Epoxy Compounds As a New Cross-Linking Agent for Porcine Aortic Leaflets: Subcutaneous Implant Studies in Rats

Abstract

The epoxy group of the epoxy compounds has an oxygen arm that can work as a flexible joint in a cross‐linking bridge and can block not only the amino group but also the carboxy group of collagen peptide. The purpose of this study is to evaluate the anticalcification efficacy of the epoxy compounds as a cross‐linking agent for xenograft bioprostheses. Porcine aortic leaflets were treated with 2% epoxy compounds and implanted in subcutaneous layer of 4‐week‐old rats. Measurement of calcium content showed that epoxy‐treated implants received a minimal calcification: mean 0.64μg/mg dry weight leaflet tissue (range 0.5–0.8;N=7) at 1 month; mean 0.94μg/mg (range 0.3–1.3;N=9) at 2 months; and mean 1.2μg/mg (range 0.5–2.1;N=10) at 3 months. Natural leaflets contained calcium of mean 0.43μg/mg. By contrast, glutaraldehyde‐preserved implants were severely calcified: mean 91μg/mg (range 41–130;N=11) at 1 month; mean 136μg/mg (range 73–205;N=16) at 2 months; and mean 170μg/mg (range 90–214;N=21) at 3 months. The epoxy compounds provide more pronounced anticalcification effects than the glutaraldehyde under pressure load‐free subcutaneous circumstances.

Mechanisms of the in vivo inhibition of calcification of bioprosthetic porcine aortic valve cusps and aortic wall with triglycidylamine/mercapto bisphosphonate

“…Previous studies by others have investigated poly-epoxy compounds for crosslinking bioprosthetic heart valves, with no definitive efficacy reported for preventing calcification [22][23][24][25]. This may have been due to the fact that these investigations were carried out with alkyl polyepoxides [22][23][24][25], rather than highly polar polyepoxides, such as TGA that was investigated in these studies.…”

“…This may have been due to the fact that these investigations were carried out with alkyl polyepoxides [22][23][24][25], rather than highly polar polyepoxides, such as TGA that was investigated in these studies. Alkyl-epoxides can have poor water solubility characteristics, and frequently require the use of organic co-solvents in order to obtain even partially aqueous solutions.…”

“…In Glut-prepared cusp and pericardium for bioprosthetic valve applications, some low level endogenous ALP has been demonstrated [22,23]. To understand the effect of TGA crosslinking on endogenous ALP activity in porcine cusp and porcine aortic wall, sections were examined for ALP activity as with the liver tissue mentioned above.…”

Histological Study of Right Ventricle-Pulmonary Artery Valved Conduit Implantation (RPVC) in Dogs with Pulmonic Stenosis

“…Conduit patency requires the following: the conduit must have antithrombotic properties [13]; intima hypertrophy must not progress in anastomoses between the MPA and the conduit [29], the intima should be covered with neo-endothelial cells [30] and the flexibility and histological form of the valve in the conduit should be maintained [27]. Although Denacol exerts an antithrombotic effect [19], intima hypertrophy in anastomoses has been demonstrated in humans due to delayed healing of the vessel after positioning a small-caliber artificial vascular graft treated with antithrombotics [22].…”

“…A bioprosthetic valved conduit has been used for RVOT reconstruction in humans [2]. Denacol-treated bioprosthetic implanted conduits are better assimilated and organized with the blood vasculature [19]; they are also thrombo-resistant and do not provoke the immune response [13]. Furthermore, the valve in the conduit might play an important role in preventing regurgitation from the PA to the RV in humans [26] and in dogs [16].…”