[Thrombus resection in massive left atrial dilation].
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Atrial Fibrillation↗
Biomedical subjects
Nico Reinsch
Publications and source records attributed to Nico Reinsch.
Transmural dispersion of repolarization as a key factor of arrhythmogenicity in a novel intact heart model of LQT3.
BACKGROUND: Congenital and acquired long QT syndrome (LQTS) are caused by abnormalities of ionic currents underlying ventricular repolarization. For a better understanding of the mechanisms by which functional electrical instability at the level of the whole heart leads to torsade de pointes (TdP), a novel model of LQT3 was developed and the role of transmural dispersion of repolarization for the development of proarrhythmia was evaluated. METHODS AND RESULTS: In 11 Langendorff-perfused rabbit hearts, veratridine (0.1-0.5 microM), an inhibitor of sodium channel inactivation, led to a concentration-dependent increase in QT-interval and simultaneously recorded monophasic ventricular action potentials (MAPs) (p<0.05) and thereby mimicked LQT3. Veratridine reproducibly induced early afterdepolarizations (EADs) and TdP after lowering potassium concentration. In bradycardic (AV-blocked) hearts, the increase in MAP duration showed marked regional differences. It was significantly more pronounced on the left endocardium as compared to left or right epicardium. This resulted in a significant increase in dispersion of repolarization (24% at 0.1 microM, 92% at 0.25 microM, 208% at 0.5 microM; p<0.01). Left ventricular transmural dispersion of repolarization increased significantly more than interventricular dispersion (104 to 33 ms at 0.5 microM veratridine; p<0.05). CONCLUSION: By inhibition of sodium channel inactivation, veratridine mimics LQT3 in this intact heart model. In bradycardic, hypokalemic hearts, it reproducibly induced EADs and TdP in the setting of significantly increased left ventricular transmural dispersion of repolarization. Based on these experimental data, reduction of transmural dispersion of repolarization may be considered an important target for the prevention of TdP in patients with LQT3.
Action Potentials↗
Divergent proarrhythmic potential of macrolide antibiotics despite similar QT prolongation: fast phase 3 repolarization prevents early afterdepolarizations and torsade de pointes.
Macrolide antibiotics are known to have a different proarrhythmic potential in the presence of comparable QT prolongation in the surface ECG. Because the extent of QT prolongation has been used as a surrogate marker for cardiotoxicity, we aimed to study the different electrophysiological effects of the macrolide antibiotics erythromycin, clarithromycin, and azithromycin in a previously developed experimental model of proarrhythmia. In 37 Langendorff-perfused rabbit hearts, erythromycin (150-300 microM, n = 13) clarithromycin (150-300 microM, n = 13), and azithromycin (150-300 microM, n = 11) led to similar increases in QT interval and monophasic action potential (MAP) duration. In bradycardic (atrioventricular-blocked) hearts, eight simultaneously recorded epi- and endocardial MAPs demonstrated increased dispersion of repolarization in the presence of all three antibiotics. Erythromycin and clarithromycin led to early afterdepolarizations (EADs) and torsade de pointes (TdP) after lowering of potassium concentration. In the presence of azithromycin, no EAD or TdP occurred. Erythromycin and clarithromycin changed the MAP configuration to a triangular pattern, whereas azithromycin caused a rectangular pattern of MAP prolongation. In 13 additional hearts, 150 microM azithromycin was administered after previous treatment with 300 microM erythromycin and suppressed TdP provoked by erythromycin. In conclusion, macrolide antibiotics lead to similar prolongation of repolarization but show a different proarrhythmic potential (erythromycin > clarithromycin > azithromycin). In the presence of azithromycin, neither EAD nor TdP occur. This effect may be related to a rectangular pattern of action potential prolongation, whereas erythromycin and clarithromycin cause triangular action potential prolongation and induce TdP.
Animals↗