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Augmented sensitivity to benzodiazepine in septic shock rats

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Abstract

The purpose of this study was to assess the pharmacological characteristics of the benzodiazepine binding site in the brain of septic animals. We induced endotoxin shock in rats using a caecum ligation and puncture model. Following examination of the physiological state of the rats 24 hr after the caecum ligation and puncture, brain tissue samples were prepared for biochemical assay of amino acids and for the [3H]-diazepam radioligand binding assay. Amino acids assays indicated that the concentration of aromatic amino acids was higher in the CLP group (P < 0.05), the branched chain amino acid concentration was lower in the CLP group (P < 0.05) and the sulfur-containing amino acid concentration was elevated in the CLP group (P < 0.05) than in both the control and the shamoperated groups. [3H]-diazepam radioligand binding assays demonstrated that the number of receptors in the septic rats was increased in the forebrain (CLP rats; 2.37 ± 0.04 pmol · mg− 1 protein, control rats; 1.45 ± 0.02 pmol · mg− 1 protein, sham-operated rats; 1.49 ± 0.03 pmol · mg− 1 protein), cerebellum (CLP rats; 1.55 ± 0.05 pmol · mg− 1 protein, control rats; 1.05 ± 0.02 pmol · mg− 1 protein, sham-operated rats; 1.09 ± 0.02 pmol · mg− 1 protein) and brain stem (CLP rats; 1.21 ± 0.04 pmol · mg− 1 protein, control rats; 0.61 ± 0.02 pmol · mg− 1 protein, sham-operated rats; 0.63 ± 0.02 pmol · mg− 1 protein) compared with the control and shamoperated rats (P < 0.05). In conclusion, it was considered that the increased number of benzodiazepine receptors may be one cause of the neuronal alteration observed in septic shock animals.

Résumé

L’objectif de cette étude était d’évaluer chez des animaux septiques les caractéristiques pharmacologiques des récepteurs cérébraux des benzodiazépines. Les auteurs ont provoqué un choc septique en conformité avec un modèle de ligature et de perforation du caecum chez le rat. Après l’examen de l’état physiologique des rats 24 heures après la ligature du caecum et sa perforation, des échantillons de tissus cérébral ont été préparés pour une analyse biochimique des acides aminés et l’épreuve de liaison au radioligant [3H]-diazepam. Les épreuves de mesure des acides aminés ont montré que la concentration des acides aminés aromatiques était plus élevée dans le groupe CLP (P < 0,05), que la concentration des acides aminés à chaîne ramifiée était plus basse dans le groupe CLP (P < 0,05) et que la concentration des acides aminés sulfurés était plus élevée dans le groupe CLP comparativement au groupe contrôle et au groupe interventions factices. Les épreuves de liaison au radioligand [3H]-diazépam ont montré que le nombre de récepteurs chez les rats septiques était augmenté dans le proencéphale (rats CLP; 2,37 ± 0,04 pmol · mg− 1 de protéines, rats contrôles; 1,45 ± 0,02 pmol · mg− 1 de protéine, les rats opérés de façon factice; 1,49 ± 0,03 pmol · mg− 1 de protéine) dans le cervelet (rats CLP; 1,55 ± 0,05 pmol · mg− 1 de protéine, rats contrôles; 1,05 ± 0,02 pmol · mg− 1 de protéine, les rats opérés de façon factice; 1,09 ± 0,02 pmol · mg− 1 de protéine) et dans le bulbe (rats CLP; 1,21 ± 0,04 pmol · mg− 1 de protéine, rats contrôles; 0,61 ± 0,02 pmol · mg− 1 de protéine; rats opérés de façon factice; 0,63 ± 0,02 pmol · mg− 1 de protéine) comparativement aux contrôles et aux rats opérés de façon factice (P < 0,05). Pour conclure, les auteurs considèrent que l’augmentation des récepteurs des benzodiazepines pourrait être une cause de l’altération neurale observées chez les animaux en choc septique.

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Correspondence to Shigeru Saito.

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Komatsubara, T., Kadoi, Y. & Saito, S. Augmented sensitivity to benzodiazepine in septic shock rats. Can J Anaesth 42, 937–943 (1995). https://doi.org/10.1007/BF03011043

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Key words

  • complications: shock
  • infection: septicaemia
  • hypnotics: benzodiazepine