Cellular Energetics in Hemorrhagic Shock: Restoring Adenosine Triphosphate to the Cells

BACKGROUND: This is a review of studies with two agents, glutamine and crocetin, which have been found to enhance recovery of cellular adenosine triphosphate (ATP) and adenosine diphosphate after hemorrhagic shock. METHODS: The studies used a sublethal (30 minutes) reservoir shock model in 300- to 350-g, male, Sprague-Dawley rats, using either ketamine-xylazine or isoflurane anesthesia. Glutamine was given as a 3% (21 mmol/L) solution in Ringer's lactate (630 mg/kg). Crocetin was given as a 500 nmol/L solution in Ringer's lactate (2 mg/kg). RESULTS: Both glutamine and crocetin caused recovery of ATP to baseline levels (9.0 micromol/g) within 60 to 120 minutes after resuscitation. Xanthine levels returned more rapidly to baseline (0.1 micromol/g). Both agents prevented the elevation in apoptosis seen in controls at 24 and 48 hours. CONCLUSION: Glutamine is a metabolic substrate and a precursor of ATP synthesis. Crocetin enhances oxygen diffusivity in plasma. Both agents restore cellular energy stores to normal after hemorrhagic shock and produce a marked diminution in the extent of apoptosis postshock. Their mechanism of action probably involves prevention of mitochondrial damage.