Prevention of bioprosthetic heart valve calcification by ethanol preincubation: Efficacy and mechanisms

Narendra Vyavahare, Danielle Hirsch, Eyal Lerner, Jonathan Z. Baskin, Frederick J. Schoen, Richard Bianco, Howard S. Kruth, Robert Zand, Robert J. Levy

Research output: Contribution to journalArticlepeer-review

225 Scopus citations


Background: Calcification of the cusps of bioprosthetic heart valves fabricated from either glutaraldehyde cross-linked porcine aortic valves or bovine pericardium frequently causes the clinical failure of these devices. Our investigations studied ethanol pretreatment of glutaraldehyde cross- linked porcine aortic valves as a new approach to prevent cuspal calcification. The hypothesis governing this approach holds that ethanol pretreatment inhibits calcification resulting from protein structural alterations and lipid extraction. Methods and Results: Results 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) μg/mg tissue compared with control calcium level, 236.00±6.10 μg/mg tissue) and in sheep mitral valve replacements (ethanol-pretreated calcium level, 5.22±2.94 μg/mg tissue; control calcium level, 32.50±11.50 μg/mg tissue). The mechanism of ethanol inhibition may be explained by several observations: ethanol pretreatment resulted in an irreversible alteration in the amide I band noted in the infrared spectra for both purified type I collagen and glutaraldehyde cross-linked porcine aortic leaflets. Ethanol pretreatment also resulted in nearly complete extraction of leaflet cholesterol and phospholipid. Conclusions: Ethanol pretreatment of glutaraldehyde cross-linked porcine aortic valve bioprostheses represents a highly efficacious and mechanistically based approach and may prevent calcific bioprosthetic heart valve failure.

Original languageEnglish (US)
Pages (from-to)479-488
Number of pages10
Issue number2
StatePublished - 1997


  • calcium
  • collagen
  • surgery
  • valves


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