Isovolumic hemodilution with dextran 40 in the rat: effect on the development of peripheral edema and various physiologic parameters. 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. 