title: Towards a Tissue-Engineered Contractile Fontan-Conduit: The Fate of Cardiac Myocytes in the Subpulmonary Circulation.
abstract: The long-term outcome of patients with single ventricles improved over time, but remains poor compared to other congenital heart lesions with biventricular circulation. Main cause for this unfavourable outcome is the unphysiological hemodynamic of the Fontan circulation, such as subnormal systemic cardiac output and increased systemic-venous pressure. To overcome this limitation, we are developing the concept of a contractile extracardiac Fontan-tunnel. In this study, we evaluated the survival and structural development of a tissue-engineered conduit under in vivo conditions. Engineered heart tissue was generated from ventricular heart cells of neonatal Wistar rats, fibrinogen and thrombin. Engineered heart tissues started beating around day 8 in vitro and remained contractile in vivo throughout the experiment. After culture for 14 days constructs were implanted around the right superior vena cava of Wistar rats (n = 12). Animals were euthanized after 7, 14, 28 and 56 days postoperatively. Hematoxylin and eosin staining showed cardiomyocytes arranged in thick bundles within the engineered heart tissue-conduit. Immunostaining of sarcomeric actin, alpha-actin and connexin 43 revealed a well -developed cardiac myocyte structure. Magnetic resonance imaging (d14, n = 3) revealed no constriction or stenosis of the superior vena cava by the constructs. Engineered heart tissues survive and contract for extended periods after implantation around the superior vena cava of rats. Generation of larger constructs is warranted to evaluate functional benefits of a contractile Fontan-conduit.
authors.affiliation: Cardiac Surgery for Congenital Heart Disease, University Heart Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Biermann
authors.affiliation: Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.|DZHK (German Center for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Hamburg, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Eder
authors.affiliation: Department for Paediatric Cardiology, University Heart Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Arndt
authors.affiliation: Department for Cardiovascular Surgery, University Heart Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Hatim
authors.initials: H
authors.lastname: Seoudy
authors.affiliation: Department for Cardiovascular Surgery, University Heart Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.|DZHK (German Center for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Hamburg, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Reichenspurner
authors.affiliation: Department for Paediatric Cardiology, University Heart Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Mir
authors.affiliation: Cardiac Surgery for Congenital Heart Disease, University Heart Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Arlindo
authors.initials: A
authors.lastname: Riso
authors.affiliation: Department for Paediatric Cardiology, University Heart Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Kozlik-Feldmann
authors.affiliation: Department of Diagnostic and Interventional Radiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Kersten
authors.initials: K
authors.lastname: Peldschus
authors.affiliation: Department of Diagnostic and Interventional Radiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Kaul
authors.affiliation: Department of Diagnostic and Interventional Radiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Tillman
authors.initials: T
authors.lastname: Schuler
authors.affiliation: Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Krasemann
authors.affiliation: Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.|DZHK (German Center for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Hamburg, Germany.
authors.forename: Arne
authors.initials: A
authors.lastname: Hansen
authors.affiliation: Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.|DZHK (German Center for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Hamburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Eschenhagen
authors.affiliation: Cardiac Surgery for Congenital Heart Disease, University Heart Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Jörg S
authors.initials: JS
authors.lastname: Sachweh
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D006352:Heart Ventricles / Q000166:cytology / Q000637:transplantation; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000637:transplantation; D051381:Rats; D017208:Rats, Wistar; D023822:Tissue Engineering; D014683:Vena Cava, Superior