Extracellular matrix degrading enzymes are active in porcine stentless aortic bioprosthetic heart valves

Glutaraldehyde-fixed porcine aortic valve tissues are widely used for heart valve replacement surgery in the form of bioprosthetic heart valves (BHVs). The durability of BHVs in the clinical setting is limited by tissue degeneration, mechanical failure, and calcification. BHVs rely on the putative ability of glutaraldehyde to render biologic tissues metabolically inert and fully resistant to enzymatic attack. In the present study, we detected and partially characterized the activity of collagen and elastin-degrading enzymes in unimplanted, glutaraldehyde-fixed porcine aortic cusp and wall tissues and compared enzyme activities with those extracted from fresh tissues. Active enzymes capable of degrading extracellular matrix were found to be present in soluble form as well as immobilized on glutaraldehyde-crosslinked tissue matrix. Total levels of collagenolytic activities were evaluated to approximately 0.25 microg of degraded collagen/mg of dry tissue/24 h for both glutaraldehyde-fixed wall and cusp tissues. A major finding of this study was the ability of soluble tissue enzymes to partially degrade glutaraldehyde-fixed collagen and particularly large amounts of glutaraldehyde-fixed elastin. These calcium-dependent gelatinases share many biochemical similarities with matrix metalloproteinases. These data strongly indicate that glutaraldehyde-fixed porcine valvular tissues are not metabolically inert and are not entirely resistant to enzymatic attack, thereby rendering BHVs vulnerable to biologic degeneration and subsequent chronic failure.