Triglycidyl amine crosslinking combined with ethanol inhibits bioprosthetic heart valve calcification.

Triglycidyl amine crosslinking combined with ethanol inhibits bioprosthetic heart valve calcification.
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DOI:
10.1016/j.athoracsur.2011.04.104
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发表时间:
2011-09
影响因子:
4.6
通讯作者:
Levy, Robert J.
Levy, Robert J.
中科院分区:
医学2区
文献类型:
--
作者:
Connolly, Jeanne M.;Bakay, Marina A.;Alferiev, Ivan S.;Gorman, Robert C.;Gorman, Joseph H., III;Kruth, Howard S.;Ashworth, Paul E.;Kutty, Jaishankar K.;Schoen, Frederick J.;Bianco, Richard W.;Levy, Robert J.

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One of the most important factors responsible for the calcific failure of bioprosthetic heart valves is glutaraldehyde cross-linking. Ethanol (EtOH) incubation after glutaraldehyde cross-linking has previously been reported to confer anti-calcification efficacy for bioprostheses. The present studies investigated the anticalcification efficacy in vivo of the novel cross-linking agent, triglycidyl amine (TGA), with or without EtOH incubation, in comparison to glutaraldehyde. TGA cross-linking (+/− EtOH) was used to prepare porcine aortic valves for both rat subdermal implants and sheep mitral valve replacements, for comparisons with glutaraldehyde-fixed controls. Thermal denaturation temperature (Ts), an index of cross-linking, cholesterol extraction, and hydrodynamic properties were quantified. Explant endpoints included quantitative and morphologic assessment of calcification. Ts after TGA were intermediate between unfixed and glutaraldehyde-fixed. EtOH incubation resulted in almost complete extraction of cholesterol from TGA or glutaraldehyde-fixed cusps. Rat subdermal explants (90days) demonstrated that TGA-EtOH resulted in a significantly greater level of inhibition of calcification than other conditions. Thus, TGA-ethanol stent mounted porcine aortic valve bioprostheses were fabricated for comparisons with glutaraldehyde-pretreated controls. In hydrodynamic studies, TGA-EtOH bioprostheses had lower pressure gradients than glutaraldehyde-fixed. TGA-ethanol bioprostheses used as mitral valve replacements in juvenile sheep (150 days) demonstrated significantly lower calcium levels in both explanted porcine aortic cusp and aortic wall samples compared to glutaraldehyde-fixed controls. However, TGA-EtOH sheep explants also demonstrated isolated calcific nodules and intracuspal hematomas. TGA-EtOH pretreatment of porcine aortic valves confers significant calcification resistance in both rat subdermal and sheep circulatory implants, but with associated structural instability.
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