Petritsch W, Eherer A J, Holzer-Petsche U, Hinterleitner T, Beubler E, Krejs G J
Department of Internal Medicine, Karl Franzens University, Graz, Austria.
Gut. 1992 Sep;33(9):1174-8. doi: 10.1136/gut.33.9.1174.
In order to develop a model for secretory diarrhoea and to confirm the in vitro effects of cholera toxin in man in vivo the effect of intrajejunally administered cholera toxin was investigated in healthy volunteers. An intestinal perfusion technique with an occluding balloon proximal to the infusion site was used. The jejunum was perfused under steady state conditions with a plasma like electrolyte solution containing polyethylene glycol as a non-absorbable volume marker. After two control periods of one hour each, during which water was absorbed at a rate of 104 (14) (mean (SEM), n = 15) and 94 (15) ml/30 cm/h, respectively, three different doses of cholera toxin (6.25 micrograms, 12.5 micrograms, 25 micrograms) were administered by bolus into the lumen of the jejunum. Cholera toxin reduced absorption of water and electrolytes progressively over four hours and induced secretion in a dose dependent fashion. In the fourth hour net secretion amounted to 22 (23), 36 (24), and 88 (40) ml/30 cm/h (each n = five) with doses of 6.25, 12.5, and 25 micrograms cholera toxin, respectively. The movement of sodium, chloride, and bicarbonate paralleled water movement. Our results suggest that cholera toxin may serve as a secretory model in the human jejunum which might allow testing of new antisecretory agents.
为了建立分泌性腹泻模型并在人体中证实霍乱毒素的体内外效应,对健康志愿者进行了空肠内注射霍乱毒素的效应研究。采用在输注部位近端放置阻塞球囊的肠道灌注技术。在稳态条件下,用含有聚乙二醇作为不可吸收体积标志物的类似血浆的电解质溶液灌注空肠。在两个各持续一小时的对照期内,水的吸收速率分别为104(14)(均值(标准误),n = 15)和94(15)ml/30 cm/h,之后,将三种不同剂量的霍乱毒素(6.25微克、12.5微克、25微克)推注到空肠腔内。霍乱毒素在4小时内逐渐降低水和电解质的吸收,并以剂量依赖方式诱导分泌。在第4小时,霍乱毒素剂量为6.25、12.5和25微克时,净分泌量分别为22(23)、36(24)和88(40)ml/30 cm/h(每组n = 5)。钠、氯和碳酸氢盐的移动与水的移动平行。我们的结果表明,霍乱毒素可作为人体空肠的分泌模型,用于测试新的抗分泌药物。