Chronic cardiac resynchronization therapy and reverse ventricular remodeling in a model of nonischemic cardiomyopathy

Yoshinori Nishijima, Arun Sridhar, Serge Viatchenko-Karpinski, Courtney Shaw, John D. Bonagura, William T. Abraham, Mandar S. Joshi, John Anthony Bauer, Robert L. Hamlin, Sandor Györke, David S. Feldman, Cynthia A. Carnes

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

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.

Original languageEnglish
Pages (from-to)1152-1159
Number of pages8
JournalLife Sciences
Volume81
Issue number14
DOIs
StatePublished - Sep 15 2007

Bibliographical note

Funding Information:
Supported in part by grants from the NIH: HL084498 (D.S.F.), HL074045 and HL063043 (S.G.)

Keywords

  • Action potential
  • Calcium
  • Cardiac resynchronization
  • Heart failure

ASJC Scopus subject areas

  • General Pharmacology, Toxicology and Pharmaceutics
  • General Biochemistry, Genetics and Molecular Biology

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