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Ann Thorac Surg 1988;46:309-316
© 1988 The Society of Thoracic Surgeons

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Articles

Inhibition of Bioprosthetic Heart Valve Calcification with Aminodiphosphonate Covalently Bound to Residual Aldehyde Groups

From the Division of Pediatric Cardiology, C. S. Mott Children's Hospital, University of Michigan Medical Center, Ann Arbor, MI, and the Departments of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA

Accepted for publication March 9, 1988.

^* Address reprint requests to Dr. Webb, Division of Pediatric Cardiology, Room 5014 Kresge II, The C. S. Mott Children's Hospital, University of Michigan Medical Center, Ann Arbor, MI 48109-0576.

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 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 µg/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.

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