Synergistic inhibition of calcification of porcine aortic root with preincubation in FeCl3 and α-amino oleic acid in a rat subdermal model

Postimplant calcific degeneration is a frequent cause of clinical failure of glutaraldehyde crosslinked porcine aortic valve bioprostheses. We demonstrated pre- viously in rat subdermal and circulatory implants that a-amino oleic acid used as a bioprosthesis pretreatment was highly effective in mitigating aortic valve cusp but not aortic wall calcification. In this study we investigated the feasibility of synergistically applying two proven anticalcification agents (a-amino oleic acid and FeCl3) as pretreat- ments for mitigating both bioprosthetic cusp and aortic wall calcification. a-Amino oleic acid is hypothesized to prevent calcification by disrupting calcium phosphate formation kinetics, whereas suppression of alkaline phosphatase activity and ferric-phosphate com- plexation at cellular membrane initiation sites may be important factors in ferric ion's inhibition of calcification. In vivo implant studies (21-day rat subdermal model) indicated that individually FeCl3 (0.01 or 0.1 M for 24 h) or a-amino oleic acid (saturated solution) treatments were equally effective in mitigating cuspal calcification (tissue calcium levels: 30.2 { 10.2, 29.8 { 2.7, and 31.6 { 7.8 mg/mg tissue, respectively). However, sequential application of firsta-amino oleic acid and then FeCl3 synergistically reduced aortic wall calcification more effectively than either of the agents alone. The benefit of a synergistic application of two anticalcification treatments,a-amino oleic acid and FeCl3, was demon- strated. However, the synergistic effect was observed on aortic wall only at a higher FeCl 3 concentration (i.e., 0.1 M). q 1997 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 38: 43-48, 1997