Inhibition of calcification of glutaraldehyde pretreated porcine aortic valve cusps with sodium dodecyl sulfate: preincubation and controlled release studies.
Calcification of bioprosthetic heart valves fabricated from glutaraldehyde pretreated bovine pericardium or porcine aortic valves (PAV) is a frequent cause of the failure of these devices. Of all strategies considered thus far, only detergent preincubations using compounds such as sodium dodecyl sulfate (SDS) inhibited PAV bioprosthetic mineralization in circulatory sheep bioprosthetic valve replacements. The present study sought to characterize the mechanism of action of SDS preinicubation. Results of transport and material characterization studies showed that SDS had a relatively high affinity for PAV, with a maximum uptake of 167.1 +/- 6.8 micrograms SDS/mg tissue over 24 h at 37 degrees C with a partition coefficient of 19.3. The PAV diffusion of SDS was 1.95 +/- 0.35 10(-6) cm2/sec. The principal effect of SDS on PAV was phospholipid extraction. The residual organic phosphate in the SDS pretreated tissue was 2.22 +/- 0.72 nmol/mg tissue compared to the control untreated group with 18.52 +/- 2.1 nmol/mg tissue. Incubations of PAV specimens in a 1% SDS solution for 24 h significantly inhibited calcification after 21 days in subdermal implants in 3-week-old male rats (PAV Ca2+ = 18.0 +/- 11.8 micrograms/mg) compared to control (177.8 +/- 6.0 micrograms/mg). In contrast, coimplants of 30% SDS silicone rubber polymers, for regional sustained SDS administration, did not impede PAV calcification in 21 day implants Ca2+ = 166.0 +/- 14.0 micrograms/mg compared to the nondrug silicone matrix controls, Ca2+ = 173.0 +/- 6.6 micrograms/mg). Thus, we conclude that the mechanisms of SDS inhibition of PAV calcification is due to material effects which occur during preincubation, and is not facilitated by sustained SDS administration.
Hirsch
D
D
Department of Pediatrics, University of Michigan, Ann Arbor 48109.
Drader
J
J
Thomas
T J
TJ
Schoen
F J
FJ
Levy
J T
JT
Levy
R J
RJ
D000818:Animals; D001021:Aortic Valve / Q000187:drug effects*; D001672:Biocompatible Materials; D002114:Calcinosis / Q000517:prevention & control*; D002417:Cattle; D003692:Delayed-Action Preparations; D004058:Diffusion; D005976:Glutaral; D006350:Heart Valve Prosthesis; D008297:Male; D010743:Phospholipids / Q000302:isolation & purification; D019736:Prostheses and Implants; D011506:Proteins / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D012826:Silicone Elastomers; D012967:Sodium Dodecyl Sulfate / Q000008:administration & dosage*; D013552:Swine
D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D010743:Phospholipids; D011506:Proteins; D012826:Silicone Elastomers; D012967:Sodium Dodecyl Sulfate; D005976:Glutaral