Inhibition of bioprosthetic heart valve calcification with aminodiphosphonate covalently bound to residual aldehyde groups

Journal Article · Thu Sep 01 00:00:00 EDT 1988 · Ann. Thorac. Surg.; (United States)

DOI:https://doi.org/10.1016/S0003-4975(10)65932-2· OSTI ID:6736539

Webb, C L; Benedict, J J; Schoen, F J; Linden, J A; Levy, R J

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.

• Research Organization: Univ. of Michigan Medical Center, Ann Arbor (USA)
• OSTI ID: 6736539
• Journal Information: Ann. Thorac. Surg.; (United States), Vol. 46:3
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
CALCINOSIS
INHIBITION
HEART
PROSTHESES
PHOSPHONIC ACID ESTERS
CHEMICAL BONDS
ALDEHYDES
CARBON 14 COMPOUNDS
CATTLE
COVALENCE
ELECTRONS
RATS
TRACER TECHNIQUES
ANIMALS
BODY
CARDIOVASCULAR SYSTEM
DOMESTIC ANIMALS
ELEMENTARY PARTICLES
ESTERS
FERMIONS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LEPTONS
MAMMALS
MEDICAL SUPPLIES
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
ORGANS
PATHOLOGICAL CHANGES
RODENTS
RUMINANTS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques