Retardation of calcification of bovine pericardium used in bioprosthetic heart valves by phosphocitrate and a synthetic analogue.
The purpose of this study was to determine if phosphocitrate (PC), a naturally occurring inhibitor of calcification, and its synthetic analogue, N-sulpho-2-amino tricarballylate (SAT), administered either by daily injection or local delivery via Alzet osmotic minipump, could inhibit calcification of glutaraldehyde-preserved bovine pericardium used in bioprosthetic heart valves, subcutaneously implanted in rats. Local drug delivery, but not systemic administration, was effective. PC, administered by Alzet minipump (12 mg.kg-1.day-1), inhibited calcification significantly (tissue calcium = 5 +/- 2 micrograms/mg dry tissue, mean +/- SEM), compared with untreated or saline-treated controls (89 +/- 9 and 49 +/- 9 micrograms/mg, respectively). SAT, administered by the same route at both the same and a higher molar dosage, was less potent (tissue calcium = 26 +/- 9 micrograms/mg and 17 +/- 5 micrograms/mg, respectively). PC and SAT therapy were not associated with adverse effects. We conclude that locally administered PC and SAT can inhibit intrinsic calcification of bovine pericardium, with PC being more potent.
Tsao
J W
JW
Department of Pathology, Brigham and Women's Hospital, Boston.
Schoen
F J
FJ
Shankar
R
R
Sallis
J D
JD
Levy
R J
RJ
D000818:Animals; D001672:Biocompatible Materials; D002114:Calcinosis / Q000517:prevention & control*; D002417:Cattle; D002951:Citrates / Q000494:pharmacology*; D006132:Growth Plate / Q000187:drug effects; D006350:Heart Valve Prosthesis; D008297:Male; D010496:Pericardium / Q000187:drug effects / Q000473:pathology* / Q000637:transplantation; D051381:Rats; D011919:Rats, Inbred Strains; D014233:Tricarboxylic Acids / Q000494:pharmacology*
D001672:Biocompatible Materials; D002951:Citrates; D014233:Tricarboxylic Acids; C014148:phosphocitrate; C039013:N-sulfo-2-aminotricarballylate