Perez-Trepichio A D, Salgado A V, Jones S C
Department of Brain and Vascular Research, Cleveland Clinic Foundation, Ohio.
J Pharmacol Exp Ther. 1991 Mar;256(3):913-6.
Low molecular weight dextran 40 (D40), 40,000 daltons, is a potential therapeutic agent for cerebral ischemia because it increases local cerebral blood flow. However, the evaluation of D40 in the rat has been difficult due to systemic effects. We evaluated the effects of isovolumic hemodilution with D40 on the development of peripheral edema, mean arterial pressure, hematocrit (Hct) and total blood volume in 18 rats, during 30 min or 4 hr i.v. infusions, in animals with and without previous challenge with D40. Reduction of Hct without peripheral edema to a mean of approximately 31% was only achieved in the animals challenged with i.p. D40 24 hr before hemodilution and who received D40 over a period of 4 hr. Infusion of D40 over a period of 30 min was associated with shorter survival time, compared to the 4-hr infusion group (P less than .005). In the pretreated, rapidly infused group, total blood volume per body weight decreased significantly over time (P less than .005) and the mean arterial blood pressure dropped, but not significantly (P less than .07), whereas no change in Hct was detected and there was a trend toward increased peripheral edema, relative to the slowly infused groups. We conclude that reduction of Hct can be achieved successfully with i.p. administration of D40 24 hr before the study combined with infusion of the agent during a 4-hr period, without significant peripheral edema and early hypotension. This procedure should be used to avoid allergic reactions when evaluating hemodilution with D40 in rats.
低分子量右旋糖酐40（D40），分子量为40,000道尔顿，是一种潜在的脑缺血治疗药物，因为它能增加局部脑血流量。然而，由于其全身效应，在大鼠中评估D40一直很困难。我们评估了在18只大鼠中，在有或没有预先用D40激发的情况下，静脉输注D40进行等容血液稀释对周围性水肿、平均动脉压、血细胞比容（Hct）和总血容量在30分钟或4小时静脉输注期间的影响。只有在血液稀释前24小时腹腔注射D40且在4小时内接受D40输注的动物中，才实现了Hct降低而无周围性水肿，平均降至约31%。与4小时输注组相比，30分钟内输注D40与较短的生存时间相关（P小于0.005）。在预处理的快速输注组中，每体重的总血容量随时间显著降低（P小于0.005），平均动脉血压下降，但不显著（P小于0.07），而未检测到Hct变化，且相对于缓慢输注组，有周围性水肿增加的趋势。我们得出结论，在研究前24小时腹腔注射D40并在4小时内输注该药物，可以成功实现Hct降低，且无明显的周围性水肿和早期低血压。在评估大鼠用D40进行血液稀释时，应采用此程序以避免过敏反应。
