Search Results (7)

Optical mapping, nanotechnology-based multielectrode arrays and automated patch-clamp allow transmembrane voltage mapping with high spatial resolution, as well as L-type calcium and inward rectifier currents measurements using native mammalian cardiomyocytes. However, these methods are limited to in vitro and ex vivo experiments, while magnetocardiography (MCG) might offer a novel approach for non-invasive preclinical safety assessments of new drugs in intact and even conscious rodents by reconstructing the ventricular action potential waveform (rVAPw) from MCG signals. Objective: This study aims to assess the feasibility of rVAPw reconstruction from MCG signals in Guinea pigs (GPs) and validate the results by comparison with simultaneously recorded epicardial ventricular monophasic action potentials (eVMAP). Methods: Unshielded MCG (uMCG) data of 18 GPs, investigated anaesthetized and awake at ages of 5, 14, and 26 months using a 36-channel DC-SQUID system, were analyzed to calculate rVAPw from MCG’s current arrow map. Results: Successful rVAPw reconstruction from averaged MCG showed good alignment with eVMAP waveforms. However, some rVAPw displayed incomplete or distorted repolarization at sites with lower MCG amplitude. Conclusions: 300-s uMCG averaging allowed rVAPw reconstruction in intact GPs. Occasionally distorted rVAPw suggests the need for dedicated MCG devices development, with higher density of optimized vector sensors, and modelling tailored for small animal hearts. Full article

Bioelectronic medicines record biological signals and provide electrical stimulation for the treatment of diseases. Advanced bioelectronic therapies require the development of electrodes that match the softness of the implanted tissues, as the present metal electrodes do not meet this condition. The objective of the present work was to investigate whether the electroconductive polymer polypyrrole (PPy) could be used for fabricating such electrodes, as PPy is several orders softer than metals. For this purpose, we here investigated if electrodes made using coatings and films of PPy doped with naphthalin-2-sulfonic acid (PPy/N) are capable to record and elicit by stimulation cardiac monophasic action potentials (MAPs) and if PPy/N is also biocompatible. The results of this study showed that the tested PPy/N electrodes are capable of recording MAPs almost identical to the MAPs recorded with platinum electrodes and eliciting stimulation-evoked MAPs almost identical to the spontaneous MAPs. In addition, we show here that the cell cultures that we used for biocompatibility tests grew in a similar manner on PPy/N and platinum substrates. We, therefore, conclude that PPy/N coatings and films have recording and electrical stimulation capabilities that are similar to those of platinum electrodes and that PPy/N substrates are as biocompatible as the platinum substrates. Full article

Background: Previous studies suggest a direct effect of sacubitril on cardiac electrophysiology and indicate potential arrhythmic interactions between sacubitril and antiarrhythmic drugs. Therefore, the aim of this study was to explore the electrophysiologic effects of combining sacubitril with the antiarrhythmic drugs d,l-sotalol and mexiletine in isolated hearts. Methods and results: A total of 25 rabbit hearts were perfused using a Langendorff setup. Following baseline data collection, hearts were treated with mexiletine (25 µM, 13 hearts) or d,l-sotalol (100 µM, 12 hearts). Monophasic action potential demonstrated an abbreviation of action potential duration (APD₉₀) after administration of mexiletine. Spatial dispersion of repolarization remained unchanged after mexiletine treatment, whereas effective refractory periods (ERP) were significantly prolonged. D,l-sotalol prolonged cardiac repolarization and amplified spatial dispersion. Further infusion of sacubitril (5 µM) led to a significant reduction in APD₉₀ and ERP in the mexiletine group. In the d,l-sotalol group, additional administration of sacubitril shortened cardiac repolarization duration without affecting spatial dispersion. No proarrhythmic effect was observed after mexiletine treatment as assessed by a predefined pacing protocol. Additional sacubitril treatment did not increase ventricular vulnerability. When potassium concentration was reduced, 30 episodes of torsade de pointes tachycardia occurred after d,l-sotalol treatment. Additional sacubitril treatment significantly suppressed torsade de pointes tachycardia (eight episodes) in the d,l-sotalol-group. Conclusions: In class IB- and class III-pretreated hearts, sacubitril shortened refractory periods and cardiac repolarization duration. The combination of sacubitril with the antiarrhythmic drugs d,l-sotalol and mexiletine demonstrates a safe electrophysiologic profile and sacubitril reduces the occurrence of class III-related proarrhythmia, i.e., torsade de pointes tachycardia. Full article

Facial nerve stimulation (FNS) is a potential complication which may affect the auditory performance of children with cochlear implants (CIs). We carried out an exploratory prospective observational study to investigate the effects of the electrical stimulation pattern on FNS reduction in young children with CI. Ten ears of seven prelingually deafened children with ages up to 6 years old who undergone a unilateral or bilateral CI surgery were included in this study. Electromyographic (EMG) action potentials from orbicularis oculi muscle were recorded using monopolar biphasic stimulation (ST1) and multi-mode monophasic stimulation with capacitive discharge (ST2). Presence of EMG responses, facial nerve stimulation thresholds (T-FNS) and EMG amplitudes were compared between ST1 and ST2. Intra-cochlear electrodes placement, cochlear-nerve and electrode-nerve distances were also estimated to investigate their effects on EMG responses. The use of ST2 significantly reduced the presence of intraoperative EMG responses compared to ST1. Higher stimulation levels were required to elicit FNS with ST2, with smaller amplitudes, compared to ST1. No and weak correlation was observed between cochlea-nerve and electrode-nerve distances and EMG responses, respectively. ST2 may reduce FNS in young children with CI. Differently from the electrical stimulation pattern, the cochlea-nerve and electrode-nerve distances seem to have limited effects on FNS in this population. Full article

The fungal toxin fusicoccin (FC) induces rapid cell elongation, proton extrusion and plasma membrane hyperpolarization in maize coleoptile cells. Here, these three parameters were simultaneously measured using non-abraded and non-peeled segments with the incubation medium having access to their lumen. The dose–response curve for the FC-induced growth was sigmoidal shaped with the maximum at 10⁻⁶ M over 10 h. The amplitudes of the rapid growth and proton extrusion were significantly higher for FC than those for indole-3-acetic acid (IAA). The differences between the membrane potential changes that were observed in the presence of FC and IAA relate to the permanent membrane hyperpolarization for FC and transient hyperpolarization for IAA. It was also found that the lag times of the rapid growth, proton extrusion and membrane hyperpolarization were shorter for FC compared to IAA. At 30 °C, the biphasic kinetics of the IAA-induced growth rate could be changed into a monophasic (parabolic) one, which is characteristic for FC-induced rapid growth. It has been suggested that the rates of the initial phase of the FC- and IAA-induced growth involve two common mechanisms that consist of the proton pumps and potassium channels whose contribution to the action of both effectors on the rapid growth is different. Full article

Kvβ subunits belong to the aldo-keto reductase superfamily, which plays a significant role in ion channel regulation and modulates the physiological responses. However, the role of Kvβ2 in cardiac pathophysiology was not studied, and therefore, in the present study, we hypothesized that Kvβ2 plays a significant role in cardiovascular pathophysiology by modulating the cardiac excitability and gene responses. We utilized an isoproterenol-infused mouse model to investigate the role of Kvβ2 and the cardiac function, biochemical changes, and molecular responses. The deletion of Kvβ2 attenuated the QTc (corrected QT interval) prolongation at the electrocardiographic (ECG) level after a 14-day isoproterenol infusion, whereas the QTc was significantly prolonged in the littermate wildtype group. Monophasic action potentials verified the ECG changes, suggesting that cardiac changes and responses due to isoproterenol infusion are mediated similarly at both the in vivo and ex vivo levels. Moreover, the echocardiographic function showed no further decrease in the ejection fraction in the isoproterenol-stimulated Kvβ2 knockout (KO) group, whereas the wildtype mice showed significantly decreased function. These experiments revealed that Kvβ2 plays a significant role in cardiovascular pathophysiology. Furthermore, the present study revealed SLC41a3, a major solute carrier transporter affected with a significantly decreased expression in KO vs. wildtype hearts. The electrical function showed that the decreased expression of SLC41a3 in Kvβ2 KO hearts led to decreased Mg²⁺ responses, whereas, in the wildtype hearts, Mg²⁺ caused action potential duration (APD) shortening. Based on the in vivo, ex vivo, and molecular evaluations, we identified that the deletion of Kvβ2 altered the cardiac pathophysiology mediated by SLC41a3 and altered the NAD (nicotinamide adenine dinucleotide)-dependent gene responses. Full article

The aim of this study was to investigate the effects of a combination of ranolazine with different selective inhibitors of the Na⁺/Ca²⁺-exchanger (NCX) in an established experimental model of atrial fibrillation (AF). Eighteen hearts of New Zealand white rabbits were retrogradely perfused. Atrial catheters were used to record monophasic action potentials (aPRR). Hearts were paced at three different cycle lengths. Thereby, atrial action potential durations (aAPD₉₀), atrial effective refractory periods (aERP) and atrial post-repolarization refractoriness were obtained. Isoproterenol and acetylcholine were employed to increase the occurrence of AF. Thereafter, the hearts were assigned to two groups (n = 9 each group) and additionally perfused with a combination of 10 µM ranolazine and 1 µM of the selective NCX-inhibitor ORM-10103 (group A: Rano-ORM) or 10 µM ranolazine and 1 µM of another NCX-inhibitor, SEA0400 (group B: Rano-SEA). The infusion of Iso/ACh led to a shortening of aAPD₉₀, aERP, aPRR and the occurrence of AF episodes was significantly increased. Additional perfusion with ranolazine and ORM-10103 (group A) significantly prolonged the refractory periods and aPRR and AF episodes were effectively reduced. In group B, Rano-SEA led to a slight decrease in aAPD₉₀ while aERP and aPRR were prolonged. The occurrence of AF episodes was consecutively reduced. To our knowledge, this is the first study investigating the effect of ranolazine combined with different selective NCX-inhibitors in an isolated whole-heart model of AF. Both combinations prolonged aERP and aPRR and thereby suppressed the induction of AF. Full article