Controlled release of diphosphonate to inhibit bioprosthetic heart valve calcification: dose-response and mechanistic studies

摘要: Abstract Calcification is the Principal cause of clinical faliure bioprosthetic heart valves (BHV) fabricated from glutaraldehy de-treated porcine or bovine pericardium. This study examined dose—response local controlled-release disodium 1-hydroxyethylidene diphosphonic acid (EHDP) therapy for BHV calcification and its mechanism action. Controlled release EHDP ethylene—vinyl acetate matrices was regulated by co-incorporation insert filler inulin, subdermal cusps studied with co-implantation these in rats. Subdermal tissue inhibited vivo 7, 60, 84 days, without any adverse effects. At days (0.2, 2 20% w/w EHDP) co-implanted resulted explant levels 210.4, 39.1, 11.7 μg/mg comparison to control values 213.2 (a level equivalent that clinically failed BHV). The partition coefficient into unimplanted ( Ca 2+ = 1.23 μg / mg ) K p 0.57, increasing early (72 h implant, 19.6 , =1.6). diffusion through 0.8 × 10 −10 cm /s reflecting low permeability high affinity. It concluded both vitro suitable inhibit this effect most likely due interaction surface.