Synergistic inhibition of calcification of porcine aortic root with preincubation in FeCl 3 and α-amino oleic acid in a rat subdermal model

Abstract

Postimplant calcific degeneration is a frequent cause of clinical failure of glutaraldehyde crosslinked porcine aortic valve bioprostheses. We demonstrated previously in rat subdermal and circulatory implants that α-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 (α-amino oleic acid and FeCl 3 ) as pretreatments for mitigating both bioprosthetic cusp and aortic wall calcification. α-Amino oleic acid is hypothesized to prevent calcification by disrupting calcium phosphate formation kinetics, whereas suppression of alkaline phosphatase activity and ferric-phosphate complexation 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 FeCl 3 (0.01 or 0.1 M for 24 h) or α-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 μg/mg tissue, respectively). However, sequential application of first α-amino oleic acid and then FeCl 3 synergistically reduced aortic wall calcification more effectively than either of the agents alone. The benefit of a synergistic application of two anticalcification treatments, α-amino oleic acid and FeCl 3 , was demonstrated. However, the synergistic effect was observed on aortic wall only at a higher FeCl 3 concentration (i.e., 0.1 M ). © 1997 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 38: 43–48, 1997