Controlled release of 1-hydroxyethylidene diphosphonate: in vitro assessment and effects on bioprosthetic calcification in sheep tricuspid valve replacements
dc.contributor.author | Johnston, Thomas P. | en_US |
dc.contributor.author | Bove, Edward L. | en_US |
dc.contributor.author | Bolling, Steven F. | en_US |
dc.contributor.author | Boyd, James A. | en_US |
dc.contributor.author | Ciesliga, Barbara L. | en_US |
dc.contributor.author | Amidon, Gordon L. | en_US |
dc.contributor.author | Schoen, Frederick J. | en_US |
dc.contributor.author | Levy, Robert J. | en_US |
dc.date.accessioned | 2006-04-07T20:47:48Z | |
dc.date.available | 2006-04-07T20:47:48Z | |
dc.date.issued | 1989-06-01 | en_US |
dc.identifier.citation | Johnston, Thomas P., Bove, Edward L., Bolling, Steven F., Boyd, James A., Ciesliga, Barbara L., Amidon, Gordon L., Schoen, Frederick J., Levy, Robert J. (1989/06/01)."Controlled release of 1-hydroxyethylidene diphosphonate: in vitro assessment and effects on bioprosthetic calcification in sheep tricuspid valve replacements." International Journal of Pharmaceutics 52(2): 139-148. <http://hdl.handle.net/2027.42/27902> | en_US |
dc.identifier.uri | http://www.sciencedirect.com/science/article/B6T7W-4772M2K-73/2/663fae21989acac45e410664dad2ffc0 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/27902 | |
dc.description.abstract | Calcification (CALC) is the most frequent cause of the clinical failure of bioprosthetic valves (BHV's). Controlled-release (paravalvar) administration of the anticalcification agent ethanehydroxydiphosphonate (EHDP), as either Na2EHDP or in combination (1:1) with the less soluble CaEHDP, from a silicone rubber matrix (20% w/w EHDP) was studied both in vitro and in vivo for the prevention of BHV CALC. Seventeen sheep (6-7 months old, male, Suffolk) underwent tricuspid valve replacement using Hancock I, 25 mm porcine aortic bioprostheses. BHV explant evaluation after 16-20 weeks revealed that two of the 7 control BHV were calcified (139 +/- 20.8 [mu]gCa2+/mg of tissue), while none of the 9 BHV retrieved from animals receiving controlled release EHDP demonstrated CALC (4.41 +/- 1.09 [mu]g Ca2+/mg of tissue). No adverse effects of EHDP on bone or calcium metabolism were noted. The cumulative percent of EHDP released per electron microprobe analysis was 40.4% +/- 9.68 (Na, CaEHDP) to 79.0% +/- 4.82 (Na2EHDP) in vivo compared to 35.7% +/- 7.72 and 78.6 +/- 11.1 in vitro, respectively. Assessment of the Young's modulus (Y) using thermomechanical analysis (TMA) revealed a 1.5-fold (Silastic Q7-4840) to 9.5-fold (Silastic 382) increase in Y following drug loading. The Y for explanted, Silastic Q7-4840 polymer matrices ranged from 2.84 x 104 to 5.57 x 105 dyne/cm2. In vitro osmotic related matrix swelling of the Na2EHDP loaded, unsealed matrices (20% w/w) after 75 days was minimized to a 35.8% increase in weight due to coincorporation of CaEHDP with Na2EHDP in a 1:1 ratio and was further reduced (22.2% increase in weight) by sealing 76% of the releasing surface, compared to Na2EHDP matrices which demonstrated a 414% and 141% increase in weight, respectively. | en_US |
dc.format.extent | 800017 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.language.iso | en_US | |
dc.publisher | Elsevier | en_US |
dc.title | Controlled release of 1-hydroxyethylidene diphosphonate: in vitro assessment and effects on bioprosthetic calcification in sheep tricuspid valve replacements | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Pharmacy and Pharmacology | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Department of Pharmaceutics, College of Pharmacy, The University of Michigan, Ann Arbor, MI 48109, U.S.A.; Department of Pediatrics and Communicable Disease and Section of Thoracic Surgery, Division of Pediatric Cardiology, C.S. Mott Children's Hospital, U.S.A. | en_US |
dc.contributor.affiliationum | Department of Pharmaceutics, College of Pharmacy, The University of Michigan, Ann Arbor, MI 48109, U.S.A.; Department of Pediatrics and Communicable Disease and Section of Thoracic Surgery, Division of Pediatric Cardiology, C.S. Mott Children's Hospital, U.S.A. | en_US |
dc.contributor.affiliationum | Department of Pharmaceutics, College of Pharmacy, The University of Michigan, Ann Arbor, MI 48109, U.S.A.; Department of Pediatrics and Communicable Disease and Section of Thoracic Surgery, Division of Pediatric Cardiology, C.S. Mott Children's Hospital, U.S.A. | en_US |
dc.contributor.affiliationum | Department of Pharmaceutics, College of Pharmacy, The University of Michigan, Ann Arbor, MI 48109, U.S.A.; Department of Pediatrics and Communicable Disease and Section of Thoracic Surgery, Division of Pediatric Cardiology, C.S. Mott Children's Hospital, U.S.A. | en_US |
dc.contributor.affiliationum | Department of Pharmaceutics, College of Pharmacy, The University of Michigan, Ann Arbor, MI 48109, U.S.A.; Department of Pediatrics and Communicable Disease and Section of Thoracic Surgery, Division of Pediatric Cardiology, C.S. Mott Children's Hospital, U.S.A. | en_US |
dc.contributor.affiliationum | Department of Pharmaceutics, College of Pharmacy, The University of Michigan, Ann Arbor, MI 48109, U.S.A.; Department of Pediatrics and Communicable Disease and Section of Thoracic Surgery, Division of Pediatric Cardiology, C.S. Mott Children's Hospital, U.S.A. | en_US |
dc.contributor.affiliationum | Department of Pediatrics and Communicable Disease and Section of Thoracic Surgery, Division of Pediatric Cardiology, C.S. Mott Children's Hospital, U.S.A.; Department of Pharmaceutics, College of Pharmacy, The University of Michigan, Ann Arbor, MI 48109, U.S.A. | en_US |
dc.contributor.affiliationother | Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, U.S.A. | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/27902/1/0000322.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1016/0378-5173(89)90288-3 | en_US |
dc.identifier.source | International Journal of Pharmaceutics | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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