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 anticalcification 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 anticalcification 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.

Neomycin and pentagalloyl glucose enhanced cross-linking for elastin and glycosaminoglycans preservation in bioprosthetic heart valves

“…The main objective in this study was to investigate elastin stabilization in addition to GAG and collagen preservation in BHV leaflets. Our laboratory has developed multiple treatments to improve GAG stability in porcine heart valve leaflets, including the addition of neomycin, 4,10,12–16 carbodiimide cross-linking to replace GLUT 10,12,15,16,22 and periodate oxidation. 22,23 None of these treatments demonstrated improved stabilization against elasteolytic degradation.…”

“…Neomycin trisulfate is a hyaluronidase inhibitor which is cross-linked to the cusps, and has previously been shown to inhibit GAG loss in BHVs, but it was unable to stabilize elastin component. 12–16 PGG is derived from a plant polyphenol. It forms bonds with elastin via GLUT cross-linking to block enzyme-binding sites and improves elastin stability.…”

Calcification resistance for photooxidatively crosslinked acellular bovine jugular vein conduits in right‐side heart implantation

“…As myofibroblasts may lead to myofibroblast-associated calcification 18 and degradation of elastic fibers can result in elastin-oriented calcification, 10 an extended implantation time is needed to evaluate whether infiltrated myofibroblasts and degraded elastic fibers promote conduit calcification. Moreover, ethanol pretreatment facilitated inhibition of calcification in bioprosthetic valves, [19][20][21] and the effect of ethanol solutions used to sterilize BJVCs at preimplantation on BJVC calcification should be investigated.…”

Ethylene polymerization over supported titanium‐magnesium catalysts: Effect of polymerization parameters on the molecular weight distribution of polyethylene

“…As myofibroblasts may lead to myofibroblast‐associated calcification18 and degradation of elastic fibers can result in elastin‐oriented calcification,10 an extended implantation time is needed to evaluate whether infiltrated myofibroblasts and degraded elastic fibers promote conduit calcification. Moreover, ethanol pretreatment facilitated inhibition of calcification in bioprosthetic valves,19–21 and the effect of ethanol solutions used to sterilize BJVCs at preimplantation on BJVC calcification should be investigated.…”