Reversal of metallothionein expression is different throughout the human myocardium after prolonged left-ventricular mechanical support.
OBJECTIVE
We examined the distribution of metallothionein (MT), a stress-inducible protein, and the cardiomyocyte diameter in human hearts after left-ventricular assist device (LVAD) support.


BACKGROUND
Remodeling in end-stage heart failure is characterized by myocyte hypertrophy and alterations of several inducible proteins. LVADs used as a bridge to cardiac transplantation unload the left ventricle and may lead to a reversal of the remodeling, but little is known about the pathophysiology of this process.


METHODS
The immunoreactivity for MT and the cardiomyocyte diameter was analyzed in left-ventricular tissue specimens of 17 patients with end-stage heart failure before and after LVAD support.


RESULTS
MT positive cells were mainly located sub-endocardially in vacuolized cardiomyocytes and in small vessels throughout the myocardium. During LVAD support, MT-positive myocytes decreased in the sub-endocardial (p < 0.008) and sub-epicardial region (p < 0.003), MT-positive vessels decreased similarly (p < 0.003). Cardiomyocyte diameter decreased significantly only in the sub-endocardium (p < 0.03). Hearts of patients supported longer than 88 days (= median) showed substantially lower MT reactivity at the time of LVAD explantation as compared to patients supported less than 88 days.


CONCLUSIONS
Our results suggest that unloading of the left ventricle during prolonged LVAD support leads to regression of cellular hypertrophy and a decrease of MT expression. The preferential reduction of MT-positive vacuolized cardiomyocytes in the sub-endocardium is comparable with the concept of greatest reduction of wall stress in this area of the myocardium and may be due to the improvement of myocardial blood flow and the energy balance.
Gerhard-Domagk-Institute of Pathology, University of Muenster, Münster, Germany. baba@uni-muenster.de
H A
HA
Baba
F
F
Grabellus
C
C
August
G
G
Plenz
A
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Takeda
T D
TD
Tjan
C
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Schmid
M C
MC
Deng
D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D015415:Biomarkers; D048429:Cell Size; D005549:Foreign-Body Reaction / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D006333:Heart Failure / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D006353:Heart-Assist Devices / Q000009:adverse effects; D006801:Humans; D008668:Metallothionein / Q000276:immunology / Q000378:metabolism*; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D012720:Severity of Illness Index; D020257:Ventricular Remodeling / Q000502:physiology*
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D008668:Metallothionein