Abstract P1132: Cardiac Tissue Chip Model Of Arteriovenous-fistula-associated Hemodynamics Elicits Fibrotic Changes Seen In Mouse Model

Abstract

Introduction: Cardiovascular disease is the primary cause of death amongst end-stage renal disease (ESRD) patients. Though arteriovenous fistulas (AVFs) are the access of choice for hemodialysis, joining a high-pressure artery and low-pressure vein leads to cardiac volume overload acutely. Debate exists as to the cardiac ramifications of AVFs, due in part to the difficulty of recruiting ESRD patients and controls for prospective studies. Animal models have been essential in AVF studies, but their usefulness is limited by interspecies differences in physiology and other factors. Thus, we have developed a three-dimensional (3D) cardiac tissue chip with tunable pressure and stretch to model the acute hemodynamic changes associated with AVF creation. Hypothesis: In this study, we aimed to replicate the hemodynamics of murine AVF models in vitro and hypothesized that if 3D cardiac constructs were subjected to “volume overload”, they would display fibrosis and key gene expression changes seen in AVF mice. Methods: Mice underwent either AVF or sham procedure and were monitored for 28 d. Cardiac tissue constructs composed of h9c2 rat cardiac myoblasts and normal adult human dermal fibroblasts in hydrogel were seeded into devices and exposed for 96 h to 100 mmHg/10 mmHg pressure (0.4 s/0.6 s) at 1 Hz. "Systolic" pressure was generated via pneumatic pump while a hydrostatic pressure head gave rise to "diastolic" pressure. The controls were exposed to “normal” stretch while the experimental group was exposed to “volume overload”. Results and Conclusions: The in vitro model yielded similar fibrosis-related gene expression profiles (see figure) and patterns of fibrosis as the murine model.