title: Multiple defects in intracellular calcium cycling in whole failing rat heart.
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).
  
  
  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.
authors.affiliation: Departments 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
authors.forename: J Andrew
authors.initials: JA
authors.lastname: Wasserstrom
authors.forename: Rohan
authors.initials: R
authors.lastname: Sharma
authors.forename: Sunil
authors.initials: S
authors.lastname: Kapur
authors.forename: James E
authors.initials: JE
authors.lastname: Kelly
authors.forename: Alan H
authors.initials: AH
authors.lastname: Kadish
authors.forename: C William
authors.initials: CW
authors.lastname: Balke
authors.forename: Gary L
authors.initials: GL
authors.lastname: Aistrup
mesh_terms: D000200:Action Potentials; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D020013:Calcium Signaling; D002302:Cardiac Output; D002304:Cardiac Pacing, Artificial; D006333:Heart Failure / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D006352:Heart Ventricles / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D018613:Microscopy, Confocal; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000378:metabolism*; D010496:Pericardium / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013997:Time Factors