Optimum Properties of Injectable Test Solutions for Intrathecal Administration to Conscious Rats.

Abstract

ABSTRACT. We devised a versatile intrathecal injection method enabling evaluation of central nervous system (CNS) toxicities in rats, and then explored appropriate physico-chemical properties for injectable test solutions at relatively large dosage volumes. In a preliminary bolus injection study, a 25-gauge needle was inserted into the subarachnoid space through the lateral aspect of the intervertebral portion between the 2nd and 3rd lumbar vertebra under light ether anesthesia. When 3% phthalocyanine blue solution, a vital dye, was injected in order to confirm its transfer to the brain tissue, the dye reached the cerebral ventricle, perivascular spaces and veins of the cerebral cortex. On the basis of these information, a fine polyethylene tube was introduced up to a level around the axis via a 20-gauge needle inserted in advance into the vertebral space by the same way. The needle was then withdrawn from the space leaving the tube filled with a test solution. After a full recovery from anesthesia, the infusion was commenced. Injection volume-versus-speed or osmolality-versus-pH relationship was assessed using solutions with various compositions, followed by monitoring mortality coupled with clinical signs. The tolerable combination of factors for the intrathecal solution without causing death was thought to be an injection volume up to 2 ml/rat with 300 mOsm/kg H 2 O, pH 3 to 7, at a injection speed of less than 0.5 ml/min, although minor clinical signs were observed. Pathological examination revealed pulmonary edema in dead animals, but no changes in surviving animals. This method applicable to conscious rats is considered to be simple and reliable, and does not require surgical operation and special equipment. The toxicological event in the intrathecal route seems to depend largely on the physico-chemical characteristics of the injectable solution. under these experimental conditions. -KEY WORDS: conscious condition, intrathecal injection, rat J. Vet. Med. Sci. 59(12): 1103-1107, 1997 ever been reported. We thus have devised an intrathecal injection method for conscious rats by combining previously stated techniques for mice [14] and rats [7,18,19], and then determined the suitable physico-chemical properties as its injectable test solutions. MATERIALS AND METHODS Animals:Male Sprague-Dawley rats aged 7 weeks with an average weight of 200-220 g were purchased from Japan S.L.C. Inc. (Hamamatsu, Shizuoka, Japan). The animals were housed 2 or 3 per wire-mesh cages in an airconditioned room (temperature, 23 ± 2°C; humidity, 55 ± 15%; light cycle, 12 hr/day) and allowed free access to commercial chow (F2, Funabashi Farm, Chiba, Japan) and tap water. Rats were acclimated to the laboratory environment for at least one week before use. All animals were treated humanely, and study protocols were in accordance with our institutional guideline for use of laboratory animals.Bolus injection procedure: Rats anesthetized with ether were placed in the prone position and an injection site was set in the lateral aspect of the...

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“…48 Injecting 1 mL of solution (pH ¼ 7, 300 mOsm/kg H 2 O) at 1 mL/min can be fatal in rats. 48 IT volumes injected in our study remained well below 1 mL. The speed of injection was approximately 1 mL/min and was achieved without any complications.…”