Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Circ Heart Fail. 2009 May;2(3):223-32. doi: 10.1161/CIRCHEARTFAILURE.108.811539. Epub 2009 Mar 30.

Multiple defects in intracellular calcium cycling in whole failing rat heart.

Author information

  • 1Departments of Medicine and Molecular Pharmacology and Biological Chemistry and the Feinberg Cardiovascular Research Institute, Northwestern University Feinberg School of Medicine, Chicago, Ill 60611, USA. ja-wasserstrom@northwestern.edu

Abstract

BACKGROUND:

A number of defects in excitation-contraction coupling have been identified in failing mammalian hearts. The goal of this study was to measure the defects in intracellular Ca(2+) cycling in left ventricular epicardial myocytes of the whole heart in an animal model of congestive heart failure (CHF).

METHODS AND RESULTS:

Intracellular Ca(2+) transients were measured using confocal microscopy in whole rat hearts from age-matched Wistar-Kyoto control rats and spontaneously hypertensive rats at approximately 23 months of age. Basal Ca(2+) transients in myocytes in spontaneously hypertensive rats were smaller in amplitude and longer in duration than Wistar-Kyoto control rats. There was also greater variability in transient characteristics associated with duration between myocytes of CHF than Wistar-Kyoto controls. Approximately 21% of CHF myocytes demonstrated spontaneous Ca(2+) waves compared with very little of this activity in Wistar-Kyoto control rats. A separate population of spontaneously hypertensive rat myocytes showed Ca(2+) waves that were triggered during pacing and were absent at rest (triggered waves). Rapid pacing protocols caused Ca(2+) alternans to develop at slower heart rates in CHF.

CONCLUSIONS:

Epicardial cells demonstrate both serious defects and greater cell-to-cell variability in Ca(2+) cycling in CHF. The defects in Ca(2+) cycling include both spontaneous and triggered waves of Ca(2+) release, which promote triggered activity. The slowing of Ca(2+) repriming in the sarcoplasmic reticulum is probably responsible for the increased vulnerability to Ca(2+) alternans in CHF. Our results suggest that defective Ca(2+) cycling could contribute both to reduced cardiac output in CHF and to the establishment of repolarization gradients, thus creating the substrate for reentrant arrhythmias.

Comment in

PMID:
19808344
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for HighWire
    Loading ...
    Write to the Help Desk