Transmural Dispersion of Repolarization in Failing and Nonfailing Human Ventricle

• Published in: Circulation research Vol. 106; no. 5; pp. 981 - 991
• Main Authors: Glukhov, Alexey V, Fedorov, Vadim V, Lou, Qing, Ravikumar, Vinod K, Kalish, Paul W, Schuessler, Richard B, Moazami, Nader, Efimov, Igor R
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Heart Association, Inc 19.03.2010; Lippincott Williams & Wilkins
• Subjects: Action Potentials; Adult; Biological and medical sciences; Cardiac Pacing, Artificial; Cardiology. Vascular system; Case-Control Studies; Connexin 43 - metabolism; Female; Fundamental and applied biological sciences. Psychology; Heart; Heart Failure - complications; Heart Failure - metabolism; Heart Failure - physiopathology; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Heart Ventricles - metabolism; Heart Ventricles - physiopathology; Humans; Immunohistochemistry; Male; Medical sciences; Middle Aged; Myocardium - metabolism; Myocardium - pathology; Tachycardia, Ventricular - etiology; Tachycardia, Ventricular - metabolism; Tachycardia, Ventricular - physiopathology; Time Factors; Ventricular Fibrillation - etiology; Ventricular Fibrillation - metabolism; Ventricular Fibrillation - physiopathology; Ventricular Remodeling; Vertebrates: cardiovascular system; Voltage-Sensitive Dye Imaging; Human; Heart failure; Repolarization; Gradient; connexin43; Cardiovascular disease; Dispersion; Connexin; Vertebrata; Mammalia; Heart disease; transmural gradient; optical mapping; Circulatory system
• DOI: 10.1161/CIRCRESAHA.109.204891
• ISSN: 0009-7330

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 gradientsubepicardial, 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 APD80477±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.