Document Detail


Subcellular structures and function of myocytes impaired during heart failure are restored by cardiac resynchronization therapy.
MedLine Citation:
PMID:  22253411     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
RATIONALE: Cardiac resynchronization therapy (CRT) is an established treatment for patients with chronic heart failure. However, CRT-associated structural and functional remodeling at cellular and subcellular levels is only partly understood.
OBJECTIVE: To investigate the effects of CRT on subcellular structures and protein distributions associated with excitation-contraction coupling of ventricular cardiomyocytes.
METHODS AND RESULTS: Our studies revealed remodeling of the transverse tubular system (t-system) and the spatial association of ryanodine receptor (RyR) clusters in a canine model of dyssynchronous heart failure (DHF). We did not find this remodeling in a synchronous heart failure model based on atrial tachypacing. Remodeling in DHF ranged from minor alterations in anterior left ventricular myocytes to nearly complete loss of the t-system and dissociation of RyRs from sarcolemmal structures in lateral cells. After CRT, we found a remarkable and almost complete reverse remodeling of these structures despite persistent left ventricular dysfunction. Studies of whole-cell Ca(2+) transients showed that the structural remodeling and restoration were accompanied with remodeling and restoration of Ca(2+) signaling.
CONCLUSIONS: DHF is associated with regional remodeling of the t-system. Myocytes undergo substantial structural and functional restoration after only 3 weeks of CRT. The finding suggests that t-system status can provide an early marker of the success of this therapy. The results could also guide us to an understanding of the loss and remodeling of proteins associated with the t-system. The steep relationship between free Ca(2+) and contraction suggests that some restoration of Ca(2+) release units will have a disproportionately large effect on contractility.
Authors:
Frank B Sachse; Natalia S Torres; Eleonora Savio-Galimberti; Takeshi Aiba; David A Kass; Gordon F Tomaselli; John H Bridge
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-01-17
Journal Detail:
Title:  Circulation research     Volume:  110     ISSN:  1524-4571     ISO Abbreviation:  Circ. Res.     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-02-20     Completed Date:  2012-04-09     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  588-97     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Calcium / metabolism*
Cardiac Resynchronization Therapy*
Disease Models, Animal
Dogs
Excitation Contraction Coupling*
Heart Failure / metabolism,  pathology,  physiopathology,  therapy*
Male
Membrane Potentials
Myocardial Contraction
Myocytes, Cardiac / metabolism*,  pathology
Recovery of Function
Ryanodine Receptor Calcium Release Channel / metabolism
Sarcolemma / metabolism
Time Factors
Ventricular Dysfunction, Left / metabolism,  pathology,  physiopathology,  therapy*
Ventricular Function, Left*
Ventricular Remodeling*
Grant Support
ID/Acronym/Agency:
P01 HL077180/HL/NHLBI NIH HHS; R01 HL094464/HL/NHLBI NIH HHS; R01 HL094464/HL/NHLBI NIH HHS; R01 HL094464-01A1/HL/NHLBI NIH HHS; R01 HL094464-02/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Ryanodine Receptor Calcium Release Channel; SY7Q814VUP/Calcium
Comments/Corrections

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


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