Glycine improves survival after hemorrhagic shock in the rat.
This study investigated the effect of glycine on hemorrhagic shock in the rat. Rats were bled to maintain mean arterial pressure at 30-35 mm Hg for 1 h and subsequently resuscitated with 60% shed blood and lactated Ringer's solution. Only 20% of rats receiving saline just prior to resuscitation survived 72 h after shock. Survival was increased by glycine (11.2-90.0 mg/kg, i.v.) in a dose-dependent manner (half-maximal effect = 25 mg/kg) and reached maximal values of 78% at 45 mg/kg. Eighteen hours after resuscitation, creatinine phosphokinase increased 23-fold, transaminases increased 33-fold, and creatinine was elevated 2.4-fold, indicating injury to the heart, liver, and kidney, respectively. Pulmonary edema, leukocyte infiltration, and hemorrhage were also observed. In the kidney, proximal tubular necrosis, leukocyte infiltration, and severe hemorrhage in the outer medullary area occurred in rats receiving saline. Glycine reduced these pathological alterations significantly. It has been reported that oxidative stress and tumor necrosis factor(TNF)-alpha-production are involved in the pathophysiology of multiple-organ injury after shock. In this study, free radical production was increased 4-fold during shock, an effect blocked largely by glycine. Increases in intracellular calcium and production of TNF-alpha by isolated Kupffer cells stimulated by endotoxin were elevated significantly by hemorrhagic shock, alterations which were totally prevented by glycine. Taken together, it is concluded that glycine reduces organ injury and mortality caused by hemorrhagic shock by preventing free radical production and TNF-alpha formation.
Zhong
Z
Z
Department of Pharmacology, University of North Carolina, Chapel Hill 27599-7365, USA.
Enomoto
N
N
Connor
H D
HD
Moss
N
N
Mason
R P
RP
Thurman
R G
RG
D000818:Animals; D003401:Creatine / Q000378:metabolism; D003402:Creatine Kinase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005998:Glycine / Q000008:administration & dosage*; D007275:Injections, Intravenous; D007728:Kupffer Cells / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016019:Survival Analysis; D000637:Transaminases / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D014409:Tumor Necrosis Factor-alpha; D000637:Transaminases; D003402:Creatine Kinase; D003401:Creatine; D005998:Glycine