While cardiac resynchronization therapy (CRT) has been shown to reduce
morbidity and mortality in heart failure (HF) patients, the fundamental
mechanisms for the efficacy of CRT are poorly understood. The lack
of understanding of these basic mechanisms represents a significant
barrier to our understanding of the pathogenesis of HF and potential
recovery mechanisms. Our purpose was to determine cellular mechanisms
for the observed improvement in chronic HF after CRT. We used a canine
model of chronic nonischemic cardiomyopathy. After 15 months, dogs
were randomized to continued RV tachypacing (untreated HF) or CRT
for an additional 9 months. Six minute walk tests, echocardiograms,
and electrocardiograms were done to assess the functional response
to therapy. Left ventricular (LV) midmyocardial myocytes were isolated
to study electrophysiology and intracellular calcium regulation.
Compared to untreated HF, CRT improved HF-induced increases in LV
volumes, diameters and mass (p<0.05). CRT reversed HF-induced prolongations
in LV myocyte repolarization (p<0.05) and normalized HF-induced depolarization
(p<0.03) of the resting membrane potential. CRT improved HF-induced
reductions in calcium (p<0.05). CRT did not attenuate the HF-induced
increases in LV interstitial fibrosis. Using a translational approach
in a chronic HF model, CRT significantly improved LV structure; this
was accompanied by improved LV myocyte electrophysiology and calcium
regulation. The beneficial effects of CRT may be attributable, in
part, to improved LV myocyte function.
%0 Journal Article
%1 Nish_2007_1152
%A Nishijima, Yoshinori
%A Sridhar, Arun
%A Viatchenko-Karpinski, Serge
%A Shaw, Courtney
%A Bonagura, John D
%A Abraham, William T
%A Joshi, Mandar S
%A Bauer, John Anthony
%A Hamlin, Robert L
%A Gy�rke, Sandor
%A Feldman, David S
%A Carnes, Cynthia A
%D 2007
%J Life Sci
%K Animal; Animals; Artificial; Calcium, Cardiac Cardiac, Cardiomyopathies, Chronic Defibrillators, Disease Disease; Dogs; Echocardiography; Electrocardiography; Electrophysiology; Failure, Heart Implantable; Models, Myocytes, Pacemaker, Pacing, Remodeling Ventricles, Ventricular metabolism/pathology; metabolism; physiology; physiopathology/therapy;
%N 14
%P 1152--1159
%R 10.1016/j.lfs.2007.08.022
%T Chronic cardiac resynchronization therapy and reverse ventricular
remodeling in a model of nonischemic cardiomyopathy.
%U http://dx.doi.org/10.1016/j.lfs.2007.08.022
%V 81
%X While cardiac resynchronization therapy (CRT) has been shown to reduce
morbidity and mortality in heart failure (HF) patients, the fundamental
mechanisms for the efficacy of CRT are poorly understood. The lack
of understanding of these basic mechanisms represents a significant
barrier to our understanding of the pathogenesis of HF and potential
recovery mechanisms. Our purpose was to determine cellular mechanisms
for the observed improvement in chronic HF after CRT. We used a canine
model of chronic nonischemic cardiomyopathy. After 15 months, dogs
were randomized to continued RV tachypacing (untreated HF) or CRT
for an additional 9 months. Six minute walk tests, echocardiograms,
and electrocardiograms were done to assess the functional response
to therapy. Left ventricular (LV) midmyocardial myocytes were isolated
to study electrophysiology and intracellular calcium regulation.
Compared to untreated HF, CRT improved HF-induced increases in LV
volumes, diameters and mass (p<0.05). CRT reversed HF-induced prolongations
in LV myocyte repolarization (p<0.05) and normalized HF-induced depolarization
(p<0.03) of the resting membrane potential. CRT improved HF-induced
reductions in calcium (p<0.05). CRT did not attenuate the HF-induced
increases in LV interstitial fibrosis. Using a translational approach
in a chronic HF model, CRT significantly improved LV structure; this
was accompanied by improved LV myocyte electrophysiology and calcium
regulation. The beneficial effects of CRT may be attributable, in
part, to improved LV myocyte function.
@article{Nish_2007_1152,
abstract = {While cardiac resynchronization therapy (CRT) has been shown to reduce
morbidity and mortality in heart failure (HF) patients, the fundamental
mechanisms for the efficacy of CRT are poorly understood. The lack
of understanding of these basic mechanisms represents a significant
barrier to our understanding of the pathogenesis of HF and potential
recovery mechanisms. Our purpose was to determine cellular mechanisms
for the observed improvement in chronic HF after CRT. We used a canine
model of chronic nonischemic cardiomyopathy. After 15 months, dogs
were randomized to continued RV tachypacing (untreated HF) or CRT
for an additional 9 months. Six minute walk tests, echocardiograms,
and electrocardiograms were done to assess the functional response
to therapy. Left ventricular (LV) midmyocardial myocytes were isolated
to study electrophysiology and intracellular calcium regulation.
Compared to untreated HF, CRT improved HF-induced increases in LV
volumes, diameters and mass (p<0.05). CRT reversed HF-induced prolongations
in LV myocyte repolarization (p<0.05) and normalized HF-induced depolarization
(p<0.03) of the resting membrane potential. CRT improved HF-induced
reductions in calcium (p<0.05). CRT did not attenuate the HF-induced
increases in LV interstitial fibrosis. Using a translational approach
in a chronic HF model, CRT significantly improved LV structure; this
was accompanied by improved LV myocyte electrophysiology and calcium
regulation. The beneficial effects of CRT may be attributable, in
part, to improved LV myocyte function.},
added-at = {2009-06-03T11:20:58.000+0200},
author = {Nishijima, Yoshinori and Sridhar, Arun and Viatchenko-Karpinski, Serge and Shaw, Courtney and Bonagura, John D and Abraham, William T and Joshi, Mandar S and Bauer, John Anthony and Hamlin, Robert L and Gy�rke, Sandor and Feldman, David S and Carnes, Cynthia A},
biburl = {https://www.bibsonomy.org/bibtex/2a20fb78b022916564d898b78567b3e83/hake},
description = {The whole bibliography file I use.},
doi = {10.1016/j.lfs.2007.08.022},
institution = {Department of Veterinary Biosciences, United States.},
interhash = {6e1315de15fd45809b34475c303044fe},
intrahash = {a20fb78b022916564d898b78567b3e83},
journal = {Life Sci},
keywords = {Animal; Animals; Artificial; Calcium, Cardiac Cardiac, Cardiomyopathies, Chronic Defibrillators, Disease Disease; Dogs; Echocardiography; Electrocardiography; Electrophysiology; Failure, Heart Implantable; Models, Myocytes, Pacemaker, Pacing, Remodeling Ventricles, Ventricular metabolism/pathology; metabolism; physiology; physiopathology/therapy;},
month = Sep,
number = 14,
pages = {1152--1159},
pii = {S0024-3205(07)00591-7},
pmid = {17884106},
timestamp = {2009-06-03T11:21:24.000+0200},
title = {Chronic cardiac resynchronization therapy and reverse ventricular
remodeling in a model of nonischemic cardiomyopathy.},
url = {http://dx.doi.org/10.1016/j.lfs.2007.08.022},
volume = 81,
year = 2007
}