Intraluminal Drug Delivery to the Mouse Arteriovenous Fistula Endothelium

Abstract

Delivery of therapeutic agents to enhance arteriovenous fistula (AVF) maturation can be administered either via intraluminal or external routes. The simple murine AVF model was combined with intraluminal administration of drug solution to the venous endothelium at the same time as fistula creation. Technical aspects of this model are discussed. Under general anesthesia, an abdominal incision is made and the aorta and inferior vena cava (IVC) are exposed. The infra-renal aorta and IVC are dissected for clamping. After proximal and distal clamping, the puncture site is exposed and a 25 G needle is used to puncture both walls of the aorta and into the IVC. Immediately after the puncture, a reporter gene-expressing viral vector was infused in the IVC via the same needle, followed by 15 min of incubation. The intraluminal administration method enabled more robust viral gene delivery to the venous endothelium compared to administration by the external route. This novel method of delivery will facilitate studies that explore the role of the endothelium in AVF maturation and enable intraluminal drug delivery at the time of surgical operation.

Hypoxia and hypoxia‐inducible factors promote the development of neointimal hyperplasia in arteriovenous fistula

“…Successful creation of the AVF was characterized by visible pulsatile arterial blood flow into the IVC. Pluronic F-127 gel (Sigma-Aldrich) has been used previously as a topical drug delivery system (Hashimoto et al 2016); thus, for in vivo experiments, drugs (DFO 50 mg kg -1 , Eve 0.1 mg kg -1 and TOPO 0.04 mg kg -1 ) were dissolved in 130 μL of pluronic gel (30% solution) to give a total volume of 170 μL and applied directly onto the vessels after haemostasis was obtained. For gene silencing, the small interfering RNA (siRNA) for HIF-1/2α (37.5 nm each) were mixed with polyethylenimine (PEI) and added to 15 μL of pluronic gel to give a total volume of 20 μL.…”