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Transplantation of engineered heart tissue as a biological cardiac assist device for treatment of dilated cardiomyopathy
Author(s) -
Leontyev Sergey,
Schlegel Franziska,
Spath Cathleen,
Schmiedel Ronny,
Nichtitz Martin,
Boldt Andreas,
Rübsamen Rudolf,
Salameh Aida,
Kostelka Martin,
Mohr FriedrichWilhelm,
Dhein Stefan
Publication year - 2013
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1093/eurjhf/hfs200
Subject(s) - medicine , dilated cardiomyopathy , dobutamine , cardiology , heart failure , heart transplantation , transplantation , cardiomyopathy , doxorubicin , diastole , chemotherapy , hemodynamics , blood pressure
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 vitr o 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 d P /d t 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, d P /d t 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.