Beneficial actions of imidazole in endotoxin shock.

The effects of imidazole were studied in anesthetized cats during endotoxin shock. Imidazole (25 mg/hg/hr) was administered 30 minutes after intravenous injection of E. coli endotoxin (5 mg/kg). The degree of the severity of the shock state was assessed by mean arterial blood pressure (MABP), and by plasma cathepsin D and MDF activities. Analysis of thromboxane B2 concentrations during shock was also performed by radioimmunoassay. Administration of imidazole to cats given endotoxin partially prevented the decrease in MABP of endotoxin shock. Imidazole significantly prevented the increase in plasma cathepsin D and MDF activities. Thus, infusion of imidazole resulted in metabolic and hemodynamic improvement during endotoxin shock. The mechanism of imidazole protection appears to be via lysosomal membrane stabilization, stimulation of cardiac function and possibly by antagonizing the biochemical effects of endotoxin administration, rather than by inhibition of thromboxane synthesis. Data obtained using imidazole to block thromboxane synthesis in shock states must be interpreted with caution.