THE RABBIT AS A MODEL FOR TESTING MATERIALS IMPLANTED INTO THE ARTERIAL BED

Highlights

• Additional risks associated with conducting preclinical testing in the rabbit model have been identified and thoroughly characterized.
• The methodology for conducting preclinical testing of materials implanted into the arterial bed in the rabbit model has been modified, encompassing all stages of the experiment – from anesthetic management to postoperative care.

Background. Preclinical in vivo testing is a mandatory stage in the development of high-risk medical devices intended for implantation into the human body. The selection of an appropriate experimental model is critical for obtaining reliable and reproducible results. Despite the widespread use of the rabbit model in vascular implant research, not all risks accompanying this study and arising from the characteristics of the chosen animal model have been described and corrected throughout the experiment – from anesthetic management to postoperative care.

Aim. To identify additional risks associated with preclinical testing of materials implanted into the arterial bed in a rabbit model and to modify the testing methodology by incorporating methods for correcting the identified risks.

Methods. The study was performed on rabbits (n = 11) of the Soviet Chinchilla breed (body weight 4.45 [4.3;4.8] kg). The test object was a semi‑tubular nitinol specimen. The protocol included premedication, induction and maintenance of anaesthesia with mechanical ventilation using retrograde intubation. Access to the thoracic aorta was achieved by left‑sided thoracotomy. After systemic heparinisation, a stepwise ischaemic preconditioning protocol was applied. The specimen was implanted through a longitudinal aortotomy. Postoperative management included oxygen therapy for 24 h, a five‑day course of antibiotics, analgesics and anticoagulants. On day 90, ultrasound examination of the implantation zone was performed to assess patency, flow velocity parameters and the presence of thrombotic masses, followed by euthanasia of the animals and tissue sampling for histological analysis.

Results. During the experiment (n = 11), the following complications were recorded: difficulty in performing intubation, paraplegia, and early postoperative respiratory failure. The modifications introduced included: optimization of animal positioning for intubation, implementation of stepwise ischemic preconditioning, reduction of occlusion time, performance of intercostal blockade, and administration of oxygen therapy during the first 24 hours after surgery. The modifications resulted in complete elimination of intubation-related and ischemic complications, and no early postoperative mortality occurred. In the surviving animals (n = 5) at 90 days, complete patency of the implantation zone was observed (peak systolic velocity 1.4 m/s, peak velocity ratio = 1), with no thrombosis, stenosis, or infection.

Conclusion. The implemented modifications (optimized retrograde intubation, stepwise ischemic preconditioning, and oxygen therapy within the first 24 hours) proved effective in chronic testing of arterial implants in rabbits, significantly reducing the complication rate. The identified critical points determine the directions for further protocol optimization.

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