Vascularly perfused rat small intestine: A research model for drug absorption.

Abstract

Abstract-Rat isolated small intestine was perfused at a fixed flow rate through the superior mesenteric artery with whole rat blood recycled from a devised oxygenator reservoir. As indicated by perfusion pressure, tissue glucose and oxygen consumption, and histological studies, the perfused intestine remained in a viable state over the perfusion period of 2 hr. Rapid absorption of glucose from the intestinal tract was observed after the intraduodenal injection. When single doses of acetaminophen were injected into the duodenal lumen or poured over the perfused intestine, the ab sorption was rapid and dose-dependent.Shortly after single intraduodenal injections of salicylamide, salicylamide in free and conjugated forms (sulfate and glucuronide) appeared in the circulating blood. These results indicate that the vascularly perfused intestinal preparation has wide applications in biochemical experimental fields.Numerous investigations have been concerned with attempts to develop useful pre parations for evaluating functions of the intestine. Most of these studies for uptake, me tabolism and transport of substrates by intestinal epithelial cells have been performed on isolated preparations immersed in physiological salt solution, e.g., intestinal rings, sheets of mucosa and serosa, and isolated villi (1-3). Although these preparations provided pertinent information leading to investigations of biochemical problems related to absorption and metabolism of drugs, there were drawbacks. Kavin et al. (4) and Windmueller et al. (5) devised an isolated intestinal preparation of the rat sustained by vascular perfusion with washed bovine red blood cells suspended in an "artificial plasma" and with rat whole blood, respectively, then carried out studies on viability. Their preparations appeared to be parti cularly suitable for examining entry of drugs from the intestinal tract into the blood or lymph vessels. However, most of the studies pertaining to drug absorption and metabolism have not been carried out in such preparations, and to our knowledge there is only one study, recently reported, which dealt with absorption of antipyrine, salicylic acid and urea (6).Thus, we examined absorption and metabolism of several drugs in the intestine, using the rat isolated small intestinal preparation sustained by perfusing the mesenteric vasculatures with whole rat blood recycled from a devised oxygenator-reservoir. MATERIALS AND METHODSMale Sprague-Dawley rats (130-150 g) were deprived of food overnight before the

Studies on the Viability of the Isolated Vascularly Perfused Rat Colon

“…In our experiments, the stabili ty of oxygen saturation in the venous effluent and of the calculated oxygen consumption demonstrated tissue via bility. In comparison with our results, other preparations utilizing red blood cells showed similar results [10,14,20] whereas lower oxygen consumption was measured using artifical oxygen carriers [16]. In accordance with our bio chemical viability parameters, the histology after 60 min revealed no obvious tissue damage.…”

“…Another critical parameter is glucose consumption. Comparing our results with established models of perfused small intestine, the values that we obtained with the colon were in the appropriate range [10,14,18] . The determination of lactate represents the rate of anaerobically metabolized glucose.…”

“…Some data were calculated refering to grants dry weight of colon tis sue (g dwgt). Calculations of glucose and oxygen consumption were performed as reported previously for the isolated perfused rat small intestine [10].…”

Pharmacodynamic and metabolism studies on a new coronary vasodilator,N-(2-hydroxyethyl) nicotinamide nitrate (SG-75).

“…Vascularly perfused, isolated intestine of the rat: After fasting overnight, rats weighing 130-150 g were anesthetized with pentobarbital sodium (65 mg/kg i.p.) and the small intestine was isolated, as described elsewhere (5). Briefly, the isolated small intestine was perfused with whole rat blood recycled from a devised oxygenator-reservoir at a fixed flow rate through the superior mesenteric artery.…”