The effect of valproic acid in alleviating early death in burn shock.
The aim of this study was to examine whether administration of valproic acid (VPA) improves blood circulation and survival after lethal burn shock. Forty adult male Beagle dogs underwent a 50% TBSA full-thickness flame injury. In the first 24 h after burn, animals were randomly divided into four groups: NR group received no treatment. VPA group and 2M2P(2-methyl-2-pentenoic acid) group received either VPA or 2M2P (100 mg of the either drug in 20 mL of normal saline) intravenously. VR group received intravenous infusion of lactated Ringer's solution according to Parkland formula. In the second 24 h after burn the animals of all groups received delayed IV fluid resuscitation. Hemodynamic variables and biochemical parameters were determined with animals in the conscious and cooperative state. From 4 h after burn on, the levels of mean arterial pressure, cardiac index, plasma volume and intestinal mucosal blood perfusion in VPA group were significantly higher, and the levels of parameters of organ function and serum tumor necrosis factor-α were lower than those in NR group and 2M2P group (all P<0.05). Survival at 72 h after burn was in following order: VR (100%)>VPA (60%)>2M2P (30%)>NR (10%). Our results showed that histone deacetylace inhibitor (HDACI) valproic acid significantly improved hemodynamics, intestinal perfusion, and the survival rate after lethal burn shock. The mechanism may be attributable partly to the lowering of the level of proinflammatory factors, ameriolation of vasopermeability-induced visceral edema, reduction of blood volume loss, and protection of vital organs through inhibition of histone deacetylase activity of cell of vital organs.
Laboratory of Shock and Organ Dysfunction, Burns Institute, the First Hospital Affiliated to the People's Liberation Army General Hospital, 51 Fu Cheng Road, Beijing 100048, China.
Sen
S
Hu
Jing-Yuan
JY
Hou
Hai-Bin
HB
Wang
Mingxing
M
Yang
Zhi-Yong
ZY
Sheng
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002056:Burns / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D004285:Dogs; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006439:Hemodynamics / Q000502:physiology; D007413:Intestinal Mucosa / Q000098:blood supply; D023421:Models, Animal; D010421:Pentanoic Acids / Q000627:therapeutic use; D011897:Random Allocation; D012039:Regional Blood Flow; D012151:Resuscitation / Q000379:methods; D012769:Shock / Q000188:drug therapy; D016019:Survival Analysis; D014635:Valproic Acid / Q000627:therapeutic use*
D015415:Biomarkers; D004791:Enzyme Inhibitors; D010421:Pentanoic Acids; D014635:Valproic Acid