The effect of imidazole in endotoxin shock in dogs

The effect of imidazole, a thromboxane A2 inhibitor, in endotoxin shock in dogs was studied. Thromboxane A2 is a vasoconstrictor and enhances platelet and neutrophil aggregation. The purpose of this study was to examine the hemodynamic modifications of endotoxin shock with imidazole. Thirty dogs were studied, all receiving 1 X 10(8) live Escherichia coli/kg over a 30-minute period. The dogs were divided into three groups of ten dogs each. The first group received no treatment. The second group received a concomitant infusion of imidazole 25 mg/kg per hour. In a third group the imidazole infusion was delayed for 1 hour after the E. coli infusion. Mean arterial pressure (MAP), pulmonary wedge pressure (PWP), central venous pressure (CVP), cardiac output (CO), and systemic vascular resistance (SVR) were measured at 30-minute intervals. Hemoglobin (HGB), white blood count (WBC), a-A gradient (a-A grad), A-V 02 difference (AV02 diff), and fluid requirements were measured at 60-minute intervals. The endotoxin shock response in untreated control dogs was characterized by significant changes over time in MAP and SVR (decreased), and CO and a-A grad (increased). The imidazole group was significantly different, as the MAP and SVR did not decrease and the CO did not increase as in the control group. The control group required significantly more fluids than the imidazole group, while the HGB remained stable suggesting more capillary permeability in the control group. The delayed treatment group was statistically similar to the control animals. These data suggest that imidazole significantly modifies the hemodynamic response to endotoxin shock and may reduce the associated capillary permeability.(ABSTRACT TRUNCATED AT 250 WORDS)