We present a case of a pregnant woman with systemic lupus erythematosus (SLE) who was diagnosed with asymptomatic complete heart block (CHB) during pregnancy. To evaluate possible risks and benefits of pacemaker (PM) implantation, a multidisciplinary counselling board was held. Its recommendation was to perform PM implantation to prevent intra-uterine growth restriction from insufficient cardiac output using a fluoroscopic protective shield. The procedure was performed without complications and established permanent pacing on onwards ECG examinations. The patient subsequently gave birth to a healthy newborn. After a retrospective clinical case evaluation and review of relevant literature, a presumptive association between CHB and the primary diagnosis was proposed. Above that, pregnant women with SLE who develop hypertension are commonly treated with methyldopa, which may cause conduction abnormalities. Clinical recommendations for young female patients expecting pregnancy are lacking in this area. Careful diagnostic and treatment approaches should be used in the management of possible SLE-related complications in women of child-bearing age, focusing on preventable events.
- MeSH
- komplikace těhotenství * terapie MeSH
- lidé MeSH
- novorozenec MeSH
- retrospektivní studie MeSH
- růstová retardace plodu MeSH
- srdeční blokáda terapie komplikace MeSH
- systémový lupus erythematodes * komplikace MeSH
- těhotenství MeSH
- těhotné ženy MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
The transverse-axial tubular system (tubular system) of cardiomyocytes plays a key role in excitation-contraction coupling. To determine the area of the tubular membrane in relation to the area of the surface membrane, indirect measurements through the determination of membrane capacitances are currently used in addition to microscopic methods. Unlike existing electrophysiological methods based on an irreversible procedure (osmotic shock), the proposed new approach uses a reversible short-term intermittent increase in the electrical resistance of the extracellular medium. The resulting increase in the lumen resistance of the tubular system makes it possible to determine separate capacitances of the tubular and surface membranes. Based on the analysis of the time course of the capacitive current, computational relations were derived to quantify the elements of the electrical equivalent circuit of the measured cardiomyocyte including both capacitances. The exposition to isotonic low-conductivity sucrose solution is reversible which is the main advantage of the proposed approach allowing repetitive measurements on the same cell under control and sucrose solutions. Experiments on rat ventricular cardiomyocytes (n = 20) resulted in the surface and tubular capacitance values implying the fraction of tubular capacitance/area of 0.327 ± 0.018. We conclude that the newly proposed method provides results comparable to the data obtained by the currently used detubulation method and, in addition, by being reversible, allows repeated evaluation of surface and tubular membrane parameters on the same cell.
The variant c.926C > T (p.T309I) in KCNQ1 gene was identified in 10 putatively unrelated Czech families with long QT syndrome (LQTS). Mutation carriers (24 heterozygous individuals) were more symptomatic compared to their non-affected relatives (17 individuals). The carriers showed a mild LQTS phenotype including a longer QTc interval at rest (466 ± 24 ms vs. 418 ± 20 ms) and after exercise (508 ± 32 ms vs. 417 ± 24 ms), 4 syncopes and 2 aborted cardiac arrests. The same haplotype associated with the c.926C > T variant was identified in all probands. Using the whole cell patch clamp technique and confocal microscopy, a complete loss of channel function was revealed in the homozygous setting, caused by an impaired channel trafficking. Dominant negativity with preserved reactivity to β-adrenergic stimulation was apparent in the heterozygous setting. In simulations on a human ventricular cell model, the dysfunction resulted in delayed afterdepolarizations (DADs) and premature action potentials under β-adrenergic stimulation that could be prevented by a slight inhibition of calcium current. We conclude that the KCNQ1 variant c.926C > T is the first identified LQTS-related founder mutation in Central Europe. The dominant negative channel dysfunction may lead to DADs under β-adrenergic stimulation. Inhibition of calcium current could be possible therapeutic strategy in LQTS1 patients refractory to β-blocker therapy.
- MeSH
- beta blokátory aplikace a dávkování škodlivé účinky MeSH
- detekce genetických nosičů MeSH
- dospělí MeSH
- draslíkový kanál KCNQ1 genetika MeSH
- fenotyp MeSH
- genetická predispozice k nemoci * MeSH
- genetické asociační studie MeSH
- genotyp MeSH
- haplotypy genetika MeSH
- heterozygot MeSH
- homozygot MeSH
- lidé MeSH
- mutace genetika MeSH
- rodokmen MeSH
- syndrom dlouhého QT genetika patologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Evropa MeSH
