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Shwu-Fei Lee, Steven Sorden, Dale Dunn, Peter Sonnentag, Alexander Dwyer; Ocular Effects of Blood Collection Techniques in Rabbits. Invest. Ophthalmol. Vis. Sci. 2013;54(15):3039.
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Rabbits are commonly used in nonclinical safety evaluation of ophthalmic drugs. To reduce the number of animals, blood samples for toxicokinetic (TK) and toxicity tests are often taken from the same animals. Medial auricular artery catheterization is common when >4 TK timepoints are needed in one day. Potential catheterization-related ocular lesions occurred in previous rabbit studies. This study evaluated ocular effects of various blood collection techniques in rabbits.
50 female Hra:(NZW)SPF rabbits were assigned to 5 groups (10 animals/group). On Days 1 and 7, blood was collected at 7 timepoints in an 8-hour interval via repeated hypodermic needle puncture of a medial auricular artery (Group 1), a jugular vein (Group 2), or a combination of medial auricular artery and a jugular vein (Group 3); or via a medial auricular artery catheter (Group 4). Group 5 had a catheter without a needle taped to the surface of one pinna (control for Group 4, no blood collected). Clinical signs, dermal irritation at collection sites, body weight, and anatomic pathology were assessed.
Skin lesions or irritation at the collection/sham sites occurred in all groups. Jugular venipuncture sites had the most severe skin irritation and resulted in the fewest useable samples. Ear artery catheterization yielded the most useable samples and caused only minor skin lesions but was associated with multiple foci of necrosis/acute inflammation or subacute inflammation in Harderian and lacrimal glands. Findings correlated with catheter site, i.e., only animals with a catheter in the right ear had findings in right Harderian and/or lacrimal gland. Unilateral multifocal necrosis/acute inflammation in the mandibular salivary gland and focal degeneration/necrosis in the brain were also restricted to catheterized animals. Groups 1 and 3 only had microscopic lesions at intraartery sites. Group 2 had no technique-related microscopic lesions.
Repeated blood collection via ear artery catheter can result in foci of necrosis and inflammation in paraocular and mandibular salivary glands. Paraocular gland lesions could confound microscopic assessment of ophthalmic drugs. A combination of jugular vein and ear artery collections is a reasonable alternative with minimal samples missed. However, a satellite group for TK sample collections is recommended for ocular toxicity studies in rabbits.
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