Repolarization mapping in relation to quantitative expression patterns of major ion channels in the isolated perfused healthy human heart
| Autor: | Carol Ann Remme, E. Jorge, R.F. Wiegerinck, C. Munoz, Tobias Opthof, J. Alvarez, Francisco J. Noriega, Ruben Coronel, A. Tasiam, Juan Cinca |
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| Rok vydání: | 2013 |
| Předmět: |
medicine.medical_specialty
biology business.industry KCNE2 Electrophysiology medicine.anatomical_structure Real-time polymerase chain reaction Endocrinology Ventricle Internal medicine biology.protein Cardiology Medicine Repolarization KvLQT1 Cardiology and Cardiovascular Medicine business Ion channel Whole blood |
| Zdroj: | European Heart Journal. 34:P4958-P4958 |
| ISSN: | 1522-9645 0195-668X |
| Popis: | Background: The repolarization pattern of the human heart is important for the understanding of the normal T wave and its changes in disease. This pattern is largely unknown, let alone its relation with expression patterns of ion channels. We therefore studied explanted hearts obtained from 7 donors free of structural cardiac disorders. Methods: Informed consent was obtained from the relatives of the deceased and the study was approved by the Ethical Review Board (Barcelona). Clinical data and an ECG were recorded before explantation. Hearts were perfused according to Langendorff with whole blood of the same donor. Up to 24 transmural needles (each 4 electrodes at 4 mm distance) were inserted in the left, septal and right ventricular myocardium and activation and repolarization patterns were obtained during pacing from the right atrium at a cycle length of 700 msec. Transmural tissue samples were obtained from the locations of the needles, cut in three transmural portions and immediately stored in liquid nitrogen. mRNA levels of ion channel subunits KCND2, KCND3, KCNIP2, KCNQ1, KCNE1 and KCNE2 were determined (in duplicate) by real-time quantitative PCR and normalized to the housekeeping gene HPRT. Results: From 2 hearts a complete set of electrophysiological and qPCR data were obtained. The ECG of both patients (a man of 66 and a woman of 73 years) was normal, and one had a biphasic T wave in the precordial leads. In both hearts activation-recovery intervals (ARIs) were significantly longer in the left (LV) than in the right ventricle (RV). Nevertheless, in one heart with the biphasic T wave repolarization terminated simultaneously in RV and LV. In the other heart repolarization in the RV preceded that in the LV. No relevant transmural or apico-basal gradients in repolarization were observed. However, in both hearts prominent anterior to posterior gradients were present. Of the ion channels studied, mRNA expression levels of KCND2 and KCNE2 were very low, whereas KCNIP2 was highly expressed. Coefficients of variation of the selected mRNA levels was considerably larger than that of ARIs (50 vs. 10%). KCND3 mRNA was significantly higher in LV than RV in both hearts. There were no relevant correlations between the density of any of the tested mRNAs and ARIs. Conclusion: We present the first repolarization and expression maps of the normal human heart. It shows that regional variability of expression is several folds higher than variability of ARIs. The distribution of repolarization gradients is not directly related to patterns of mRNAs encoding major ion channel subunits. |
| Databáze: | OpenAIRE |
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