Quarles J M, Belding R C, Beaman T C, Gerhardt P
Infect Immun. 1974 Mar;9(3):550-8. doi: 10.1128/iai.9.3.550-558.1974.
Hemodialysis was employed to simulate in vivo conditions for growth in mammalian blood, but without phagocytosis, by using the goat and Serratia marcescens as a host-parasite model. The blood stream was shunted surgically via prosthetic tubing from a carotid artery through the hollow-fiber membranes in an artificial kidney hemodialyzer and back into a jugular vein. The dialysate solution concurrently was pumped from a modular fermentor through the hemodialyzer jacket outside of the membranes and back into the fermentor. Hemodialysis between the two circuits was maintained continuously. When equilibrium was attained, bacteria inoculated into the dialysate circuit multiplied first exponentially at the maximal rate and then arithmetically at a lesser rate equally well under aerobic or anaerobic conditions. When a population of about 10(9) viable bacteria/ml was exceeded, the goat reacted acutely with signs of general toxemia, pyrexia, and leukopenia, apparently because of dialyzable toxic material produced by the culture. The maximal molecular size of the toxic material was defined relative to a rigid globular protein of 15,000 in molecular weight and 1.9 nm in hydrodynamic radius or to a flexible fibrous polyglycol of 5,500 in molecular weight and 2.6 nm in hydrodynamic radius, based on determinations of the membrane porosity threshold for dialysis.
通过使用山羊和粘质沙雷氏菌作为宿主 - 寄生虫模型，采用血液透析来模拟哺乳动物血液中生长的体内条件，但不涉及吞噬作用。血流通过人工肾血液透析器中的中空纤维膜，经手术通过假体管道从颈动脉分流，再回到颈静脉。同时，透析液从模块化发酵罐泵入，通过膜外部的血液透析器夹套，再回到发酵罐。两个回路之间的血液透析持续进行。达到平衡时，接种到透析液回路中的细菌首先以最大速率呈指数增长，然后在有氧或无氧条件下以较低速率呈算术增长。当每毫升活菌数量超过约10⁹时，山羊会出现急性反应，表现为全身毒血症、发热和白细胞减少的症状，这显然是由于培养物产生的可透析有毒物质所致。基于对透析膜孔隙率阈值的测定，有毒物质的最大分子大小相对于分子量为15,000、流体动力学半径为1.9 nm的刚性球状蛋白质，或相对于分子量为5,500、流体动力学半径为2.6 nm的柔性纤维状聚乙二醇来定义。
