IKr contributes to the altered ventricular repolarization that determines long-term cardiac memory

Objective: Cardiac memory (CM) is characterized by an altered T-wave morphology, which reflects altered repolarization gradients. We hypothesized that the delayed rectifier currents, I-Kr and I-Ks, might contribute to these repolarization changes. Methods: We studied conscious, chronically instrumented dogs paced from the postero-lateral left ventricular (LV) wall at rates 5 - 10% faster than sinus rate for 3 weeks. ECGs during sinus rhythm were recorded on days 0, 7, 14 and 21 of pacing. Within 3 weeks, CM achieved steady state, hearts were excised, and epicardial and endocardial tissues and myocytes were studied. Results: In unpaced controls, action potential duration to 50% and 90% repolarization (APD) in epicardium was shorter than in endocardium (P < 0.05); in CM epicardial APD increased at CL >= 500ms, while endocardial APD was either unchanged or decreased such that the transmural gradient seen in controls diminished (P < 0.05). A transmural I-Kr gradient occurred in controls (epicardium > endocardium, P < 0.05) and was reversed in CM. No I-Ks transmural gradient was found in controls, while in CM endocardial I-Ks was greater than epicardial at greater than + 50 mV Canine ERG (cERG) mRNA and protein in epicardium > endocardium in controls (P < 0.05), and this difference was lost in CM. Expression levels of KCNQ1 and KCNE1 protein were similar in all groups. Conclusions: A transcriptionally induced change in epicardial I-Kr contributes to the altered ventricular repolarization that characterizes CM. (c) 2006 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.