Cardiomyocyte death in patients with end-stage heart failure before and after support with a left ventricular assist device: low incidence of apoptosis despite ubiquitous mediators.
BACKGROUND
Left ventricular assist device (LVAD) implantation in patients with end-stage heart failure results in impressive hemodynamic improvement. The effects on myocardial apoptosis and its mediators are unknown.


METHODS
Myocardial biopsies from 17 patients at the time of LVAD implantation and after explantation, at the time of heart transplantation (HTx), were examined by terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) reaction and with antibodies against Fas ligand (FasL), Fas, tumor necrosis factor (TNF)-alpha receptor 1 (TNF-R1), TNF-alpha receptor 2 (TNF-R2), TNF-alpha, TNF-alpha-converting enzyme (TACE), poly(ADP-ribose) polymerase (PARP), poly(ADP-ribose) (PAR), caspase-3 and FLICE inhibitory protein (FLIP).


RESULTS
Apoptosis incidence was low: 0.8% (range 0% to 3%) positive cardiomyocytes nuclei before support, and 0.1% (range 0% to 0.6%) after support (p < 0.01). This was accompanied by low expression of caspase-3 and high expression of the DNA repair enzyme, PARP. Its product, PAR, increased after support. Mediators and receptors inducing apoptosis as well as FLIP were widely present before and after support.


CONCLUSIONS
Despite the abundant presence of mediators and receptors inducing apoptosis, the incidence of apoptosis itself was low before and after mechanical support. The abundant expression of FLIP may suggest an important role for this protein in the inhibition of cardiomyocyte death.
de Jonge
Nicolaas
N
Heart Lung Center, Utrecht, The Netherlands. n.dejonge@azu.nl
van Wichen
Dick F
DF
van Kuik
Joyce
J
Kirkels
Hans
H
Lahpor
Jaap R
JR
Gmelig-Meyling
Frits H J
FH
van den Tweel
Jan G
JG
de Weger
Roel A
RA
D000328:Adult; D017209:Apoptosis; D001706:Biopsy; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002303:Cardiac Output, Low / Q000473:pathology* / Q000628:therapy; D005260:Female; D016027:Heart Transplantation / Q000473:pathology; D006353:Heart-Assist Devices; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D032383:Myocytes, Cardiac; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger
D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D012333:RNA, Messenger