Dichloracetate Treatment to Prevent the Degeneration of Biological Cardiovascular Grafts

Objectives: Intima hyperplasia is a major issue of biological cardiovascular grafts resulting in progressive in vivo degeneration. Previously, dichloracetate (DCA) has been reported to prevent the formation of hyperplastic intima in injured arteries. In this study, the effect of DCA on the neointima formation and degeneration of decellularized implants was investigated in an aortic graft rat implantation model.

Methods: Detergent-decellularized donor rat aortic grafts (n = 22) were surface coated with fibronectin (50 µL/mL, 24 hours incubation) and implanted via anastomoses to the infrarenal aorta of the recipient rats. Rats in the DCA group (n = 11) received DCA via drinking water (0.75 g/dL), while rats without DCA treatment served as controls (n = 11). At 2 and 8 weeks, the grafts were explanted and examined by histology and immunofluorescence.

Results: Systemic DCA treatment inhibited neointima formation, resulting in a significantly reduced intima-to-media ratio (0.87 ± 0.06 vs. 1.97 ± 0.24 without DCA, p < 0.001). In addition, at 8 weeks, neointima calcification, as assessed by an established von Kossa staining-based score, was significantly decreased in the DCA group (anastomotic regions: A1: 0.2083 ± 0.1039 vs. 0.8500 ± 0.2927, p < 0.05; B2: 0.2083 ± 0.1343 vs. 0.8000 ± 0.2128, p < 0.05/nonanastomotic regions: A2: 0.0416 ± 0.0416 vs. 0.8000 ± 0.2865, p < 0.01; B1: 0.4167 ± 0.1694 vs. 1.200 ± 0.2575, p< 0.05). At 8 weeks, explanted grafts in both groups were luminally completely covered by an endothelial cell layer. In both groups, inflammatory cell markers (CD3, CD68) proved negative.

Conclusion: Systemic DCA treatment reduces neointima formation on decellularized arterial grafts, while allowing for rapid reendothelialization of the implants. Furthermore, DCA protected the grafts from calcification.