An alteration in the gamma-aminobutyric acid receptor system in experimentally induced septic shock in rats

Objective To investigate the role of the brain gamma-aminobutyric acid receptor system in septic shock. Design Prospective, controlled study. Setting Animal laboratory. Subjects Twenty-one male Wistar rats (7 wks old) were randomized to three groups: group 1 (n equals 7, control); group 2 (n equals 7, sham-operated); group 3 (n equals 7, cecal ligation and puncture group). Interventions Under light ether anesthesia, the rats were treated as described above. Twenty-four hours after treatment, the rats were killed by decapitation. Plasma amino acid concentrations were measured using the collected blood. The brain was excised as rapidly as possible, and separated into forebrain, cerebellum, and brain stem. The brain gamma-aminobutyric acid concentration was measured at each of the three regions. Using3 H-musimol, which is a gamma-aminobutyric acid receptor agonist, as a radioligand, the gamma-aminobutyric receptor densities were measured in these three regions by a radio-receptor assay. Measurements and Main Results The concentrations of the branch-chain amino acids (leucine, isoleucine, valine) were lower in the cecal ligation and puncture group than in the control and sham-operated groups. The concentrations of the sulfur-containing amino acids (cysteine and taurine) were increased in the cecal ligation and puncture group compared with the other two groups, but the methionine concentration was increased in the shamoperated and the cecal ligation and puncture groups compared with the control group (p less than .05). The plasma gamma-aminobutyric acid concentration was not detectable in any of the three groups. The ammonia concentration was greater in the cecal ligation and puncture group than in the other two groups. There was no significant difference in the brain gamma-aminobutyric acid concentration among the three groups. The maximum number of binding sites in the forebrain of the cecal ligation and puncture group was higher than in the other two groups at both high-and low-affinity sites (control group: high-affinity sites 0.34 plus minus 0.03, low-affinity sites 2.93 plus minus 0.28; shamoperated group: high-affinity sites 0.35 plus minus 0.03, low-affinity sites 2.73 plus minus 0.18; cecal ligation and puncture group: high-affinity sites 0.59 plus minus 0.13, low-affinity sites 3.53 plus minus 0.21; mean plus minus SEM pmol/mg protein) (p less than .05). There were no significant differences observed in other regions of the brain (cerebellum and brain stem) in the three groups. The dissociation constants for3 H-musimol were almost unchanged in the three groups. Conclusions An increase in the gamma-aminobutyric acid-A receptor density was observed in the forebrain of the cecal ligation and puncture model rats. This alteration may be closely related to the pathogenesis of brain dysfunction during septic shock. (Crit Care Med 1996; 24:298-305)