Infusion

A comprehensive look at infusion equipment and materials.

Tethered infusion is a commonly employed technique in laboratory animals, especially rats. Other small and large laboratory animal species are also used, but rats are the most common species used for this procedure, and the tethering apparatus essentially is the only option for long-term continuous access in rats. It is also possible to include withdrawal of blood and other body fluids with a tethered system, though this model is far less common than the tethered infusion model. In large animals, tetherless (“ambulatory”) models often are employed in order to reduce stress induced by tethers.¹ However, a lack of tetherless pumps for use in rats (except for the Mede- Cell pump) dictates virtually exclusive use of the tethered system in rat models. Due to the preponderance of tethered model use in rats, this article will focus on the technical details of tethered infusion in rats including the use of catheters, tethers, catheter and tether attachment devices, swivels, mounting hardware, and infusion pumps. Examples of techniques for body fluid withdrawal will also be discussed including discussion on the emergence of automated blood sampling devices.

Tethered Infusion and Withdrawal Apparatus
The tethered infusion and withdrawal models comprise the following components:

1. Catheter
2. Jacket, harness, button, and tail cuff for catheter and tether attachment to the animal
3. Tether spring and mounting hardware
4. Swivel
5. Pump for infusion
6. Tubing (animal-to-swivel and swivel-to-pump)
7. Automated blood sampling device for withdrawal

Catheter
In any infusion or withdrawal system, the catheter is the most critical component. A catheter failure likely results in dropping an animal from a study while failure of another component often can be resolved or replaced there by keeping an animal on study. Catheters have changed little since this model was introduced. The principal materials are silicone (SIL) and polyurethane (PU), though polyethylene (PE) and polyvinylchloride (PVC) are still used by some labs. The most significant change in catheters has been the use of a “rounded” or “tapered” distal (intravascular) tip and the addition of hemocompatible coatings such as heparin or lubricious coatings.

The material from which a catheter is constructed is an important consideration when planning an infusion study. The material of a catheter is important because of the following issues: hemocompatibility, test compound adsorption onto and absorption into the catheter, gas permeability, hardness, and the ability to coat with hemocompatible technologies. Table 1 depicts the key features of the most common catheter biomaterials.

While SIL, PE, and PVC were the predominant materials for many years, acceptance of PU has accelerated over the past two decades because of its good hemocompatibility, appropriate softness/stiffness balance, resistance to tears, and increased availability. PU is perhaps the most innately hemocompatible of these biomaterials (it is commonly used for artificial heart components). This PU hemocompatibility can be enhanced with the addition of coatings described later in this article. In addition to a catheter’s compatibility with a host, researchers must verify the catheter’s compatibility with any infusate. While most test compounds are compatible with the common catheter materials, certain compounds might absorb into or adsorb onto the material. Furthermore, other compounds might cause certain components in the catheter material to leach out of the catheter into the blood. Assessing this compound compatibility is done in vitro.