An assessment of the suitability of a modified technique of in situ rat-liver perfusion for the study of certain hepatic drug-drug interactions.
A modified technique of in situ rat-liver perfusion has been developed. Minor modifications were made for practical purposes to an existing technique including: the use of sterile Krebs Henseleit buffer to reduce contamination of perfusion medium which inhibits perfusion rate at the end of a perfusion period; the use of erythrocytes from 5-10-day-old whole human blood to provide a lysis-free oxygen-carrying component of the perfusion medium; the introduction of a sampling and flow-rate device into the reservoir that allows repetitive and accurate monitoring of hepatic blood flow (+/- 0.1 ml/min) and also simplifies sampling of venous hepatic blood; a magnetic support for the hepatic portal vein cannula to provide an easily adjustable yet firm support for the cannula and thus reduce the risk of damage to the vessel wall. Various physiological parameters of the model were investigated. These include: bile flow rate; bile acid content of bile; K+, Na+, and Ca++ content of bile; percent of a bromosulphophthalein dose excreted; oxygen consumption of perfused livers; phenytoin disposition; glycogen content; acid phosphatase activity; and the fine structure of hepatocytes. These parameters were compared with literature and in vivo experimental values, and the results suggest that the model should be suitable for the study of metabolic drug-drug interactions occurring in the rat liver.
D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D001646:Bile / Q000502:physiology; D001647:Bile Acids and Salts / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D004347:Drug Interactions; D004912:Erythrocytes / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D008099:Liver / Q000378:metabolism* / Q000648:ultrastructure; D008102:Liver Circulation; D008111:Liver Function Tests; D008297:Male; D010101:Oxygen Consumption; D010477:Perfusion / Q000295:instrumentation; D010672:Phenytoin / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism; D013448:Sulfobromophthalein
D001647:Bile Acids and Salts; D013448:Sulfobromophthalein; D010672:Phenytoin; D006003:Glycogen; D012964:Sodium; D000135:Acid Phosphatase; D011188:Potassium; D002118:Calcium