Al+++ binding studies and metallic cation effects on bioprosthetic heart valve calcification in the rat subdermal...

Al+++ preincubation has been shown to inhibit calcification of glutaraldehyde pretreated bovine pericardium calcification in the rat subdermal model. This study was designed to assess in vitro the Al+++ (10(-1) M, 10(-2) M, 10(-3) M preincubations) binding characteristics of glutaraldehyde pretreated bovine pericardium. In vivo studies assessed the ability of AlCl3 (10(-1) M, 10(-2) M, 10(-3) M) preincubations to inhibit calcification after 21 and 60 days in the rat subdermal model. Other in vivo studies investigated the ability of other metallic cations (Fe+++, La+++, and Ga+++) used as a pretreatment to inhibit glutaraldehyde pretreated bovine pericardium calcification after a 21 day rat subdermal implant. Lyophylized glutaraldehyde pretreated bovine pericardium samples were analyzed for Al+++ by neutron activation. In vitro results showed the greatest glutaraldehyde pretreated bovine pericardium Al+++ uptake in specimens incubated in 0.1M AlCl3. Maximal Al+++ uptake occurred by 1 hour. Glutaraldehyde pretreated bovine pericardium Al+++ levels after incubation in 10(-1) M, 10(-2) M, and 10(-3) M AlCl3 for 1 hour were 351.4 +/- 15.8 nM/mg, 96.4 +/- 17.4 nM/mg, and 24.6 +/- 4.9 nM/mg, respectively versus 394.5 +/- 48.0 nM/mg, 105.3 +/- 2.3 nM/mg, 40.0 +/- 8.8 nM/mg, respectively for 3 days. In vivo 21 day rat (50-60 g, male, Sprague-Dawley) subdermal implants of 0.1 M AlCl3, FeCl3, FeCl3 plus citrate, LaCl3, and GaNO3 pretreated glutaraldehyde pretreated bovine pericardium showed calcification inhibition by Al+++, Fe+++, and Fe+++ plus citrate (Ca++ = 5.5 +/- 0.2 micrograms/mg, 13.6 +/- 4.6 micrograms/mg, 5.9 +/- 1.7 micrograms/mg, respectively) compared to control (Ca++ = 63.6 +/- 5.7 micrograms/mg).(ABSTRACT TRUNCATED AT 250 WORDS)