PREVENTION OF BIOPROSTHETIC HEART-VALVE CALCIFICATION BY ETHANOL PREINCUBATION - EFFICACY AND MECHANISMS

Background Calcification of the cusps of bioprosthetic heart valves fa bricated from either glutaraldehyde cross-linked porcine aortic valves or bovine pericardium frequently causes the clinical failure of these devices. Our investigations studied ethanol pre treatment of glutaral dehyde cross-linked porcine aortic valves as a new approach to prevent cuspal calcification. The hypothesis governing this approach holds th at ethanol pretreatment inhibits calcification resulting from protein structural alterations and lipid extraction. Methods and Results Resul ts demonstrated complete inhibition of calcification of glutaraldehyde -pretreated porcine bioprosthetic aortic valve cusps by 80.0% ethanol in rat subdermal implants (60-day ethanol-pretreated calcium level, 1. 87+/-0.29 mu g/mg tissue compared with control calcium level, 236.00+/ -6.10 mu g/mg tissue) and in sheep mitral valve replacements (ethanol- pretreated calcium level, 5.22+/-2.94 mu g/mg tissue; control calcium level, 32.50+/-11.50 mu g/mg tissue). The mechanism of ethanol inhibit ion may be explained by several observations: ethanol pretreatment res ulted in an irreversible alteration in the amide I band noted in the i nfrared spectra for both purified type I collagen and glutaraldehyde c ross-linked porcine aortic leaflets. Ethanol pretreatment also resulte d in nearly complete extraction of leaflet cholesterol and phospholipi d. Conclusions Ethanol pretreatment of glutaraldehyde crosslinked porc ine aortic valve bioprostheses represents a highly efficacious and mec hanistically based approach and may prevent calcific bioprosthetic hea rt valve failure.