Incidental finding of a giant intracardiac angioma infiltrating both ventricles in a 35-year-old woman: a case report.

BACKGROUND: Primary cardiac tumors are rare and often asymptomatic or present with unspecific symptoms. Benign cardiac tumors of vascular origin are especially rare, with only few existing data in the literature. CASE PRESENTATION: A 35-year-old Caucasian female patient presented to our department with an asymptomatic giant intracardiac angioma infiltrating both ventricles. Evaluation of this tumor involved electrocardiography, echocardiography, cardiac magnetic resonance imaging, coronary angiography, an open myocardial biopsy, and histological examination of the resected specimen. Because our patient was asymptomatic, she was managed conservatively with regular follow-up. We discuss the treatment options available in comparison with similar cases. CONCLUSION: Diagnosis and therapy of benign cardiac tumors, especially of asymptomatic lesions, can be a challenge. There is no evidence available to help in the management of such patients. An extensive evaluation is needed with different imaging modalities, and case-specific decisions should be made that involve experts in cardiology, cardio-oncology, and heart surgery.

Mechanisms of zolpidem-induced long QT syndrome: acute inhibition of recombinant hERG K(+) channels and action potential prolongation in human cardiomyocytes derived from induced pluripotent stem cells.

BACKGROUND AND PURPOSE: Zolpidem, a short-acting hypnotic drug prescribed to treat insomnia, has been clinically associated with acquired long QT syndrome (LQTS) and torsade de pointes (TdP) tachyarrhythmia. LQTS is primarily attributed to reduction of cardiac human ether-a-go-go-related gene (hERG)/I(Kr) currents. We hypothesized that zolpidem prolongs the cardiac action potential through inhibition of hERG K(+) channels. EXPERIMENTAL APPROACH: Two-electrode voltage clamp and whole-cell patch clamp electrophysiology was used to record hERG currents from Xenopus oocytes and from HEK 293 cells. In addition, hERG protein trafficking was evaluated in HEK 293 cells by Western blot analysis, and action potential duration (APD) was assessed in human-induced pluripotent stem cell (hiPSC)-derived cardiomyocytes. KEY RESULTS: Zolpidem caused acute hERG channel blockade in oocytes (IC(50) = 61.5 µM) and in HEK 293 cells (IC(50) = 65.5 µM). Mutation of residues Y652 and F656 attenuated hERG inhibition, suggesting drug binding to a receptor site inside the channel pore. Channels were blocked in open and inactivated states in a voltage- and frequency-independent manner. Zolpidem accelerated hERG channel inactivation but did not affect I-V relationships of steady-state activation and inactivation. In contrast to the majority of hERG inhibitors, hERG cell surface trafficking was not impaired by zolpidem. Finally, acute zolpidem exposure resulted in APD prolongation in hiPSC-derived cardiomyocytes. CONCLUSIONS AND IMPLICATIONS: Zolpidem inhibits cardiac hERG K(+) channels. Despite a relatively low affinity of zolpidem to hERG channels, APD prolongation may lead to acquired LQTS and TdP in cases of reduced repolarization reserve or zolpidem overdose.

Regulation of apoptosis in HL-1 cardiomyocytes by phosphorylation of the receptor tyrosine kinase EphA2 and protection by lithocholic acid.

BACKGROUND AND PURPOSE: Heart failure and atrial fibrillation are associated with apoptosis of cardiomyocytes, suggesting common abnormalities in pro-apoptotic cardiac molecules. Activation of the receptor tyrosine kinase EphA2 causes apoptosis in vitro, and dysregulation of EphA2-dependent signalling is implicated in LEOPARD and Noonan syndromes associated with cardiomyopathy. Molecular pathways and regulation of EphA2 signalling in the heart are poorly understood. Here we elucidated the pathways of EphA2-dependent apoptosis and evaluated a therapeutic strategy to prevent EphA2 activation and cardiac cell death. EXPERIMENTAL APPROACH: EphA2 signalling was studied in an established model of doxazosin-induced apoptosis in HL-1 cells. Apoptosis was measured with TUNEL assays and as cell viability using a formazan method. Western blotting and siRNA for EphA2 were also used. KEY RESULTS: Apoptosis induced by doxazosin (EC(50) = 17.3 µM) was associated with EphA2 activation through enhanced phosphorylation (2.2-fold). Activation of pro-apoptotic downstream factors, phospho-SHP-2 (3.9-fold), phospho-p38 MAPK (2.3-fold) and GADD153 (1.6-fold) resulted in cleavage of caspase 3. Furthermore, two anti-apoptotic enzymes were suppressed (focal adhesion kinase, by 41%; phospho-Akt, by 78%). Inactivation of EphA2 with appropriate siRNA mimicked pro-apoptotic effects of doxazosin. Finally, administration of lithocholic acid (LCA) protected against apoptosis by increasing EphA2 protein levels and decreasing EphA2 phosphorylation. CONCLUSIONS AND IMPLICATIONS: EphA2 phosphorylation and activation of SHP-2 are critical steps in apoptosis. Reduction of EphA2 phosphorylation by LCA may represent a novel approach for future anti-apoptotic treatment of heart failure and atrial fibrillation.

[Cardiac two-pore-domain potassium channels (K2P): Physiology, pharmacology, and therapeutic potential]. / Kardiale Zwei-Porendomänen-Kaliumkanäle (K2P): Physiologie, Pharmakologie und therapeutisches Potenzial.

Uncontrolled electrical activity caused by ion channel dysfunction produces arrhythmia in the heart. Despite recent advances in pharmaceutical research and development, effective and safe pharmacological management of cardiac arrhythmia still remains an unmet medical need. The emerging family of two-pore-domain potassium (K2P) channels stabilizes the resting membrane potential and facilitates action potential repolarization. In the heart, genetic inactivation or inhibition of two-pore-domain K + (K2P) currents by class III antiarrhythmic drugs results in action potential prolongation. In particular, human K2P3.1 channels are selectively expressed in the atria and represent targets for the pharmacological management of atrial fibrillation. Furthermore, stretch-sensitive K2P2.1 channels are implicated in mechanoelectrical feedback and arrhythmogenesis. The current knowledge on function, regulation, and cardiac significance of K2P channels is summarized in this work, and potential therapeutic implications are highlighted.

Generation and characterization of dihydroxycarbene, HO-C-OH, by neutralization/reionization mass spectrometry.

Dihydroxycarbene is produced in the gas phase by neutralization of the HO-C-OH+. radical cation which is formed by dissociative electron ionization of oxalic acid. Reionization approximately 0.3 microseconds later shows that HO-C-OH can survive intact and, thus, exists as a stable species with appreciable barriers for dissociation or rearrangement to formic acid (HCOOH). Within the time scale of the experiment, a small fraction of the carbene decomposes to H2O+CO. Comparison of the experimental results with ab initio theory shows that the dissociating HO-C-OH molecules are generated in the electronically excited triplet state, while the large amount of surviving carbene molecules is formed in the singlet ground state.