Factors influencing calcification of cardiac bioprostheses in adolescent sheep

Objective: We determined the possible effects of age, antimineralization treatments, circulatory implant conditions, prosthesis design, and valve-related structural aspects on valve calcification in adolescent sheep. Methods: Calcium content was measured by means of atomic absorption spectrometry in bioprostheses implanted in 120 sheep ( age < 1 year) for a period of 3 or 6 months. Results: Bioprostheses calcified significantly in adolescent sheep, but the extent of calcification was multifactorial. Multivariate analysis of the calcium content reveals that age, mitral or pulmonary implant position, prosthesis design ( stented or stentless), structure ( porcine or pericardial, wall portion or cusp), and antimineralization treatment are independent factors influencing calcification; implant duration beyond 3 months was not. In juvenile sheep ( age 5 months) the wall portion, as well as the cusps of the prosthesis, calcified significantly more than in adolescent sheep ( age 11 months). Irrespective of age, the cusps of valves implanted in the mitral position calcified more than those in the pulmonary position. The wall portion of stentless valves calcified more than that of stented valves, and pericardial valves calcified less than porcine valves. The surfactant ( Tween 80, No-React, and alpha-amino-oleic acid) and alcohol ( ethanol and octanediol) treatment significantly reduced cusp calcification; sodium dodecylsulfate did not. None of the anticalcification treatments was able to prevent wall calcification in stentless porcine valves. Conclusion: These findings suggest that tissue valve calcification is determined by many independent factors, which can be identified by using adolescent sheep as a preclinical in vivo model.