Prevention of calcification of bioprosthetic heart valve cusp and aortic wall with ethanol and aluminum chloride.

BACKGROUND: Calcification is frequently associated with device failure of bioprostheses fabricated from either glutaraldehyde pretreated porcine aortic valves or bovine pericardium. It was hypothesized that differential pretreatment with ethanol-aluminum chloride will prove safe and efficacious for inhibiting the calcification of both the porcine aortic valve bioprosthetic cusp and the aortic wall. METHODS: Glutaraldehyde-fixed porcine aortic valves were subjected to differential aluminum chloride (AlCl3) and ethanol pretreatment; aortic wall segments were treated exclusively with AlCl3 (0.1 moles/L) for 45 minutes, 6 hours, or 8 hours (groups 3A, B, and C, respectively), followed by valve cusp incubations in ethanol (80%, pH 7.4). Nontreated control bioprosthetic valves were either stent-mounted porcine aortic valve bioprostheses (Carpentier-Edwards, group 1) (Edwards, Santa Anna, CA) or St. Jude Toronto SPV valves (St. Jude Medical, St. Paul, MN) (group 2). Mitral valve replacements were carried out in juvenile sheep for 150 days. RESULTS: Calcium in cusps from group 3A was 2.84 +/- 0.62 mg calcium/g tissue versus control, 22.79 +/- 8.46 mg calcium/g tissue, p = 0.04. Valves pretreated with AlCl3 for 45 minutes, 6 hours, and 8 hours had significantly lower levels of calcium in the aortic wall compared to controls (40.38 +/- 5.66, 26.77 +/- 4.02, and 28.94 +/- 8.25 mg calcium/g tissue for groups 3A, 3B, and 3C, respectively, vs 95.47 +/- 17.14 mg calcium/g tissue for group 1, p < 0.001, and 133.42 +/- 3.96 mg calcium/g tissue for group 2, p < 0.001). CONCLUSIONS: Differentially applied ethanol and aluminum chloride pretreatment significantly inhibited calcification of both the glutaraldehyde-fixed porcine aortic valve bioprosthetic cusp and the aortic wall.

Calcification resistance with aluminum-ethanol treated porcine aortic valve bioprostheses in juvenile sheep.

BACKGROUND: Calcification of glutaraldehyde fixed bioprosthetic heart valve replacements frequently leads to the clinical failure of these devices. Previous research by our group has demonstrated that ethanol pretreatment prevents bioprosthetic cusp calcification, but not aortic wall calcification. We have also shown that aluminum chloride pretreatment prevents bioprosthetic aortic wall calcification. This study evaluated the combined use of aluminum and ethanol to prevent both bioprosthetic porcine aortic valve cusp and aortic wall calcification in rat subcutaneous implants, and the juvenile sheep mitral valve replacement model. METHODS: Glutaraldehyde fixed cusps and aortic wall samples were pretreated sequentially first with aluminum chloride (AlCl3) followed by ethanol pretreatment. These samples were then implanted subdermally in rats with explants at 21 and 63 days. Stent mounted bioprostheses were prepared either sequentially as previously described or differentially with AlCl3 exposure restricted to the aortic wall followed by ethanol pretreatment. Mitral valve replacements were carried out in juvenile sheep with elective retrievals at 90 days. RESULTS: Rat subdermal explants demonstrated that sequential exposure to AlCl3 and ethanol completely inhibited bioprosthetic cusp and aortic wall calcification compared with controls. However the sheep results were markedly different. The differential sheep explant group exhibited very low levels of cusp and wall calcium. The glutaraldehyde group exhibited little cusp calcification, but prominent aortic wall calcification. All sheep in the two groups previously described lived to term without evidence of valvular dysfunction. In contrast, animals in the sequential group exhibited increased levels of cusp calcification. None of the animals in this group survived to term. Pathologic analysis of the valves in the sequential group determined that valve failure was caused by calcification and stenosis of the aortic cusps. CONCLUSIONS: The results clearly demonstrate that a combination of aluminum and ethanol reduced aortic wall calcification and prevented cuspal calcification. Furthermore, this study demonstrates that exclusion of aluminum from the cusp eliminated the cuspal calcification seen when aluminum and ethanol treatments were administered in a sequential manner.