Transplantation of engineered heart tissue as a biological cardiac assist device for treatment of dilated cardiomyopathy
Autor: | Sergey Leontyev, Rudolf Rübsamen, Stefan Dhein, Franziska Schlegel, Martin Kostelka, Martin Nichtitz, Aida Salameh, Andreas Boldt, Ronny Schmiedel, Cathleen Spath, Friedrich-Wilhelm Mohr |
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Rok vydání: | 2013 |
Předmět: |
Cardiomyopathy
Dilated Male medicine.medical_specialty Heart Ventricles Diastole Ventricular Function Left Rats Sprague-Dawley Tissue engineering Internal medicine medicine Animals Myocytes Cardiac Doxorubicin cardiovascular diseases Matrigel Tissue Engineering business.industry Dilated cardiomyopathy medicine.disease Rats Transplantation Disease Models Animal Animals Newborn Echocardiography Heart failure cardiovascular system Cardiology Dobutamine Cardiology and Cardiovascular Medicine business medicine.drug |
Zdroj: | European Journal of Heart Failure. 15:23-35 |
ISSN: | 1879-0844 1388-9842 |
DOI: | 10.1093/eurjhf/hfs200 |
Popis: | 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/dtmax, 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/dtmax, 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. |
Databáze: | OpenAIRE |
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