Hirayama H, Xu X, Pang K S
Faculty of Pharmacy, University of Toronto, Ontario, Canada.
Am J Physiol. 1989 Aug;257(2 Pt 1):G249-58. doi: 10.1152/ajpgi.1989.257.2.G249.
Function and stability of vascularly perfused, recirculating in situ rat intestine (I) and intestine-liver (IL) preparations were evaluated in fasted and nonfasted rats because these techniques may be readily applied in drug metabolism studies. The rat intestine was perfused with blood medium (7.5 ml/min) via the superior mesenteric artery, with the venous outflow draining into the portal vein, which, together with hepatic arterial flow (2.5 ml/min), constituted the total blood flow (10 ml/min) to the liver. Maintenance of intestinal membrane integrity was observed. Rapid [14C]glucose absorption against a concentration gradient and a lack of [3H]-polyethylene glycol 4000 (PEG 4000, less than 4%) and Evans blue absorption by the recirculating I and IL preparations resulted after bolus injections of these markers into the pyloric end of the duodenum. Other indexes that revealed stable intestinal and liver functions were the following: preservation of reservoir perfusate volume, constancy in perfusion pressure, bile flow, and hemoglobin concentrations, evidence of intestinal glucose utilization and liver glucose production, and a lack of significant leakage of serum glutamic oxalic transaminase. The intestine and liver consumed oxygen at relatively constant rates, but the consumption rates for the fasted tissues (I or L) were significantly higher than those for nonfasted tissues. These results indicate that the vascularly perfused I and IL preparations were maintained in a viable and stable state for a 2-h perfusion period.
在禁食和非禁食大鼠中评估了血管灌注、循环原位大鼠肠道(I)和肠-肝(IL)制剂的功能和稳定性,因为这些技术可很容易地应用于药物代谢研究。通过肠系膜上动脉用血液培养基(7.5毫升/分钟)灌注大鼠肠道,静脉流出物排入门静脉,门静脉与肝动脉血流(2.5毫升/分钟)一起构成了肝脏的总血流(10毫升/分钟)。观察到肠膜完整性得以维持。在将这些标记物推注到十二指肠幽门端后,循环的I和IL制剂出现了逆浓度梯度的快速[14C]葡萄糖吸收,以及缺乏[3H]-聚乙二醇4000(PEG 4000,小于4%)和伊文思蓝吸收的情况。揭示肠道和肝脏功能稳定的其他指标如下:储液器灌注液体积保持不变、灌注压力、胆汁流量和血红蛋白浓度恒定、肠道葡萄糖利用和肝脏葡萄糖生成的证据,以及血清谷氨酸草酰乙酸转氨酶无明显渗漏。肠道和肝脏以相对恒定的速率消耗氧气,但禁食组织(I或L)的消耗速率显著高于非禁食组织。这些结果表明,血管灌注的I和IL制剂在2小时的灌注期内保持在存活且稳定的状态。