Hemodynamic Support by Left Ventricular Assist Devices Reduces Cardiomyocyte DNA Content in the Failing Human Heart

Abstract

Background-Whether adult cardiomyocytes have the capacity to regenerate in response to injury and, if so, to what extent are still issues of intense debate. In human heart failure, cardiomyocytes harbor a polyploid genome. A unique opportunity to study the mechanism of polyploidization is provided through the setting of hemodynamic support by left ventricular assist devices. Hence, the cardiomyocyte DNA content, nuclear morphology, and number of nuclei per cell were assessed before and after left ventricular assist device support. Methods and Results-In 23 paired myocardial samples, cardiomyocyte ploidy was investigated by DNA image cytometry, flow cytometry, and in situ hybridization. Nuclear cross-sectional area and perimeters were measured morphometrically, and the binucleated cardiomyocytes were counted. The median of the cardiomyocyte DNA content and the number of polyploid cardiomyocytes both declined significantly from 6.79 c to 4.7 c and 40.2% to 23%, whereas a significant increase in diploid cardiomyocytes from 33.4% to 50.3% and in binucleated cardiomyocytes from 4.5% to 10% after unloading was observed. Conclusions-The decrease in polyploidy and increase in diploidy after left ventricular assist device suggest a numeric increase in diploid cardiomyocytes (eg, through cell cycle progression with completion of mitosis or by increased stem cells). The cardiac regeneration that follows may serve as a morphological correlate of the recovery observed in some patients after unloading. (Circulation. 2010;121:989-996.)

Atrial Natriuretic Peptide Locally Counteracts the Deleterious Effects of Cardiomyocyte Mineralocorticoid Receptor Activation

“…This highlighted the intercalated disks and allowed discrimination of longitudinal margins, as previously described. 17 The extent of myocardial fibrosis was determined on sequential LV sections stained with 0.1% picrosirius red. 11 LV expression of connective tissue growth factor (CTGF) protein was examined by immunohistochemistry (antibody from Abcam, Cambridge, United Kingdom).…”

Myocardial Self-Repair and Congenital Heart Disease

“…VAD are also used to reduce ventricular load with the objective of enhancing the ability of the ventricle to support a greater load, i.e., to "rest" or re-train the ventricle of patients with dilated cardiomyopathy (CMP), even restoring function to the point of enabling pump removal (Birks et al, 2011). It is conceivable that the use of VAD may increase cardiomyocyte number, and evidence of this comes from recent prospective studies of myocardial biopsies showing an increased number of diploid myocytes in end stage congestive heart failure patients supported as a bridge to transplant with LVAD (Wohlschlaeger et al, 2010). Manginas (Manginas et al, 2009) has shown that endothelial progenitor cells are also mobilized by VAD use in patients.…”

Chronische Herzinsuffizienz

“…Abb. 4a "inset") nach LVAD könnte auf Fusion präexistenter Kardiomyozyten mit proliferierten Stammzellen hinweisen [43].…”