Method of intra-arterial drug administration in a rat: Sex based optimization of infusion rate.

ABSTRACT

BACKGROUND: Endovascular thrombectomy is the process of removing a blood clot and re-establishing blood flow in patients with emergent large vessel occlusion. The technique provides an opportunity to deliver therapeutics directly to the site of injury. The intra-arterial (IA) route of drug administration in the mouse was developed to bridge the gap between animal stroke treatments and clinical stroke therapy. Here, we adapted the IA method for use in rats, by investigating various flow rates to optimize the IA injection through the internal carotid artery (ICA). METHODS: Male and female Sprague-Dawley rats (∼4 months of age) were subjected to placement of micro-angio tubing at the bifurcation of the common carotid artery for injection into the ICA. We evaluated a range of infusion rates of carbon black ink and its vascular distribution within the brain. RESULTS: Optimal injection rates in males was 4-6 µl/min and 2-4 µl/min in females. The IA injection using these sex-specific rates resulted in appropriate limited dye delivery to only the ipsilateral region of the brain, without inducing a subarachnoid hemorrhage. CONCLUSION: Upon adapting the IA administration model to rats, it was determined that the rate of infusion varied between males and females. This variability is an important consideration for studies utilizing both sexes, such as in ischemic stroke studies.