Continuous Deep Intravenous Infusion in Rat Embryotoxicity Studies: The Effects of Infusion Volume and two Different Infusion Fluids on Pregnancy

Abstract

Intravenous infusion over long periods is an increasingly common method of administration for novel medicinal agents. This investigation was undertaken to evaluate the suitability of a new catheter implantation technique in the rat and to determine the effects of two different infusion fluids and volumes on litter parameters. Female Sprague-Dawley rats were anesthetized on day 1 of gestation and an indwelling catheter was implanted into the posterior vena cava by introduction into the femoral vein. A swivel joint in the roof of the cage allowed unrestricted movement of the animal. One group of rats was not treated further. Other groups were maintained on continuous infusion with physiological saline or isotonic glucose (dextrose) solution at various rates until day 15 of gestation (the test article would normally be dissolved in the infusion fluid starting from day 6 of gestation). Anesthesia and catheter implantation without infusion caused a slight transient reduction in maternal weight gain by comparison with historical data from untreated rats. This parameter then showed a clear inverse relationship to infusion volume in the infused groups. An infusion rate of 0.25 mL/h (i.e., 24 mL/kg day⁻¹) did not adversely affect gestation. Infusion of 1.0 mL/h of saline caused an increase in early resorption incidence and retarded fetal development. The same volume of isotonic glucose solution caused only a minor increase in resorptions with no effects on surviving fetuses.

Key Words: :

• Chronic intravenous infusion
• Teratology
• Embryotoxicity
• Pregnancy
• Rat