The patient U wave.
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Computer Simulation↗
Biomedical subjects
Chantal E Conrath
Publications and source records attributed to Chantal E Conrath.
Ventricular repolarization: an overview of (patho)physiology, sympathetic effects and genetic aspects.
Most textbook knowledge on ventricular repolarization is based on animal data rather than on data from the in vivo human heart. Yet, these data have been extrapolated to the human heart, often without an appropriate caveat. Here, we review multiple aspects of repolarization, from basic membrane currents to cellular aspects including extrinsic factors such as the effects of the sympathetic nervous system. We critically discuss some mechanistic aspects of the genesis of the T-wave of the ECG in the human heart. Obviously, the T-wave results from the summation of repolarization all over the heart. The T-wave in a local electrogram ideally reflects local repolarization. The repolarization moment is composed of the moment of local activation plus local action potential duration (APD) at 90% repolarization (APD90). The duration of the latter largely depends on the balance between L-type Ca2+ current and the delayed rectifier currents. Generally speaking, there is an inverse relationship between local activation time and local APD90, leading to less dispersion in repolarization moments than in activation moments or in APD90. In transmural direction, the time needed for activation from endocardium toward epicardium has been considered to be overcompensated by shorter APD90 at the epicardium, leading to the earliest repolarization at the subepicardium. In addition, mid-myocardial cells would display the latest repolarization moments. The sparse human data available, however, do not show any transmural dispersion in repolarization moment. Also, the effect of adrenergic stimulation on APD90 has been studied mainly in animals. Again, sparse human data suggest that the effect of adrenergic stimulation is different in the human heart compared to many other mammalian hearts. Finally, aspects of the long QT syndrome are discussed, because this intrinsic genetic disease results from repolarization disorders with extrinsic aspects.
Action Potentials↗
Intercellular coupling through gap junctions masks M cells in the human heart.
OBJECTIVES: M cells have been described in many mammalian species. They are thought to be relevant for the genesis of long QT intervals, afterdepolarizations and for dispersion in action potential duration and in repolarization time. Their role in the human heart is subject to debate. METHODS: We simulated action potential propagation in a strand of transversally oriented myocytes running from endocardium towards epicardium through the left ventricular free wall. The characteristics of the myocytes were either based on the Priebe-Beuckelmann ventricular cell model or on the Luo-Rudy ventricular cell model. The former model is based on the latter and includes adaptations in order to mimic the human ventricular myocyte. The amount and location of M cells as well as the intercellular coupling through gap junctions were varied. Also, we assessed action potential duration in a Langendorff-perfused explanted human heart and in a wedge preparation obtained from such a heart. RESULTS: At low, but physiological intercellular coupling conductance, the inclusion of M cells leads to a much longer 'QT interval' in the simulations than in the in vivo or isolated human heart. Dispersion in repolarization time becomes unphysiologically large when M cells are included in the strand and is also substantially larger than in the in vivo or isolated human heart. At stronger intercellular coupling this effect disappears. CONCLUSIONS: The manifestation of M cells is absent in the human heart, probably by effective intercellular coupling, turning them functionally "invisible".
Action Potentials↗
Gender differences in the long QT syndrome: effects of beta-adrenoceptor blockade.
BACKGROUND: Gender differences have been reported in patients with the congenital long QT syndrome (LQTS). We analyzed whether electrocardiographic differences existed in females, males, girls and boys in response to beta-adrenoceptor blockade. METHODS: 12-lead ECGs before and during beta-adrenoceptor blockade were collected in 87 genotyped LQTS patients (48 women, 14 men, 12 girls and 13 boys). Up to three QTc intervals were determined in each lead of the ECG. V4 was used for QT/QTc analysis. Difference between longest and shortest QT interval was taken as a measure for dispersion of QT intervals. RESULTS: (1) Adult males had the greatest shortening of the QTc interval upon treatment with beta-adrenoceptor blockade. During treatment, adult males with LQTS(1) (mutation in the KCNQ1 gene, affecting I(Ks) current) were found to have shorter QTc intervals than adult females; this difference did not exist in LQTS(2) patients (mutation in the HERG gene, affecting I(Kr) current). (2) Female LQTS(2) patients had a 50% larger dispersion than female LQTS(1) patients both before and during treatment. (3) Adult male LQTS(1) patients constitute the only patient group with a marked decrease in QTc intervals and dispersion associated with a 100% efficacy of treatment in response to beta-adrenoceptor blockade. CONCLUSIONS: These findings indicate that, in addition to underlying differences in repolarization between men and women, cardiac electrophysiological responses to beta-adrenoceptor blockade can be modulated by gender-related factors.
Adrenergic beta-Antagonists↗
beta3-Adrenoceptors in the heart.
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Adrenergic beta-Antagonists↗