Differential regulation of Ca2+-dependent ATPase-activity in left ventricular myocardium during mechanical circulatory support.
BACKGROUND
Myocardial recovery is observed in some end-stage heart failure patients after mechanical circulatory support. The sarcoplasmic reticulum Ca(2+)-adenosine triphosphatase (Ca2+-ATPase) activity is down-regulated in failing myocardium and contributes to heart failure-associated contraction/relaxation abnormalities. Regulation of Ca(2+)-ATPase after mechanical support was shown to be heterogeneous. Thus, we analyzed Ca(2+)-ATPase activity and protein expression in the paired myocardial samples of 21 patients supported by ventricular assist devices to identify factors that influence restoration of the Ca(2+)-transient after ventricular assist device support.


METHODS
We measured Ca(2+)-ATPase activity using a reduced nicotinamide-adenine dinucleotide-coupled reaction, determined sarcoplasmic reticulum Ca(2+)-dependent ATPase protein using Western blotting, and determined 4-hydroxyproline using amino-acid analysis.


RESULTS
The mean Ca(2+)-ATPase activity decreased at assist-device implantation and slightly increased at transplantation, but remained significantly lower than in non-failing donor hearts. However, individual responses were heterogeneous. Patients with older age, increased left ventricular diameter, and increased 4-hydroxyproline content showed down-regulation of Ca(2+)-ATPase activity, whereas we found up-regulation in patients with low values for these parameters after assist-device support.


CONCLUSIONS
Sarcoplasmic reticulum Ca(2+)-ATPase activity, which influences the myocardial Ca(2+)-transient, generally is not restored to normal values in assist-device-supported hearts, but depends on a combined score of the left ventricular end-diastolic diameter, degree of ventricular fibrosis, and age of the patient at the time of assist-device implantation.
Milting
Hendrik
H
Ruhr-Universität Bochum, Herz- und Diabeteszentrum NRW, Forschungslabor der Herzchirurgie, Bad Oeynhausen, Germany.
Kassner
Astrid
A
Böthig
Dietmar
D
Thieleczek
Rolf
R
Kögler
Harald
H
Teucher
Nils
N
Meyer
Helmut E
HE
Arusoglu
Latif
L
Minami
Kazutomo
K
Körfer
Reiner
R
El-Banayosy
Aly
A
D000328:Adult; D000368:Aged; D015153:Blotting, Western; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D002648:Child; D006352:Heart Ventricles; D006353:Heart-Assist Devices; D006801:Humans; D006909:Hydroxyproline / Q000378:metabolism; D008875:Middle Aged; D009206:Myocardium / Q000201:enzymology* / Q000648:ultrastructure; D012372:ROC Curve; D012519:Sarcoplasmic Reticulum / Q000201:enzymology
D000252:Calcium-Transporting ATPases; D006909:Hydroxyproline