Document Detail


Early development of intracellular calcium cycling defects in intact hearts of spontaneously hypertensive rats.
MedLine Citation:
PMID:  20889840     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Defects in excitation-contraction coupling have been reported in failing hearts, but little is known about the relationship between these defects and the development of heart failure (HF). We compared the early changes in intracellular Ca(2+) cycling to those that underlie overt pump dysfunction and arrhythmogenesis found later in HF. Laser-scanning confocal microscopy was used to measure Ca(2+) transients in myocytes of intact hearts in Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) at different ages. Early compensatory mechanisms include a positive inotropic effect in SHRs at 7.5-9 mo compared with 6 mo. Ca(2+) transient duration increased at 9 mo in SHRs, indicating changes in Ca(2+) reuptake during decompensation. Cell-to-cell variability in Ca(2+) transient duration increased at 7.5 mo, decreased at 9 mo, and increased again at 22 mo (overt HF), indicating extensive intercellular variability in Ca(2+) transient kinetics during disease progression. Vulnerability to intercellular concordant Ca(2+) alternans increased at 9-22 mo in SHRs and was mirrored by a slowing in Ca(2+) transient restitution, suggesting that repolarization alternans and the resulting repolarization gradients might promote reentrant arrhythmias early in disease development. Intercellular discordant and subcellular Ca(2+) alternans increased as early as 7.5 mo in SHRs and may also promote arrhythmias during the compensated phase. The incidence of spontaneous and triggered Ca(2+) waves was increased in SHRs at all ages, suggesting a higher likelihood of triggered arrhythmias in SHRs compared with WKY rats well before HF develops. Thus serious and progressive defects in Ca(2+) cycling develop in SHRs long before symptoms of HF occur. Defective Ca(2+) cycling develops early and affects a small number of myocytes, and this number grows with age and causes the transition from asymptomatic to overt HF. These defects may also underlie the progressive susceptibility to Ca(2+) alternans and Ca(2+) wave activity, thus increasing the propensity for arrhythmogenesis in HF.
Authors:
Sunil Kapur; Gary L Aistrup; Rohan Sharma; James E Kelly; Rishi Arora; Jiabo Zheng; Mitra Veramasuneni; Alan H Kadish; C William Balke; J Andrew Wasserstrom
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-10-01
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  299     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-03     Completed Date:  2011-01-13     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H1843-53     Citation Subset:  IM    
Affiliation:
Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Age Factors
Aging
Animals
Arrhythmias, Cardiac / etiology*,  metabolism,  physiopathology
Calcium Signaling*
Cardiac Pacing, Artificial
Disease Models, Animal
Disease Progression
Electrophysiologic Techniques, Cardiac
Excitation Contraction Coupling
Heart Failure / etiology*,  metabolism,  physiopathology
Hypertension / complications*,  metabolism,  physiopathology
Kinetics
Male
Membrane Potentials
Microscopy, Confocal
Myocytes, Cardiac / metabolism*
Rats
Rats, Inbred SHR
Rats, Inbred WKY
Sarcoplasmic Reticulum / metabolism
Grant Support
ID/Acronym/Agency:
HL-071865/HL/NHLBI NIH HHS; HL-101196/HL/NHLBI NIH HHS; HL-68733/HL/NHLBI NIH HHS
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Moderate exercise prevents impaired Ca2+ handling in heart of CO-exposed rat: implication for sensit...
Next Document:  O2 uptake and blood pressure regulation at the onset of exercise: interaction of circadian rhythm an...