Hemodynamic support by left ventricular assist devices reduces cardiomyocyte DNA content in the failing human heart.
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.


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.
Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr 55, 45147 Essen, Germany.
Jeremias
J
Wohlschlaeger
Bodo
B
Levkau
Gero
G
Brockhoff
Klaus Jürgen
KJ
Schmitz
Moritz
M
von Winterfeld
Atsushi
A
Takeda
Nobuakira
N
Takeda
Jörg
J
Stypmann
Christian
C
Vahlhaus
Christof
C
Schmid
Natalia
N
Pomjanski
Alfred
A
Böcking
Hideo Andreas
HA
Baba
D000293:Adolescent; D000328:Adult; D002452:Cell Count; D002453:Cell Cycle; D002467:Cell Nucleus / Q000648:ultrastructure; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006333:Heart Failure / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy*; D006352:Heart Ventricles / Q000503:physiopathology*; D006353:Heart-Assist Devices; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D011003:Ploidies; D012038:Regeneration; D020257:Ventricular Remodeling; D055815:Young Adult
D004247:DNA