title: Neomycin fixation followed by ethanol pretreatment leads to reduced buckling and inhibition of calcification in bioprosthetic valves.
abstract: Glutaraldehyde crosslinked bioprosthetic heart valves (BHVs) have two modalities of failure: degeneration (cuspal tear due to matrix failure) and calcification. They can occur independently as well as one can lead to the other causing co-existence. Calcific failure has been extensively studied before and several anti-calcification treatments have been developed; however, little research is directed to understand mechanisms of valvular degeneration. One of the shortcomings of glutaraldehyde fixation is its inability to stabilize all extracellular matrix components in the tissue. Previous studies from our lab have demonstrated that neomycin could be used as a fixative to stabilize glycosaminoglycans (GAGs) present in the valve to improve matrix properties. But neomycin fixation did not prevent cuspal calcification. In the present study, we wanted to enhance the anti-calcification potential of neomycin fixed valves by pre-treating with ethanol or removing the free aldehydes by sodium borohydride treatment. Ethanol treatment has been previously used and found to have excellent anti-calcification properties for valve cusps. Results demonstrated in this study suggest that neomycin followed by ethanol treatment effectively preserves GAGs both in vitro as well as in vivo after subdermal implantation in rats. In vivo calcification was inhibited in neomycin fixed cusps pretreated with ethanol compared to glutaraldehyde (GLUT) control. Sodium borohydride treatment by itself did not inhibit calcification nor stabilized GAGs against enzymatic degradation. Neomycin fixation followed by ethanol treatment of BHVs could prevent both modalities of failure, thereby increasing the effective durability and lifetime of these bioprostheses several fold.
authors.affiliation: Department of Bioengineering, Cardiovascular Implant Research Laboratory (CIRL), Clemson University, Clemson, South Carolina 29634, USA.
authors.forename: Devanathan
authors.initials: D
authors.lastname: Raghavan
authors.forename: Sagar R
authors.initials: SR
authors.lastname: Shah
authors.forename: Naren R
authors.initials: NR
authors.lastname: Vyavahare
mesh_terms: D000818:Animals; D001705:Bioprosthesis; D002114:Calcinosis / Q000517:prevention & control*; D003094:Collagen / Q000737:chemistry; D017364:Collagenases / Q000378:metabolism; D000431:Ethanol / Q000008:administration & dosage*; D006025:Glycosaminoglycans / Q000032:analysis; D006350:Heart Valve Prosthesis; D009355:Neomycin / Q000008:administration & dosage*; D010196:Pancreatic Elastase / Q000378:metabolism; D051381:Rats; D013552:Swine
chemical_list: D006025:Glycosaminoglycans; D000431:Ethanol; D003094:Collagen; D010196:Pancreatic Elastase; D017364:Collagenases; D009355:Neomycin