(G-272) Investigation of Effects of AVF Hemodynamics on Drug-Coated Balloon Treatment

Introduction:Since 2017, when drug-coated balloons (DCBs) first received FDA indication for use in dysfunctional arteriovenous fistula (AVF) hemodialysis accesses, their drug delivery performance in the AVF environment still have not been extensively studied. This vascular region experiences considerably higher blood flow rates and shear stress than the coronary and peripheral arterial systems, for which DCBs were originally designed. Therefore, an ex vivo bioreactor system was developed to simulate AVF hemodynamics using porcine carotid arteries to allow for studying the impact of these extreme hemodynamics on DCB performance and drug retention.
Materials and Methods: The bioreactor was developed consisting of a gear pump, uses a signal generator to create a pulsatile flow, and circulates DMEM media in a closed system. The test section was a freshly harvested porcine carotid artery. Commercially available IN.PACT Admiral Paclitaxel-coated DCBs were deployed in the carotid arteries under normal arterial flow or AVF flow. DCBs were inflated to 15-20% overstretch of the arterial diameter and deployed for 120 seconds. Vessels were collected 1 hour and 24 hours (n = 3 per experimental group) after drug delivery for liquid chromatography with tandem mass spectrometry (LC-MS-MS) pharmacokinetic analysis. Two-tailed unpaired t-tests were used to compare corresponding groups. All data are expressed as mean ± standard deviation.
Results, Conclusions, and Discussions: The average arterial flow rate was 120 ± 18 mL/min and the systolic/diastolic pressures were 138/22 mmHg. The average AVF flow rate measured in the bioreactor system was 665 ± 85 mL/min, with systolic/diastolic pressures of 146/87 mmHg. At 1-hour, tissue drug concentrations in arteries treated under arterial flow vs. AVF flow were 102.22 ± 81.70 ng/mg and 113.82 ± 36.21 ng/mg, respectively (p = 0.833). At 24-hours, the tissue concentrations were 29.52 ± 27.91 ng/mg in arteries under arterial flow and 100.52 ± 86.28 ng/mg in arteries under AVF flow (p = 0.246). Under arterial flow, there was a 71.1% decrease in drug concentration (p = 0.218) from 1 to 24 hours. Under AVF flow, a 11.7% decrease was found (p = 0.817) from 1 to 24-hours. Summary of this data is shown in Figure 1.

At 1- and 24-hours, no observable differences were observed between arterial and AVF flow. Additionally, no observable differences were found between 1- and 24-hour time points in either flow group.

Trends in the data suggest the AVF hemodynamics may increase retention of DCB-delivered paclitaxel in the arterial tissue compared to arterial tissue. Future investigation in the research includes modifying the bioreactor to resemble the AVF anatomy and physiology by fusing arterial and venous tissue.


Acknowledgements (Optional): Thank you to the members of Dr. Yazdani’s lab for their help and support. This work was supported by the National Institute of Health [1R01EB028798].
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