Severe and progressive steatosis and focal necrosis in rat liver induced by continuous intragastric infusion of ethanol and low fat diet

A rat model of chronic ethanol intoxication was developed to study the effects of complete control of ethanol and nutrient intake on maintenance of blood alcohol levels (BAL). Double gastrostomy cannulas were implanted in male Wistar rats (350-400 g) to permit continuous intragastric alimentation and infusion of ethanol solution. Blood samples were obtained daily from central venous cannulas for determination of BAL and calculation of alcohol elimination rates. The daily ethanol dose was adjusted between 8 and 12 g/kg in an attempt to maintain a high degree of ethanol intoxication with a BAL between 100 and 300 mg/100 ml. The BAL averaged 216 +/- 120 (SD) mg/100 ml in 14 rats for 15-85 days, and exhibited a previously unreported, remarkable cyclical pattern independent of whether constant or variable dose was infused. In addition, the change in daily elimination rate of alcohol was significantly correlated (r = 0.67, p less than 0.0001) with the previous day's BAL. Furthermore, we identified a threshold BAL for each animal, above which a remarkable increase in elimination rate occurred. The variation in individual threshold levels (154.0-266.8 mg/100 ml) resulted in the wide range of mean BAL achieved. It appears that some secondary system or mechanism for alcohol metabolism is responsible for this cyclical phenomenon. We propose that this model will prove versatile and useful for further studies of in vivo alcohol metabolism.