Cardiac activation-repolarization patterns and ion channel expression mapping in intact isolated normal human hearts

Abstract

BACKGROUND: The repolarization pattern of the human heart is unknown. OBJECTIVE: The purpose of this study was to perform a multisite analysis of the activation-repolarization patterns and mRNA expression patterns of ion channel subunits in isolated human hearts. METHODS: Hearts from 3 donors without reported cardiac disease were Langendorff perfused with the patient's own blood. A standard ECG was obtained before explantation. Up to 92 unipolar electrograms from 24 transmural needles were obtained during right atrial pacing. Local activation and repolarization times and activation-recovery intervals (ARI) were measured. The mRNA levels of subunits of the channels carrying the transient outward current and slow and rapid components of the delayed rectifier current were determined by quantitative reverse transcriptase polymerase chain reaction at up to 63 sites. RESULTS: The repolarization gradients in the 3 hearts were different and occurred along all axes without midmural late repolarization. A negative activation-repolarization relationship occurred along the epicardium, but this relationship was positive in the whole hearts. Coefficients of variation of mRNA levels (40%-80%) and of the Kv7.1 protein (alpha-subunit slow delayed rectifier channel) were larger than those of ARIs (7%-17%). The regional mRNA expression patterns were similar in the 3 hearts, unlike the ARI profiles. The expression level of individual mRNAs and of Kv7.1 did not correlate with local ARIs at the same sites. CONCLUSION: In the normal human heart, repolarization gradients encompass all axes, without late midmural repolarization. Last activated areas do not repolarize first as previously assumed. Gradients of mRNAs of single ion channel subunits and of ARIs do not correlate.