A1 +++ Pretreatment Inhibits Calcification of Aortic Homografts Implanted Subcutaneously in rats
Phelps, Lisa L.
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Valved aortic homografts are often used to replace diseased cardiac valves. Calcification of these homograft valves may lead to clinical failure requiring reoperation. Preventing such calcification, therefore, presents an important challenge. The trivalent cation aluminum (Al+++) effectively inhibits calcification in bioprosthetic heart valve leaflets fabricated from glutaraldehyde pretreated porcine aorta or bovine pericardium subcutaneously implanted in rats, without adverse side effects. The objectives of this study were 1) to characterize calcification of aortic homografts in the rat subcutaneous model and 2) to assess the ability of Al+++ to inhibit homograft calcification. Thoracic aortas from 200-300 g Rattus norvegicus (male, CD, Sprague Dawley) were removed, washed, and incubated in AlCl3 solutions (0.01 M, 0.001 M, 0.0001 M) for one hour at 4 °C. The homografts were implanted subcutaneously in weanling rats (50-60 g) of the same species for 21 d. Control aortas were similarly removed from 200-300 g rats and implanted without pretreatment. The control aortic implants were retrieved periodically at 1,2,3,7, and 21 d. The explanted homografts were analyzed for calcium and aluminum content. The results showed that 1) aortic homografts not pretreated with Al+++ calcified severely at Ca++ levels comparable to those observed in bioprosthetic heart valve leaflets, 2) homograft preincubation in 0.01 M and 0.001 M AlCl3 significantly (p<0.05) inhibited calcification, and 3) no adverse side effects on somatic or bone growth occurred in rats implanted with AI+++ treated aortas. It is concluded that the rat subcutaneous model provides an effective method for studying characteristics of aortic homograft calcification and that aluminum (Al+++) can effectively inhibit homograft calcification without adverse effects.