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Abstract
Grant Number: 5R44HL059731-03 PI Name: BROCKBANK, KELVIN G. PI Email: kbrockbank@organ-recovery.com PI Title: SENIOR VICE PRESIDENT Project Title: IMPROVED ALLOGRAFT HEART VALVE PRESERVATION Abstract: DESCRIPTION (provided by applicant): Cryopreserved allogeneic human heart valves are presently the preferred aortic and pulmonary heart valve prostheses for pediatric patients, women of child-bearing age and non-drug compliant patients. Unfortunately, these valves often deteriorate in younger pediatric patients. The objective of this proposal is development of cryopreservation methods that cause less interstitial damage than methods currently employed for preservation of human heart valves. In Phase I we demonstrated significant interstitial ice in heart valves during "conventional" cryopreservation. Since Phase I we have developed relatively non-cytotoxic methods for molecular ice control resulting in either modified or elimination of ice during cryopreservation. In this Phase II proposal ice control formulations will be screened using assays of structural deterioration, calcification, ice formation, morphology and cell viability using rat or sheep heart valve-derived tissues. The best formulation will be scaled up from small volume tissues to clinical-sized specimens using sheep heart valves and validated for human heart valves. Molecular ice control methods of heart valve preservation will be compared with conventionally cryopreserved valves in an allogeneic sheep model. It is anticipated that modification or reduction of ice formation in cryopreserved valves should decrease the need for reoperation due to structural deterioration and calcification in allograft recipients.
Thesaurus Terms:
cryopreservation, cryoprotective agent, heart valve, heart valve transplantation, homologous transplantation, technology /technique development
calcification, cell population study, crystallization, cytotoxicity, water
animal tissue, electron microscopy, histopathology, human tissue, immunocytochemistry, laboratory rat, tissue /cell culture
Institution: ORGAN RECOVERY SYSTEMS, INC. 701 E BAY ST, STE 433 CHARLESTON, SC 29403 Fiscal Year: 2003 Department: Project Start: 15-JAN-1998 Project End: 31-OCT-2004 ICD: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE IRG: ZRG1
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