Tsukamoto H, French S W, Reidelberger R D, Largman C
Alcohol Clin Exp Res. 1985 Jan-Feb;9(1):31-7. doi: 10.1111/j.1530-0277.1985.tb05046.x.
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.
为研究完全控制乙醇和营养摄入对维持血醇浓度（BAL）的影响，建立了慢性乙醇中毒大鼠模型。在雄性Wistar大鼠（350 - 400克）中植入双胃造瘘插管，以允许连续胃内营养和输注乙醇溶液。每天从中心静脉插管采集血样，用于测定BAL并计算酒精消除率。每日乙醇剂量在8至12克/千克之间调整，试图维持高度乙醇中毒状态，BAL在100至300毫克/100毫升之间。14只大鼠在15 - 85天内BAL平均为216±120（标准差）毫克/100毫升，并且呈现出一种先前未报道的显著周期性模式，与输注恒定剂量或可变剂量无关。此外，每日酒精消除率的变化与前一天的BAL显著相关（r = 0.67，p < 0.0001）。此外，我们确定了每只动物的BAL阈值，高于该阈值消除率会显著增加。个体阈值水平的变化（154.0 - 266.8毫克/100毫升）导致所达到的平均BAL范围很广。看来某种酒精代谢的次级系统或机制导致了这种周期性现象。我们认为该模型将被证明对体内酒精代谢的进一步研究具有通用性和实用性。
