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      Engineered heart tissue grafts improve systolic and diastolic function in infarcted rat hearts.

      Nature medicine

      Animals, Newborn, Ventricular Function, Left, Transplants, methods, Tissue Engineering, Time Factors, Systole, Rats, Wistar, Rats, pharmacology, Oxygen, physiology, Myocytes, Cardiac, cytology, Myocardium, pathology, etiology, Myocardial Infarction, Myocardial Contraction, Microscopy, Confocal, Male, Magnetic Resonance Imaging, drug effects, Isometric Contraction, Insulin, Indoles, Heart Transplantation, Heart, Fluorescent Dyes, Electric Stimulation, Echocardiography, Dose-Response Relationship, Drug, Calcium, Animals

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          Abstract

          The concept of regenerating diseased myocardium by implantation of tissue-engineered heart muscle is intriguing, but convincing evidence is lacking that heart tissues can be generated at a size and with contractile properties that would lend considerable support to failing hearts. Here we created large (thickness/diameter, 1-4 mm/15 mm), force-generating engineered heart tissue from neonatal rat heart cells. Engineered heart tissue formed thick cardiac muscle layers when implanted on myocardial infarcts in immune-suppressed rats. When evaluated 28 d later, engineered heart tissue showed undelayed electrical coupling to the native myocardium without evidence of arrhythmia induction. Moreover, engineered heart tissue prevented further dilation, induced systolic wall thickening of infarcted myocardial segments and improved fractional area shortening of infarcted hearts compared to controls (sham operation and noncontractile constructs). Thus, our study provides evidence that large contractile cardiac tissue grafts can be constructed in vitro, can survive after implantation and can support contractile function of infarcted hearts.

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          Author and article information

          Journal
          10.1038/nm1394
          16582915

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