Ionic current abnormalities associated with prolonged action potentials in cardiomyocytes from diseased human right ventricles

Abstract

Objectives: This study was designed to determine whether ionic currents in right ventricular myocytes from explanted human transplant recipient hearts are related to right ventricular histopathology and function. Background: Cardiac action potential duration (APD) is prolonged in ventricular tissues/cells from patients with heart failure, but the ionic mechanisms are not well documented. Methods: Membrane currents and transmembrane action potentials in myocytes from right ventricular epicardium of explanted human hearts were recorded using whole-cell patch clamp technique. Data from cells from right ventricles with severe histologic and functional abnormalities (abnormal histology group [AH]) and from right ventricles with preserved histology and function (relatively normal histology group [RNH]) were compared. Results: We found that APD at 50% (APD 50) and 90% repolarization (APD 90) were significantly longer in AH cells than in RNH cells. Early afterdepolarizations (EADs) were observed in 20% of AH cells and none of the RNH cells. Inwardly rectifying K + current (I K1) was decreased (both inward and outward components). Both transient outward K + current K + (I to1) and slowly delayed rectifier K + current (I Ks) were down-regulated in AH cells. L-type Ca 2+ (I Ca.L was not altered in AH cells. Conclusions: I K1, I to1, and I Ks are down-regulated in AH cells of human heart failure. This down-regulation contributes to APD prolongation that favors the occurrence of arrhythmogenic EADs and suggests a link between human cardiac histopathologic/functional abnormalities and arrhythmogenic ionic remodeling. © 2004 Heart Ryhthm Society. All rigths reserved.