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

• Published in: Shock (Augusta, Ga.) Ga.), 2010-12, Vol.34 (6), p.565-572
• Main Authors: Klein, Amanda H, Wendroth, Scott M, Drewes, Lester R, Andrews, Matthew T
• Format: Article
• Language: English
• Subjects: 3-Hydroxybutyric Acid - administration & dosage; 3-Hydroxybutyric Acid - blood; Animals; Fluid Therapy - methods; Male; Melatonin - administration & dosage; Melatonin - therapeutic use; Rats; Rats, Sprague-Dawley; Shock, Hemorrhagic - blood; Shock, Hemorrhagic - drug therapy
• ISSN: 1073-2322; 1540-0514
• DOI: 10.1097/SHK.0b013e3181e15063

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.