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.