(Circulation. 1997;95:479-488.)
© 1997 American Heart Association, Inc.
Articles |
Prevention of Bioprosthetic Heart Valve Calcification by Ethanol Preincubation
Efficacy and Mechanisms
the Department of Pediatrics and Communicable Diseases (N.V., R.J.L.), University of Michigan Medical School, Ann Arbor; the Departments of Pathology (F.J.S.), Brigham and Women's Hospital and Harvard Medical School, Boston, Mass; Cardiovascular Surgical Research Laboratories (R.B.), University of Minnesota, Minneapolis; NHLBI (H.S.K.), Bethesda, Md; and the Department of Biological Chemistry and Macromolecular Science and Engineering and the Biophysics Research Division (R.Z.), University of Michigan Medical School, Ann Arbor.
Correspondence to Robert J. Levy, MD, University of Michigan, Department of Pediatrics and Communicable Diseases, R5014 Kresge II, Box 0576, Ann Arbor, MI 48109-0576. E-mail levy{at}umich.edu
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.
Key Words: calcium • collagen • surgery • valves
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