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

A small-volume therapeutic approach based on the biochemistry of hibernating mammals was evaluated to test the hypothesis that passive hypothermia and systemic administration of D-β-hydroxybutyrate (D-BHB) plus melatonin will increase survival of animals subjected to hemorrhagic shock ([HS] 60% blood loss). Anesthetized Sprague-Dawley male rats (320 ± 23 g) underwent controlled loss of 60% blood volume. Rats were instrumented to measure mean arterial pressure, body temperature (Tb), and heart rate. A passive decrease in rat Tb in response to HS significantly increased survival over animals maintained at 37°C (n = 5-6). Infusion of 4 M D-BHB, at a volume of only 5.5% of the total blood removed, significantly prolonged survival to a mean of 3 h compared with 90 min using equal osmolar 4 M NaCl (n = 6). In experiments where the shed blood was returned after 1 h of 60% blood loss, 4% fluid replacement with 4 M D-BHB plus 43 mM melatonin significantly prolonged survival up to 10 days after blood return compared with 4 M NaCl plus 43 mM melatonin and other control solutions (n = 10). We conclude that a slow decrease in animal Tb resulting from 60% blood loss, combined with infusion of 4 M D-BHB plus 43 mM melatonin, was beneficial for long-term survival after return of shed blood. This HS therapy is designed as a portable low-volume solution for further evaluation in a large-animal model and is ultimately intended for use in HS patients by first responders.

Original languageEnglish (US)
Pages (from-to)565-572
Number of pages8
JournalShock
Volume34
Issue number6
DOIs
StatePublished - Dec 1 2010

Keywords

  • Hibernation
  • fluid resuscitation
  • hemorrhage
  • hypothermia
  • ketone
  • melatonin

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