Nakagawa H, Groothuis D, Blasberg R G
Neurology. 1984 Dec;34(12):1571-81. doi: 10.1212/wnl.34.12.1571.
The RG-2 brain tumor model was used to determine whether unidirectional transport of alpha-aminoisobutyric acid (AIB) into brain and tumor tissue was increased after an intracarotid infusion of one of six different hypertonic solutions of L-arabinose. Intracarotid infusion of hypertonic solutions that have been reported as subthreshold for normal brain were used to determine whether they would selectively increase blood-to-tissue transport in brain tumors. No increase in the transport rate constant (K) across RG-2 tumor capillaries resulted from the infusion of 0.8- to 1.4-osm solutions. Infusions of 1.6- and 1.8-osm solutions were also performed, and blood-to-tissue transport was measured under conditions that produce maximum blood-brain-barrier disruption; however, no increase in the transport rate across tumor capillaries was measured. In brain regions surrounding the tumor, there was a trend toward increasing K values associated with increasing osmolality of the infusate, but the magnitude of this increase was small. There was a progressive increase in the K of tumor-free brain regions. This increase correlated with increasing osmolality of the infusate (0.8 to 1.8 osm). We conclude that intracarotid infusion of hypertonic solutions of L-arabinose does not increase the rate of delivery of water-soluble drugs to experimental RG-2 brain tumors. In this situation, the use of hypertonic infusions may be counterproductive and result in a greater delivery to and exposure of surrounding and normal brain tissue to levels of chemotherapeutic drugs which are potentially neurotoxic.
RG-2脑肿瘤模型用于确定在颈内动脉输注六种不同的L-阿拉伯糖高渗溶液之一后,α-氨基异丁酸(AIB)向脑和肿瘤组织的单向转运是否增加。使用已报道对正常脑为阈下浓度的高渗溶液进行颈内动脉输注,以确定它们是否会选择性增加脑肿瘤中的血-组织转运。输注0.8至1.4渗透压的溶液不会导致RG-2肿瘤毛细血管的转运速率常数(K)增加。还进行了1.6和1.8渗透压溶液的输注,并在产生最大血脑屏障破坏的条件下测量血-组织转运;然而,未测量到肿瘤毛细血管转运速率的增加。在肿瘤周围的脑区域,K值有随输注液渗透压增加而增加的趋势,但这种增加的幅度很小。无肿瘤脑区域的K值逐渐增加。这种增加与输注液渗透压的增加(0.8至1.8渗透压)相关。我们得出结论,颈内动脉输注L-阿拉伯糖高渗溶液不会增加水溶性药物向实验性RG-2脑肿瘤的递送速率。在这种情况下,使用高渗输注可能会适得其反,并导致更多的化疗药物递送至周围和正常脑组织并使其暴露于可能具有神经毒性的水平。