title: Chronic cardiac resynchronization therapy and reverse ventricular remodeling in a model of nonischemic cardiomyopathy.
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.
authors: Department of Veterinary Biosciences, United States.
authors: Yoshinori
authors: Y
authors: Nishijima
authors: Arun
authors: A
authors: Sridhar
authors: Serge
authors: S
authors: Viatchenko-Karpinski
authors: Courtney
authors: C
authors: Shaw
authors: John D
authors: JD
authors: Bonagura
authors: William T
authors: WT
authors: Abraham
authors: Mandar S
authors: MS
authors: Joshi
authors: John Anthony
authors: JA
authors: Bauer
authors: Robert L
authors: RL
authors: Hamlin
authors: Sandor
authors: S
authors: Györke
authors: David S
authors: DS
authors: Feldman
authors: Cynthia A
authors: CA
authors: Carnes
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002304:Cardiac Pacing, Artificial; D009202:Cardiomyopathies / Q000503:physiopathology* / Q000628:therapy*; D002908:Chronic Disease; D017147:Defibrillators, Implantable; D004195:Disease Models, Animal; D004285:Dogs; D004452:Echocardiography; D004562:Electrocardiography; D004594:Electrophysiology; D006333:Heart Failure / Q000503:physiopathology / Q000628:therapy; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D066298:In Vitro Techniques; D032383:Myocytes, Cardiac / Q000502:physiology; D010138:Pacemaker, Artificial; D020257:Ventricular Remodeling
chemical_list: D002118:Calcium