title: Administration of glutamine after hemorrhagic shock restores cellular energy, reduces cell apoptosis and damage, and increases survival.
abstract: BACKGROUND
  Hemorrhagic shock causes a rapid depletion of adenosine triphosphate (ATP) and an increase of the terminal metabolite xanthine. Free radicals generated from xanthine oxidase play a major role in cell injury. Programmed cell death, apoptosis, is a major pathway causing reperfusion injury. During apoptosis, cytosolic cytochrome-c is released from damaged mitochondria, and it further initiates activation of apoptosis as evidenced by the appearance of caspase-3. The bcl-2 protein serves as an antiapoptosis found on the mitochondrial membrane. Glutamine has been known as a conditionally essential nutrient and seems to have beneficial effects in critically ill patients. The hypothesis of the present study is that glutamine administered during resuscitation following hemorrhagic shock would restore the depletion of hepatic ATP, reduce cellular apoptosis, and increase survival.
  
  
  METHODS
  Male Sprague-Dawley rats were randomly assigned to 3 groups for resuscitation after the same pattern of hemorrhagic shock: Ringer's lactate (LR 21 ml/kg); Alanine-glycine (LR with alanine 0.15 gm/kg and glycine 0.18 gm/kg); and glutamine (LR with glutamine 0.3 gm/kg). Hepatic ATP and xanthine was measured at different time periods. Hepatic apoptosis was measured and the levels of cytosolic cytochrome-c, caspase-3 and bcl-2 were analyzed. Another group of rats were used for survival study.
  
  
  RESULTS
  Glutamine administered during resuscitation following hemorrhagic shock partially restored the depletion of hepatic ATP, reduced cellular apoptosis, and increased survival.
  
  
  CONCLUSIONS
  Glutamine administration during resuscitation significantly protected the liver from tissue damage caused by hemorrhagic shock. Glutamine supplementation may offer opportunities for therapeutic intervention during and after shock.
authors.affiliation: Departments of Surgery, School of Medicine, UMKC, Kansas City, Missouri 64108, USA.
authors.forename: Rongjie
authors.initials: R
authors.lastname: Yang
authors.forename: Lisa
authors.initials: L
authors.lastname: Martin-Hawver
authors.forename: Charles
authors.initials: C
authors.lastname: Woodall
authors.forename: Ann
authors.initials: A
authors.lastname: Thomas
authors.forename: Nilofer
authors.initials: N
authors.lastname: Qureshi
authors.forename: David
authors.initials: D
authors.lastname: Morrison
authors.forename: Charles
authors.initials: C
authors.lastname: Van Way
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival; D002851:Chromatography, High Pressure Liquid; D045304:Cytochromes c / Q000378:metabolism; D005609:Free Radicals; D005973:Glutamine / Q000008:administration & dosage*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000378:metabolism* / Q000628:therapy*; D019820:Xanthine / Q000378:metabolism
chemical_list: D005609:Free Radicals; D005973:Glutamine; D019820:Xanthine; D000255:Adenosine Triphosphate; D045304:Cytochromes c; D053148:Caspase 3