Multiple defects in intracellular calcium cycling in whole failing rat heart

J. Andrew Wasserstrom, Rohan Sharma, Sunil Kapur, James E. Kelly, Alan H. Kadish, C. William Balke, Gary L. Aistrup

Research output: Contribution to journalArticle

37 Scopus citations

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 Ca2+ cycling in left ventricular epicardial myocytes of the whole heart in an animal model of congestive heart failure (CHF). Methods and Results-Intracellular Ca2+ transients were measured using confocal microscopy in whole rat hearts from age-matched Wistar-Kyoto control rats and spontaneously hypertensive rats at ≈23 months of age. Basal Ca2+ 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 Ca2+ waves compared with very little of this activity in Wistar-Kyoto control rats. A separate population of spontaneously hypertensive rat myocytes showed Ca2+ 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 Ca2+ cycling in CHF. The defects in Ca2+ 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 Ca2+ alternans in CHF. Our results suggest that defective Ca2+ cycling could contribute both to reduced cardiac output in CHF and to the establishment of repolarization gradients, thus creating the substrate for reentrant arrhythmias.

Original languageEnglish
Pages (from-to)223-232
Number of pages10
JournalCirculation: Heart Failure
Volume2
Issue number3
DOIs
StatePublished - May 1 2009
Externally publishedYes

Keywords

  • Arrhythmia
  • Calcium
  • Heart failure
  • Sarcoplasmic reticulum

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    Wasserstrom, J. A., Sharma, R., Kapur, S., Kelly, J. E., Kadish, A. H., Balke, C. W., & Aistrup, G. L. (2009). Multiple defects in intracellular calcium cycling in whole failing rat heart. Circulation: Heart Failure, 2(3), 223-232. https://doi.org/10.1161/CIRCHEARTFAILURE.108.811539