Oxidate Damage to Bioprosthetic Heart Valves – Mechanisms & Prevention”

Doctor's Name: 
Robert Levy, M.D.
The Children’s Hospital of Philadelphia, Philadelphia

Bioprosthetic heart valves (BHV), glutaraldehyde fixed heterografts (made from pig aortic valves or bovine pericardium), are used as heart valve replacements in both children and adults. These devices begin to fail after 10 years of implantation due to leaflet malfunction that is associated with either calcium deposits or primary material deterioration. The investigators will study the possibility that primary material deterioration is due to oxidative stress, defined as damage due to inflammation and the related production of oxidizing compounds that are known to damage nonliving surgical implants, such as prosthetic heart valves. A mechanistic approach will document the susceptibility of BHV to oxidative damage. A therapeutic strategy will also be studied, preventing oxidative damage through  both the chemical attachment of an anti-oxidant, 3-(4-hydroxy-3,5-di-tert-butylphenyl) propyl amine (DBP-amine) to BHV or incorporation of a manganese-porphyrin catalyst, thereby reducing the risk for oxidative destruction of BHV. These studies will investigate both chemical syntheses to create modified BHV, bench top studies, and animal implants using rats. It is hoped that the results will lead to improved prosthetic heart valves for human use, and a NIH sponsored program to investigate this subject.

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