title: Prevention of bioprosthetic heart valve calcification by ethanol preincubation. Efficacy and mechanisms.
abstract: 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.
  
  
  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 micrograms/mg tissue compared with control calcium level, 236.00 +/- 6.10 micrograms/mg tissue) and in sheep mitral valve replacements (ethanol-pretreated calcium level, 5.22 +/- 2.94 micrograms/mg tissue; control calcium level, 32.50 +/- 11.50 micrograms/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.
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor 48109-0576, USA.
authors.forename: N
authors.initials: N
authors.lastname: Vyavahare
authors.forename: D
authors.initials: D
authors.lastname: Hirsch
authors.forename: E
authors.initials: E
authors.lastname: Lerner
authors.forename: J Z
authors.initials: JZ
authors.lastname: Baskin
authors.forename: F J
authors.initials: FJ
authors.lastname: Schoen
authors.forename: R
authors.initials: R
authors.lastname: Bianco
authors.forename: H S
authors.initials: HS
authors.lastname: Kruth
authors.forename: R
authors.initials: R
authors.lastname: Zand
authors.forename: R J
authors.initials: RJ
authors.lastname: Levy
mesh_terms: D000818:Animals; D001705:Bioprosthesis; D002114:Calcinosis / Q000517:prevention & control*; D002417:Cattle; D003094:Collagen / Q000737:chemistry; D003432:Cross-Linking Reagents / Q000494:pharmacology; D062109:Dermatologic Surgical Procedures; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D005976:Glutaral / Q000494:pharmacology; D006350:Heart Valve Prosthesis; D008055:Lipids / Q000302:isolation & purification; D008943:Mitral Valve / Q000601:surgery; D008968:Molecular Conformation; D009994:Osmolar Concentration; D019736:Prostheses and Implants; D051381:Rats; D012756:Sheep; D013552:Swine
chemical_list: D003432:Cross-Linking Reagents; D008055:Lipids; D000431:Ethanol; D003094:Collagen; D005976:Glutaral