PREVENTION OF CALCIFICATION OF CARDIOVASCULAR PROS

THE FAILURE OF CARDIOVASCULAR BIOPROSTHESES DUE TO CALCIFICATION IS A MAJOR CLINICAL PROBLEM. THE DERIVATIVE OF A NATURAL COMPOUND HAS BEEN SYNTHESIZED; WHEN IT REACTED WITH GLUTARALDEHYDE-PRESERVED TISSUE, IT PREVENTED CALCIFICATION IN SUBCUTANEOUS BOVINE PERICARDIUM IMPLANTED FOR 21 DAYS IN 3-WEEK OLD RATS. THE LONG-TERM EFFICACY OF THIS COMPOUND IS CURRENTLY BEING INVESTIGATED. THE OBJECTIVE OF THIS RESEARCH IS TO STUDY STRUCTURAL ANALOGS OF THIS NATURAL PRODUCT, WHICH CAN REACT WITH RESIDUAL ALDEHYDE GROUPS UNDER PHYSIOLOGICAL CONDITIONS AND PROVIDE LONG-TERM ANTICALCIFICATION OF HEART VALVES. THE SPECIFIC AIMS OF THIS PROJECT ARE: (1) SYNTHESIS OF STRUCTURAL ANALOGS OF THE NATURAL COMPOUND, (2) DETERMINATION OF OPTIMUM BINDING CONDITIONS OF THESE COMPOUNDS TO THE PORCINE HEART VALVE, AND (3) IN VIVO SUBCUTANEOUS IMPLANT STUDIES IN YOUNG RATS TO ASSESS THE EFFICACY OF THE TREATMENT. THE LONG-TERM OBJECTIVE OF THIS RESEARCH IS TO DEVELOP A REAGENT TREATMENT THAT WILL PROVIDE EXTENDED ANTICALCIFICATION PROPERTIES TO HEART VALVES AND OTHER BIO- OR POLYMER-DERIVED PROSTHESES IN HUMANS.