AIM: The aim of this study was to characterize an alternative treatment for dilated cardiomyopathy (DCM) using a novel cardiac biological assist device created from engineered heart tissue (EHT). METHODS AND RESULTS: The EHTs were constructed in vitro from matrigel, collagen, and neonatal rat cardiomyocytes as small ring-like spontaneously contracting devices. DCM was induced in 50 rats by 6 weeks doxorubicin treatment (2.5 mg/kg/week). After 38 drug-free days, rats underwent either implantation of EHT (DCM-EHT, n = 13), which was sutured around the ventricles, or sham operation (DCM-Sham, n = 12). Eleven untreated healthy rats served as the control group. Rats were investigated using a Millar catheter for pressure-volume loop recording, and by echocardiography 30 days after operation. Thereafter, the hearts were excised and investigated functionally, histologically, and biochemically. Doxorubicin led to the development of DCM with reduced fractional shortening (FS), reduced dP/dt(max), increased systolic and diastolic LV diameters, and reduced response to dobutamine. In DCM-Sham, these changes were further enhanced, while in DCM-EHT we found improved FS, dP/dt(max), and dobutamine responsiveness. In isolated hearts, electrical multielectrode mapping revealed that EHT was electrically activated synchronously to the recipient heart. Histologically, we found increased vascularization in the EHT and the recipient heart, and EHT vessels connected to the coronary system. CONCLUSIONS: Implantation of EHT improves LV performance in rats with doxorubicin-induced DCM.
AIM: The aim of this study was to characterize an alternative treatment for dilated cardiomyopathy (DCM) using a novel cardiac biological assist device created from engineered heart tissue (EHT). METHODS AND RESULTS: The EHTs were constructed in vitro from matrigel, collagen, and neonatal rat cardiomyocytes as small ring-like spontaneously contracting devices. DCM was induced in 50 rats by 6 weeks doxorubicin treatment (2.5 mg/kg/week). After 38 drug-free days, rats underwent either implantation of EHT (DCM-EHT, n = 13), which was sutured around the ventricles, or sham operation (DCM-Sham, n = 12). Eleven untreated healthy rats served as the control group. Rats were investigated using a Millar catheter for pressure-volume loop recording, and by echocardiography 30 days after operation. Thereafter, the hearts were excised and investigated functionally, histologically, and biochemically. Doxorubicin led to the development of DCM with reduced fractional shortening (FS), reduced dP/dt(max), increased systolic and diastolic LV diameters, and reduced response to dobutamine. In DCM-Sham, these changes were further enhanced, while in DCM-EHT we found improved FS, dP/dt(max), and dobutamine responsiveness. In isolated hearts, electrical multielectrode mapping revealed that EHT was electrically activated synchronously to the recipient heart. Histologically, we found increased vascularization in the EHT and the recipient heart, and EHT vessels connected to the coronary system. CONCLUSIONS: Implantation of EHT improves LV performance in rats with doxorubicin-induced DCM.
Authors: Johannes Riegler; Malte Tiburcy; Antje Ebert; Evangeline Tzatzalos; Uwe Raaz; Oscar J Abilez; Qi Shen; Nigel G Kooreman; Evgenios Neofytou; Vincent C Chen; Mouer Wang; Tim Meyer; Philip S Tsao; Andrew J Connolly; Larry A Couture; Joseph D Gold; Wolfram H Zimmermann; Joseph C Wu Journal: Circ Res Date: 2015-08-19 Impact factor: 17.367
Authors: Jia-Ling Ruan; Nathaniel L Tulloch; Maria V Razumova; Mark Saiget; Veronica Muskheli; Lil Pabon; Hans Reinecke; Michael Regnier; Charles E Murry Journal: Circulation Date: 2016-10-13 Impact factor: 29.690
Authors: Menglin Liu; Menglong Wang; Jianfang Liu; Zhen Luo; Lei Shi; Ying Feng; Li Li; Lin Xu; Jun Wan Journal: Exp Ther Med Date: 2016-10-11 Impact factor: 2.447
Authors: Jan Trieschmann; Daniel Bettin; Moritz Haustein; Annette Köster; Marek Molcanyi; Marcel Halbach; Mira Hanna; Mariam Fouad; Konrad Brockmeier; Jürgen Hescheler; Kurt Pfannkuche; Tobias Hannes Journal: Stem Cells Int Date: 2016-01-05 Impact factor: 5.443