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.

Biologic determinants of dystrophic calcification and osteocalcin deposition in glutaraldehyde-preserved porcine aortic valve leaflets implanted subcutaneously in rats.

Bioprosthetic cardiac valve calcification is a frequent complication after long-term valve replacement. In this study the authors sought to examine the biologic determinants of this type of dystrophic calcification using subcutaneous implants of glutaraldehyde-preserved porcine aortic valve leaflets (GPVs) in rats. GPVs and clinical valvular bioprostheses were prepared identically. Retrieved implants were examined for calcification and the deposition of osteocalcin (OC), a vitamin K-dependent, bone-derived protein, that is found in other dystrophic and ectopic calcifications. GPVs implanted in 3-week-old rats calcified progressively (GPV Ca2+, 122.9 +/- 6.0 micrograms/mg) after 21 days, with mineral deposition occurring in a morphologic pattern comparable to that noted in clinical retrievals. Calcified GPVs accumulated osteocalcin (OC, 183.4 +/- 19.4 ng/mg); Nonpreserved porcine aortic leaflet implants did not calcify (Ca2+ + 5.6 +/- 1.0 micrograms/mg). Millipore diffusion chamber (0.45-mu pore size enclosed GPV implants accumulated calcium and adsorbed osteocalcin despite the absence of attached host cells. GPVs implanted for 21 days in 8-month-old rats calcified less (GPV Ca2+, 22.4 +/- 5.0 micrograms/mg) than did GPVs implanted in 3-week-old rats (see above). High-dose warfarin therapy (80 mg/kg) did not alter GPV calcification (GPV Ca2+, 39.6 +/- 2.9 micrograms/mg) in 72-hour subcutaneous implants in 3-week-old male rats, compared with control rats (GPV Ca2+, 40.8 +/- 4.8 micrograms/mg).