Inhibition of bioprosthetic heart valve calcification with aminodiphosphonate covalently bound to residual aldehyde groups.
Calcification is the principal mode of failure of bioprosthetic heart valves (BPHV) fabricated from glutaraldehyde-pretreated porcine aortic valves or bovine pericardium. Covalent binding of aminopropanehydroxy-diphosphonate (APDP) to residual glutaraldehyde in pericardial BPHV tissue was studied as an approach for the inhibition of calcification. BPHV tissue was preincubated in 0.14 M APDP at pH 7.4, 9.0, and 11.0 for various durations (1 hour to 8 days). The need for NaBH4 stabilization of the tissue-bound APDP was also examined in vitro. The bound APDP was determined using 14C-labeled APDP. APDP uptake was dependent on incubation duration and pH. Calcification of APDP-pretreated BPHV was studied using 21-day rat subdermal implants. Calcification inhibition was directly related to the amount of tissue APDP incorporation. Inhibition of calcification to less than 15% of control was achieved with a concentration of bound APDP of greater than or equal to 30 nM/mg dry tissue with more than 1 hour of incubation at pH 11.0 (bound APDP, 33.55 nM/mg; BPHV calcium content = 3.1 +/- 0.9 micrograms/mg). No adverse effects such as rat growth inhibition or disruption of bone architecture were observed after any treatment. Additionally, in vitro, NaBH4 stabilized tissue-bound APDP. In conclusion, APDP covalently bound to residual aldehyde functions markedly inhibited calcification of BPHV tissue. This inhibition was dependent on the amount of APDP incorporated. NaBH4 stabilized APDP-glutaraldehyde covalent bonds.
D000447:Aldehydes / Q000378:metabolism*; D000818:Animals; D001024:Aortic Valve Stenosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D001705:Bioprosthesis; D002114:Calcinosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002417:Cattle; D004164:Diphosphonates / Q000378:metabolism* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004583:Electrons; D012968:Etidronic Acid; D005976:Glutaral; D006350:Heart Valve Prosthesis; D008297:Male; D000077268:Pamidronate; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000447:Aldehydes; D004164:Diphosphonates; D012968:Etidronic Acid; D000077268:Pamidronate; D005976:Glutaral