SSc is an autoimmune disease characterized by microvascular damage, endothelial dysfunction and fibrosis of the skin and the internal organs. Cardiac manifestation in patients with SSc is one of the major organ involvements. Approximately 20% of SSc patients suffer from primary cardiovascular disease and another 20% may have secondary cardiac involvement. Although cardiac arrhythmias are mostly linked to myocardial fibrosis, atrioventricular conduction abnormalities are secondary to the fibrosis of the pulse conduction system. Despite the severe consequences of ventricular rhythm disturbances in patients with SSc, the exact role of electrocardiographic markers in the prediction of these arrhythmias has not yet been clearly elucidated. Therefore, the question is whether certain ECG parameters reflecting ventricular repolarization may help to recognize scleroderma patients with increased risk for ventricular arrhythmias and sudden cardiac death.

The high electric field across the plasma membrane might influence the conformation and behavior of transmembrane proteins that have uneven charge distributions in or near their transmembrane regions. Membrane depolarization of T cells occurs in the tumor microenvironment and in inflamed tissues because of K release from necrotic cells and hypoxia affecting the expression of K channels. However, little attention has been given to the effect of membrane potential (MP) changes on membrane receptor function. Therefore, we studied the influence of membrane de- and hyperpolarization on the biophysical properties and signaling of interleukin-2 (IL-2) and interleukin-15 (IL-15) receptors, which play important roles in T cell function. We investigated the mobility, clustering, and signaling of these receptors and major histocompatibility complex (MHC) I/II glycoproteins forming coclusters in lipid rafts of T cells. Depolarization by high K buffer or K channel blockers resulted in a decrease in the mobility of IL-2Rα and MHC glycoproteins, as shown by fluorescence correlation spectroscopy, whereas hyperpolarization by the K ionophore valinomycin increased their mobility. Contrary to this, the mobility of IL-15Rα decreased upon both de- and hyperpolarization. These changes in protein mobility are not due to an alteration of membrane fluidity, as evidenced by fluorescence anisotropy measurements. Förster resonance energy transfer measurements showed that most homo- or heteroassociations of IL-2R, IL-15R, and MHC I did not change considerably, either. MP changes modulated signaling by the two cytokines in distinct ways: depolarization caused a significant increase in the IL-2-induced phosphorylation of signal transducer and activator of transcription 5, whereas hyperpolarization evoked a decrease only in the IL-15-induced signal. Our data imply that the MP may be an important modulator of interleukin receptor signaling and dynamics. Enhanced IL-2 signaling in depolarized T cells highly expressing IL-2R may contribute to suppression of antitumor immune surveillance.

Ventricular fibrillation (VF) and sudden cardiac death (SCD) are predominantly caused by channelopathies and cardiomyopathies in youngsters and coronary heart disease in the elderly. Temporary factors, e.g., electrolyte imbalance, drug interactions, and substance abuses may play an additive role in arrhythmogenesis. Ectopic automaticity, triggered activity, and reentry mechanisms are known as important electrophysiological substrates for VF determining the antiarrhythmic therapies at the same time. Emergency need for electrical cardioversion is supported by the fact that every minute without defibrillation decreases survival rates by approximately 7%-10%. Thus, early defibrillation is an essential part of antiarrhythmic emergency management. Drug therapy has its relevance rather in the prevention of sudden cardiac death, where early recognition and treatment of the underlying disease has significant importance. Cardioprotective and antiarrhythmic effects of beta blockers in patients predisposed to sudden cardiac death were highlighted in numerous studies, hence nowadays these drugs are considered to be the cornerstones of the prevention and treatment of life-threatening ventricular arrhythmias. Nevertheless, other medical therapies have not been proven to be useful in the prevention of VF. Although amiodarone has shown positive results occasionally, this was not demonstrated to be consistent. Furthermore, the potential proarrhythmic effects of drugs may also limit their applicability. Based on these unfavorable observations we highlight the importance of arrhythmia prevention, where echocardiography, electrocardiography and laboratory testing play a significant role even in the emergency setting. In the following we provide a summary on the latest developments on cardiopulmonary resuscitation, and the evaluation and preventive treatment possibilities of patients with increased susceptibility to VF and SCD.

Voltage-gated Kv1.3 potassium channels are essential for maintaining negative membrane potential during T-cell activation. They interact with membrane-associated guanylate kinases (MAGUK-s) via their C-terminus and with TCR/CD3, leading to enrichment at the immunological synapse (IS). Molecular interactions and mobility may impact each other and the function of these proteins. We aimed to identify molecular determinants of Kv1.3 mobility, applying fluorescence correlation spectroscopy on human Jurkat T-cells expressing WT, C-terminally truncated (ΔC), and non-conducting mutants of mGFP-Kv1.3. ΔC cannot interact with MAGUK-s and is not enriched at the IS, whereas cells expressing the non-conducting mutant are depolarized. Here, we found that in standalone cells, mobility of ΔC increased relative to the WT, likely due to abrogation of interactions, whereas mobility of the non-conducting mutant decreased, similar to our previous observations on other membrane proteins in depolarized cells. At the IS formed with Raji B-cells, mobility of WT and non-conducting channels, unlike ΔC, was lower than outside the IS. The Kv1.3 variants possessing an intact C-terminus had lower mobility in standalone cells than in IS-engaged cells. This may be related to the observed segregation of F-actin into a ring-like structure at the periphery of the IS, leaving much of the cell almost void of F-actin. Upon depolarizing treatment, mobility of WT and ΔC channels decreased both in standalone and IS-engaged cells, contrary to non-conducting channels, which themselves caused depolarization. Our results support that Kv1.3 is enriched at the IS via its C-terminal region regardless of conductivity, and that depolarization decreases channel mobility.

BackgroundChest compression is a decisive element of cardio-pulmonary resuscitation (CPR). By applying a mechanical CPR device, compression interruptions can be minimised. We examined the efficiency of manual and device-assisted resuscitation as well as the effects of cardiovascular risk factors on the outcome of resuscitation.MethodsIn our retrospective, randomised 3-year study the data of adult patients suffering non-traumatic, out-of-hospital, sudden cardiac death (SCD) were analysed (n = 287). The data were retrieved by processing case reports, Utstein sheets and acute coronary syndrome sheets. We compared the data of patients undergoing manual (n = 232) and device-assisted resuscitation (LUCAS-2, n = 55). The primary endpoint was the on-site restoration of spontaneous circulation (ROSC).Results and conclusionIn 37% of the cases ROSC happened. With respect to ROSC an insignificantly more favourable tendency was demonstrated in the case of device-assisted resuscitation (p = 0.072). In the Lucas group, a higher success rate occurred even in the case of prolonged resuscitation. We found a better outcome in the Lucas group in the case of CPR started a longer time after the SCD (p < 0.05). A positive correlation was established between age and unsuccessful resuscitation (p = < 0.017; r = 0.125). An unfavourable correlation was observed between hypertension and the outcome of resuscitation (p = 0.018; r = 0.143). According to our results the presence of left ventricular hypertrophy poses 5.1-fold risk of unsuccessful CPR (CI: 4.97–5.29).Advanced age and structural heart diseases can play a role in the genesis of SCD. Importantly, left ventricular hypertrophy and hypertension negatively affect survival.

Adult growth hormone deficiency (AGHD) is considered a rare endocrine disorder involving patients with childhood-onset and adult-onset growth hormone deficiency (AoGHD) and characterized by adverse cardiometabolic risk profile. Besides traditional cardiovascular risk factors, endothelial dysfunction, low-grade inflammation, impaired adipokine profile, oxidative stress and hypovitaminosis D may also contribute to the development of premature atherosclerosis and higher cardiovascular risk in patients with AGHD. Growth hormone replacement has been proved to exert beneficial effects on several cardiovascular risk factors, but it is also apparent that hormone substitution in itself does not eliminate all cardiometabolic abnormalities associated with the disease. Novel biomarkers and diagnostic techniques discussed in this review may help to evaluate individual cardiovascular risk and identify patients with adverse cardiometabolic risk profile. In the absence of disease-specific guidelines detailing how to assess the cardiovascular status of these patients, we generally recommend close follow-up of the cardiovascular status as well as low threshold for a more detailed evaluation.

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Aim:The prolongation of T-wave-peak-to-end interval (Tpe) and arrhythmogenic index (AIX) could predict arrhythmias. Developing of ventricular arrhythmias is increased during hemodialysis (HD), but the effects of hemodiafiltration (HDF) on ventricular repolarization have not been elucidated yet.Methods: Thirty patients was investigated while they were receiving hemodiafiltration over a period of three months then the same group of patients was evaluated during treatment with hemodialysis for at least another three months. Ionic parameters, surface electrocardiograms (ECG), echocardiography, Holter ECGs were performed.Results: T-wave-peak-to-end interval and arrhythmogenic index significantly increased at the 240th minute of hemodialysis while did not change during hemodiafiltration. No malignant ventricular arrhythmias occurred, but number of ventricular premature beats was significantly higher during hemodialysis as compared to those during hemodiafiltration. Regarding hemodialysis a significant relationship was observed between the ratio of ventricular premature beats and arrhythmogenic index. Left ventricular mass index, septal-, posterior wall, inferior vena cava, left atrial diameters showed a positive correlation with T-wave-peakto-end interval only in the case of hemodialysis. A negative correlation occurred between the left ventricular ejection fraction, T-wave-peak-to-end interval and arrhythmogenic index, moreover between serum sodium and T-wave-peak-to-end interval, arrhythmogenic index during hemodialysis. Conclusions:Our results suggest that hemodialysis has unfavourable effect on the studied ECG parameters compared to hemodiafiltration.