BACKGROUND: Hypoplastic left heart syndrome (HLHS) is one of the most common severe congenital cardiac anomalies, characterized by a marked hypoplasia of left-sided structures of the heart, which is commonly accompanied by a thick layer of fibroelastic tissue, termed endocardial fibroelastosis (EFE). Because human EFE develops only in fetal or neonatal hearts, and often in association with reduced blood flow, we sought to mimic these conditions by subjecting neonatal and 2-wk-old rat hearts to variations of the heterotopically transplanted heart model with either no intracavitary or normal flow and compare endocardium with human EFE tissue. MATERIALS AND METHODS: Hearts obtained from neonatal and 2-wk-old rats were heterotopically transplanted in young adult Lewis rats in a working (loaded) or nonworking (unloaded) mode. After 2-wk survival, hearts were explanted for histologic analysis by staining for collagen, elastin, and cellular elements. These sections were compared with human EFE tissue from HLHS. RESULTS: EFE, consisting of collagen and elastin with scarce cellular and vascular components, developed only in neonatal unloaded transplanted hearts and displayed the same histopathologic findings as EFE from patients with HLHS. Loaded hearts and 2-wk-old hearts did not show these alterations. CONCLUSIONS: This animal model for EFE will serve as a tool to study the mechanisms of EFE formation, such as fluid forces, in HLHS in a systematic manner. A better understanding of the underlying cause of the EFE formation in HLHS will help to develop novel treatment strategies to better preserve growth of the hypoplastic left ventricle.
BACKGROUND:Hypoplastic left heart syndrome (HLHS) is one of the most common severe congenital cardiac anomalies, characterized by a marked hypoplasia of left-sided structures of the heart, which is commonly accompanied by a thick layer of fibroelastic tissue, termed endocardial fibroelastosis (EFE). Because humanEFE develops only in fetal or neonatal hearts, and often in association with reduced blood flow, we sought to mimic these conditions by subjecting neonatal and 2-wk-old rat hearts to variations of the heterotopically transplanted heart model with either no intracavitary or normal flow and compare endocardium with humanEFE tissue. MATERIALS AND METHODS: Hearts obtained from neonatal and 2-wk-old rats were heterotopically transplanted in young adult Lewis rats in a working (loaded) or nonworking (unloaded) mode. After 2-wk survival, hearts were explanted for histologic analysis by staining for collagen, elastin, and cellular elements. These sections were compared with humanEFE tissue from HLHS. RESULTS:EFE, consisting of collagen and elastin with scarce cellular and vascular components, developed only in neonatal unloaded transplanted hearts and displayed the same histopathologic findings as EFE from patients with HLHS. Loaded hearts and 2-wk-old hearts did not show these alterations. CONCLUSIONS: This animal model for EFE will serve as a tool to study the mechanisms of EFE formation, such as fluid forces, in HLHS in a systematic manner. A better understanding of the underlying cause of the EFE formation in HLHS will help to develop novel treatment strategies to better preserve growth of the hypoplastic left ventricle.
Authors: Pirooz Eghtesady; Erik Michelfelder; Mekibib Altaye; Edgar Ballard; Russel Hirsh; Robert H Beekman Journal: Ann Thorac Surg Date: 2007-02 Impact factor: 4.330
Authors: Doff B McElhinney; Melanie Vogel; Carol B Benson; Audrey C Marshall; Louise E Wilkins-Haug; Virginia Silva; Wayne Tworetzky Journal: Am J Cardiol Date: 2010-12-15 Impact factor: 2.778
Authors: Frances S de Man; M Louis Handoko; Joris J M van Ballegoij; Ingrid Schalij; Sylvia J P Bogaards; Pieter E Postmus; Jolanda van der Velden; Nico Westerhof; Walter J Paulus; Anton Vonk-Noordegraaf Journal: Circ Heart Fail Date: 2011-12-09 Impact factor: 8.790
Authors: Enrico Silingardi; Anna Laura Santunione; Francesco Rivasi; Bernard Gasser; Silvia Zago; Lorella Garagnani Journal: Am J Forensic Med Pathol Date: 2009-12 Impact factor: 0.921
Authors: Maria E Campian; Hein J Verberne; Maxim Hardziyenka; Kora de Bruin; Mariana Selwaness; Maurice J B van den Hoff; Jan M Ruijter; Berthe L F van Eck-Smit; Jacques M T de Bakker; Hanno L Tan Journal: J Nucl Med Date: 2009-07-17 Impact factor: 10.057
Authors: Xingbo Xu; Ingeborg Friehs; Tachi Zhong Hu; Ivan Melnychenko; Björn Tampe; Fouzi Alnour; Maria Iascone; Raghu Kalluri; Michael Zeisberg; Pedro J Del Nido; Elisabeth M Zeisberg Journal: Circ Res Date: 2015-01-13 Impact factor: 17.367
Authors: Jason C Kovacic; Stefanie Dimmeler; Richard P Harvey; Toren Finkel; Elena Aikawa; Guido Krenning; Andrew H Baker Journal: J Am Coll Cardiol Date: 2019-01-22 Impact factor: 24.094
Authors: Elizabeth S Clark; Victoria K Pepper; Cameron A Best; Ekene A Onwuka; Tai Yi; Shuhei Tara; Rachel Cianciolo; Peter Baker; Toshiharu Shinoka; Christopher K Breuer Journal: Cardiovasc Pathol Date: 2015-08-08 Impact factor: 2.185
Authors: Shogo Shimada; Christian Robles; Ben M W Illigens; Alejandra M Casar Berazaluce; Pedro J del Nido; Ingeborg Friehs Journal: Biomed Res Int Date: 2015-05-03 Impact factor: 3.411
Authors: Nicholas A Oh; Xuechong Hong; Ilias P Doulamis; Elamaran Meibalan; Teresa Peiseler; Juan Melero-Martin; Guillermo García-Cardeña; Pedro J Del Nido; Ingeborg Friehs Journal: JACC Basic Transl Sci Date: 2021-12-27