Differential regulation of Ca2+-dependent ATPase-activity in left ventricular myocardium during mechanical circulatory support.

Abstract

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.

• Authors: Hendrik Milting, Astrid Kassner, Dietmar Böthig, Rolf Thieleczek, Harald Kögler, Nils Teucher, Helmut E Meyer, Latif Arusoglu, Kazutomo Minami, Reiner Körfer, Aly El-Banayosy
• Journal: The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation (J Heart Lung Transplant) Vol. 22 Issue 11 Pg. 1209-16 (Nov 2003) ISSN: 1053-2498 [Print] United States
• PMID: 14585382 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calcium-Transporting ATPases
• Hydroxyproline

Topics

• Adult
• Aged
• Blotting, Western
• Calcium-Transporting ATPases (metabolism)
• Child
• Heart Ventricles
• Heart-Assist Devices
• Humans
• Hydroxyproline (metabolism)
• Middle Aged
• Myocardium (enzymology, ultrastructure)
• ROC Curve
• Sarcoplasmic Reticulum (enzymology)