ETHANOL EXACERBATES HEPATIC MICROVASCULAR DYSFUNCTION, ENDOTOXEMIA, AND LETHALITY IN SEPTIC MICE

The effect of acute ethanol administration on the hepatic microvascula r responses to sepsis was studied. Polymicrobial sepsis was induced 30 min after mice had received ethanol (1 g/kg b.w.) or isocaloric malto se-dextrin by gastric gavage. Lethality within 24 h was 91.7% in the e thanol-treated animals and 40.0% in septic controls. Endotoxin levels in ethanol treated animals were 107 pg/ml at 6 hr and 1205 pg/ml at 12 h, compared with 32 pg/ml and 104 pg/ml, respectively in the controls . In vivo microscopy revealed that at 3 h in the ethanol treated septi c animals, Kupffer cell phagocytic activity was increased by 41%, wher eas the number of sinusoids containing blood flow were reduced by 34% concomitant with a 144% increase in the adherence of leukocytes to the sinusoidal walls when compared with the septic controls. By 6 h, howe ver, Kupffer cell phagocytic activity was reduced by 48% in the ethano l treated animals; this was accompanied by a further deterioration in sinusoidal blood flow. Thus, a small, acute dose of ethanol causes sig nificant impairment of the hepatic microcirculation followed by suppre ssion of Kupffer cell activity. This results in exacerbation of endoto xemia and lethality during polymicrobial sepsis.