Transmural dispersion of repolarization in failing and nonfailing human ventricle

Alexey V. Glukhov, Vadim V. Fedorov, Qing Lou, Vinod K. Ravikumar, Paul W. Kalish, Richard B. Schuessler, Nader Moazami, Igor R. Efimov

Research output: Contribution to journalArticle

220 Scopus citations

Abstract

Rationale: Transmural dispersion of repolarization has been shown to play a role in the genesis of ventricular tachycardia and fibrillation in different animal models of heart failure (HF). Heterogeneous changes of repolarization within the midmyocardial population of ventricular cells have been considered an important contributor to the HF phenotype. However, there is limited electrophysiological data from the human heart. Objective: To study electrophysiological remodeling of transmural repolarization in the failing and nonfailing human hearts. Methods and Results: We optically mapped the action potential duration (APD) in the coronary-perfused scar-free posterior-lateral left ventricular free wall wedge preparations from failing (n=5) and nonfailing (n=5) human hearts. During slow pacing (S1S1=2000 ms), in the nonfailing hearts we observed significant transmural APD gradient: subepicardial, midmyocardial, and subendocardial APD80 were 383 ±21, 455 ±20, and 494±22 ms, respectively. In 60% of nonfailing hearts (3 of 5), we found midmyocardial islands of cells that presented a distinctly long APD (537 ±40 ms) and a steep local APD gradient (27 ±7 ms/mm) compared with the neighboring myocardium. HF resulted in prolongation of APD80:477 ±22 ms, 495 ±29 ms, and 506 ±35 ms for the subepi-, mid-, and subendocardium, respectively, while reducing transmural APD80 difference from 111 ±13 to 29 ±6 ms (P<0.005) and presence of any prominent local APD gradient. In HF, immunostaining revealed a significant reduction of connexin43 expression on the subepicardium. Conclusions: We present for the first time direct experimental evidence of a transmural APD gradient in the human heart. HF results in the heterogeneous prolongation of APD, which significantly reduces the transmural and local APD gradients.

Original languageEnglish
Pages (from-to)981-991
Number of pages11
JournalCirculation research
Volume106
Issue number5
DOIs
StatePublished - Mar 19 2010

Keywords

  • Connexin43
  • Heart failure
  • Optical mapping
  • Repolarization
  • Transmural gradient

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    Glukhov, A. V., Fedorov, V. V., Lou, Q., Ravikumar, V. K., Kalish, P. W., Schuessler, R. B., Moazami, N., & Efimov, I. R. (2010). Transmural dispersion of repolarization in failing and nonfailing human ventricle. Circulation research, 106(5), 981-991. https://doi.org/10.1161/CIRCRESAHA.109.204891