Szabolcs Szilágyi

Two inotropes with different mechanisms of action: Contractile, PDE-inhibitory and direct myofibrillar effects of levosimendan and enoximone

We characterized the Ca2+-sensitizing and phosphodiesterase (PDE)-inhibitory potentials of levosimendan and enoximone to assess their contributions to the positive inotropic effects of these drugs. In guinea pig hearts perfused in the working-heart mode, the maximal increase in cardiac output (55%, P < 0.05) was attained at 50 nM levosimendan. The corresponding value for enoximone (36%) was significantly smaller (P < 0.05) and was observed at a higher concentration (500 nM). In permeabilized myocyte-sized preparations levosimendan evoked a maximal increase of 55.8 ± 8% (mean ± SEM) in isometric force production via Ca2+ sensitization (pCa 6.2, EC50 8.4 nM). Enoximone up to a concentration of 10 μM failed to influence the isometric force. The PDE-inhibitory effects were probed on the PDE III and PDE IV isoforms. Levosimendan proved to be a 1300-fold more potent and a 90-fold more selective PDE III inhibitor (IC50 for PDE III 1.4 nM, and IC50 for PDE IV 11 μM, selectivity factor ∼8000) than enoximone (IC50 for PDE III 1.8 μM, and IC50 for PDE IV 160 μM, selectivity factor ∼90). Hence, our data support the hypothesis that levosimendan exerts positive inotropy via a Ca2+-sensitizing mechanism, whereas enoximone does so via PDE inhibition with a limited PDE III versus PDE IV selectivity.

Protein kinase C contributes to the maintenance of contractile force in human ventricular cardiomyocytes

Prolonged Ca2+ stimulations often result in a decrease in contractile force of isolated, demembranated human ventricular cardiomyocytes, whereas intact cells are likely to be protected from this deterioration. We hypothesized that cytosolic protein kinase C (PKC) contributes to this protection. Prolonged contracture (10 min) of demembranated human cardiomyocytes at half-maximal Ca2+ resulted in a 37 ± 5% reduction of active force (p < 0.01), whereas no decrease (2 ± 3% increase) was observed in the presence of the cytosol (reconstituted myocytes). The PKC inhibitors GF 109203X and Gö 6976 (10μmol/liter) partially antagonized the cytosol-mediated protection (15 ± 5 and 9 ± 2% decrease in active force, p < 0.05). Quantitation of PKC isoform expression revealed the dominance of the Ca2+-dependent PKCα over PKCδ and PKCϵ (189 ± 31, 7 ± 3, and 7 ± 2 ng/mg protein, respectively). Ca2+ stimulations of reconstituted human cardiomyocytes resulted in the translocation of endogenous PKCα, but not PKCβ1, δ, and ϵ from the cytosol to the contractile system (PKCα association: control, 5 ± 3 arbitrary units; +Ca2+, 39 ± 8 arbitrary units; p < 0.01, EC50,Ca = 645 nmol/liter). One of the PKCα-binding proteins were identified as the thin filament regulatory protein cardiac troponin I (TnI). Finally, the Ca2+-dependent interaction between PKCα and TnI was confirmed using purified recombinant proteins (binding without Ca2+ was only 28 ± 18% of that with Ca2+). Our data suggest that PKCα translocates to the contractile system and anchors to TnI in a Ca2+-dependent manner in the human heart, contributing to the maintenance of contractile force.

Recurrent Arterial Thrombosis Associated With the Antithrombin Basel Variant and Elevated Lipoprotein(a) Plasma Level in an Adolescent Patient

Both myocardial infarction and ischemic stroke are rare in the young. Yet a 15-year-old male patient suffered a myocardial infarction and later an ischemic stroke despite uninterrupted antiplatelet therapy. His medical history involved the surgical correction of an incomplete atrioventricular canal defect at the age of 13 years. No cardiovascular risk factors other than elevated lipoprotein(a) level could be identified. His antithrombin (AT) activity was decreased and DNA sequence analysis revealed heterozygosity for AT Basel (p.Pro41Leu), a variant with impaired heparin binding. This report supports a possible additional pathophysiological role for AT Basel and elevated lipoprotein(a) level in arterial thrombogenesis.

Throughput performance analysis of the multipath communication library MPT

Although the currently used mobile communication equipments (laptops, tablets, phones) usually have many network interfaces, the Internet communication technology uses only a single communication path for a connection. In this paper we would like to introduce a new architecture, which gives an easy-to-use extension for the current TCP/IP protocol stack and offers the possibility of using multiple paths for the communication, without rewriting the applications. The new architecture was implemented in Linux by a software tool named MPT. A laboratory environment was established for the throughput performance evaluation of the MPT based multipath communication. The measurement results show that the throughput capacity of the single paths can be efficiently aggregated by MPT.

The Effects of Different Congestion Management Algorithms over Voip Performance

This paper presents one of the features of DS (Differentiated Services) architecture, namely the queuing or congestion management. Packets can be placed into separate buffer queues, on the basis of the DS value. Several forwarding policies can be used to favor high priority packets in different ways. The major reason for queuing is that the router must hold the packet in its memory while the outgoing interface is busy with sending another packet. The main goal is to compare the performance of the following queuing mechanisms using a laboratory environment: FIFO (First-In First-Out), CQ (Custom Queuing), PQ (Priority Queuing), WFQ (Weighted Fair Queuing), CBWFQ (Class Based Weighted Fair Queuing) and LLQ (Low Latency Queuing). The research is empirical and qualitative, the results are useful both in infocommunication and in education. Keywords—CBWFQ; congestion; CQ; FIFO; LLQ; Pagent; PQ; queuing; WFQ

Intracardiac echocardiography guided cardiac tumormass biopsy

Primary cardiac tumors are rare and often occur without major symptoms. The appropriate therapy for cardiac tumors without metastasis is surgical resection and chemotherapy. However, for certain patients, when the tumor cannot be safely removed, biopsy is recommended since it allows histology examination and further therapeutical considerations. The aim of our case presentation is to describe the case of a 56-year-old woman, in whom cardiac tumor-mass was revealed because of recurrent pericardial fluids. The mass appeared to be non-resectable, therefore biopsy with an eventual histological examination was planned. Intracardiac echocardiography guided percutaneous biopsy was performed. Intracardiac ultrasound ensured accurate localization of the tumor, the catheter-based grasping device and the excision could be instantly monitored. This case demonstrates that an intracardiac ultrasound-guided tumor mass biopsy is a feasible method, which increases accuracy and ensures safety.

ORM-3819 promotes cardiac contractility through Ca2+ sensitization in combination with selective PDE III inhibition, a novel approach to inotropy

This study is the first pharmacological characterization of the novel chemical entity, ORM-3819 (L-6-{4-[N-(4-Hydroxi-3-methoxy-2-nitro-benzylidene)-hydrazino]-phenyl}-5-methyl-4,5-dihydro-2H-pyridazin-3-one), focusing primarily on its cardiotonic effects. ORM-3819 binding to cardiac troponin C (cTnC) was confirmed by nuclear magnetic resonance spectroscopy, and a selective inhibition of the phosphodiesterase III (PDE III) isozyme (IC50=3.88±0.3 nM) was revealed during in vitro enzyme assays. The Ca(2+)-sensitizing effect of ORM-3819 was demonstrated in vitro in permeabilized myocyte-sized preparations from left ventricles (LV) of guinea pig hearts (ΔpCa50=0.12±0.01; EC50=2.88±0.14 µM). ORM-3819 increased the maximal rate of LV pressure development (+dP/dtmax) (EC50=8.9±1.7 nM) and LV systolic pressure (EC50=7.63±1.74 nM) in Langendorff-perfused guinea pig hearts. Intravenous administration of ORM-3819 increased LV+dP/dtmax (EC50=0.13±0.05 µM/kg) and improved the rate of LV pressure decrease (-dP/dtmax); (EC50=0.03±0.02 µM/kg) in healthy guinea pigs. In an in vivo dog model of myocardial stunning, ORM-3819 restored the depressed LV+dP/dtmax and improved % segmental shortening (%SS) in the ischemic area (to 18.8±3), which was reduced after the ischaemia-reperfusion insult (from 24.1±2.1 to 11.0±2.4). Our data demonstrate ORM-3819 as a potent positive inotropic agent exerting its cardiotonic effect by a cTnC-dependent Ca(2+)-sensitizing mechanism in combination with the selective inhibition of the PDE III isozyme. This dual mechanism of action results in the concentration-dependent augmentation of the contractile performance under control conditions and in the postischemic failing myocardium.

Multiway switching controller design using FPGA

Multiway switching has become nowadays quite frequently used in building wiring. It can be defined as an interconnection of two or more electrical switches in order to control an electrical load from more than one location. Although the electrical load is often a lamp, electrical outlets, fans, pumps, heaters or other appliances, it can also be controlled by multiway switching. However, in this paper we will deal only with lighting systems. Special switches are required to implement the system (three-way and four-way switches) that have additional contacts, and extra wires must be run between them. In this way the light can be controlled from dierent spots, e.g. the top and bottom of stairs or the end of a long hallway. Externally there is a resemblance between these switches and the standard single-pole ones. Extra connections make possible the control of a circuit from multiple locations. By connecting one or more four-way switches in-line, with three-way switches at either end, the light can be controlled from three or more locations. Toggling any switch changes the state of the light from o to on, or from on to o. We would like to introduce a solution in this paper, based on FPGA for the mentioned system and using HDL. The aim is to attain a high level of generalization by applying any (even quite large) number of switches and lights.

Idiopathiás fascicularis kamrai tachycardia ablatiója [Ablation of idiopathic fascicular ventricular tachycardia]

Idiopathic fascicular ventricular tachycardia is an important and not very rare cardiac arrhythmia with specific electrocardiographic features and therapeutic options. Ventricular tachycardia is characterized by relatively narrow QRS complex and right bundle branch block pattern. The QRS axis depends on which fascicle is involved in the re-entry. Left axis deviation is noted with left posterior fascicular tachycardia and right axis deviation with left anterior fascicular tachycardia. A left septal fascicular tachycardia with normal QRS axis is also possible. Idiopathic fascicular tachycardia is usually seen in individuals without structural heart disease. Response to verapamil is an important feature of fascicular tachycardia. In some cases intravenous adenosine may also terminate the arrhythmia. During electrophysiology study, presystolic or diastolic potentials precede the QRS, presumed to originate from the Purkinje fibers. The potentials can be recorded during sinus rhythm and ventricular tachycardia in many patients with fascicular tachycardia. This potential (so-called Purkinje potential) has been used as a guide to catheter ablation. Correct diagnosis of fascicular tachycardia is very important because catheter ablation is very effective in the treatment of this type of ventricular tachycardia. In this review, we describe three patients with idiopathic ventricular tachycardia and their successful catheter ablation, and summarize the actual knowledge of the diagnosis and management of this special ventricular tachycardia.Az idiopathias fascicularis kamrai tachycardia fontos es nem nagyon ritka szivritmuszavar specifi kus EKG-jelekkel es terapias lehetősegekkel. A kamrai tachycardia EKG-kepe relative keskeny QRS-morfologiat mutat a jobb-Tawara-szar-blokk morfologia javal. A QRS-tengelyallas attol fugg, hogy melyik fasciculus resze a reentry kornek. Baltengely-deviacio van jelen bal posterior fascicularis tachycardia, jobbtengely-deviacio bal anterior fascicularis tachycardia eseten. Bal septalis fascicularis tachycardia egyutt jarhat normalis tengelyallassal is. A fascicularis tachycardiak altalaban strukturalis szivbetegseg nelkul alakulnak ki. A fascicularis tachycardiak egyik fontos ismerve, hogy verapamilkezelesre jol reagalnak. Nehany esetben intravenas adenozin is hatekony lehet a ritmuszavar terminalasaban. A fascicularis tachycardiaban szenvedő betegek nagy reszeben sinusrhythmusban es a kamrai tachycardia alatt is a QRS-t megelőző preszisztoles vagy diasztoles potencial regisztralhato, amely feltehetően a Purkinje-rostokbol ered. Ez az ugynevezett P-potencial szolgal segitsegul a leghatekonyabb terapia, a kateterablatio soran. A ritmuszavar azonnali felismerese es megfelelő helyre tortenő iranyitasa azert fontos, mert a ritmuszavar kitűnően ablalhato, es az ablatio kurativ. Attekintesunkben harom fi atal idiopathias fascicularis tachycardiaban szenvedő betegunk kortortenetet es sikeres ablatiojat irjuk le, es az esetek kapcsan foglaljuk ossze a specialis ritmuszavarral kapcsolatos jelenlegi ismereteinket. Kulcsszavak: fascicularis tachycardia, ablatio, ritmuszavar Ablation of idiopathic fascicular ventricular tachycardia Idiopathic fascicular ventricular tachycardia is an important and not very rare cardiac arrhythmia with specifi c electrocardiographic features and therapeutic options. Ventricular tachycardia is characterized by relatively narrow QRS complex and right bundle branch block pattern. The QRS axis depends on which fascicle is involved in the re-entry. Left axis deviation is noted with left posterior fascicular tachycardia and right axis deviation with left anterior fascicular tachycardia. A left septal fascicular tachycardia with normal QRS axis is also possible. Idiopathic fascicular tachycardia is usually seen in individuals without structural heart disease. Response to verapamil is an important feature of fascicular tachycardia. In some cases intravenous adenosine may also terminate the arrhythmia. During electrophysiology study, presystolic or diastolic potentials precede the QRS, presumed to originate from the Purkinje fi bers. The potentials can be recorded during sinus rhythm and ventricular tachycardia in many patients with fascicular tachycardia. This potential (so-called Purkinje potential) has been used as a guide to catheter ablation. Correct diagnosis of fascicular tachycardia is very important because catheter ablation is very effective in the treatment of this type of ventricular tachycardia. In this review, we describe three patients with idiopathic ventricular tachycardia and their successful catheter ablation, and summarize the actual knowledge of the diagnosis and management of this special ventricular tachycardia.

Ablation of idiopathic fascicular ventricular tachycardia

Idiopathic fascicular ventricular tachycardia is an important and not very rare cardiac arrhythmia with specific electrocardiographic features and therapeutic options. Ventricular tachycardia is characterized by relatively narrow QRS complex and right bundle branch block pattern. The QRS axis depends on which fascicle is involved in the re-entry. Left axis deviation is noted with left posterior fascicular tachycardia and right axis deviation with left anterior fascicular tachycardia. A left septal fascicular tachycardia with normal QRS axis is also possible. Idiopathic fascicular tachycardia is usually seen in individuals without structural heart disease. Response to verapamil is an important feature of fascicular tachycardia. In some cases intravenous adenosine may also terminate the arrhythmia. During electrophysiology study, presystolic or diastolic potentials precede the QRS, presumed to originate from the Purkinje fibers. The potentials can be recorded during sinus rhythm and ventricular tachycardia in many patients with fascicular tachycardia. This potential (so-called Purkinje potential) has been used as a guide to catheter ablation. Correct diagnosis of fascicular tachycardia is very important because catheter ablation is very effective in the treatment of this type of ventricular tachycardia. In this review, we describe three patients with idiopathic ventricular tachycardia and their successful catheter ablation, and summarize the actual knowledge of the diagnosis and management of this special ventricular tachycardia.Az idiopathias fascicularis kamrai tachycardia fontos es nem nagyon ritka szivritmuszavar specifi kus EKG-jelekkel es terapias lehetősegekkel. A kamrai tachycardia EKG-kepe relative keskeny QRS-morfologiat mutat a jobb-Tawara-szar-blokk morfologia javal. A QRS-tengelyallas attol fugg, hogy melyik fasciculus resze a reentry kornek. Baltengely-deviacio van jelen bal posterior fascicularis tachycardia, jobbtengely-deviacio bal anterior fascicularis tachycardia eseten. Bal septalis fascicularis tachycardia egyutt jarhat normalis tengelyallassal is. A fascicularis tachycardiak altalaban strukturalis szivbetegseg nelkul alakulnak ki. A fascicularis tachycardiak egyik fontos ismerve, hogy verapamilkezelesre jol reagalnak. Nehany esetben intravenas adenozin is hatekony lehet a ritmuszavar terminalasaban. A fascicularis tachycardiaban szenvedő betegek nagy reszeben sinusrhythmusban es a kamrai tachycardia alatt is a QRS-t megelőző preszisztoles vagy diasztoles potencial regisztralhato, amely feltehetően a Purkinje-rostokbol ered. Ez az ugynevezett P-potencial szolgal segitsegul a leghatekonyabb terapia, a kateterablatio soran. A ritmuszavar azonnali felismerese es megfelelő helyre tortenő iranyitasa azert fontos, mert a ritmuszavar kitűnően ablalhato, es az ablatio kurativ. Attekintesunkben harom fi atal idiopathias fascicularis tachycardiaban szenvedő betegunk kortortenetet es sikeres ablatiojat irjuk le, es az esetek kapcsan foglaljuk ossze a specialis ritmuszavarral kapcsolatos jelenlegi ismereteinket. Kulcsszavak: fascicularis tachycardia, ablatio, ritmuszavar Ablation of idiopathic fascicular ventricular tachycardia Idiopathic fascicular ventricular tachycardia is an important and not very rare cardiac arrhythmia with specifi c electrocardiographic features and therapeutic options. Ventricular tachycardia is characterized by relatively narrow QRS complex and right bundle branch block pattern. The QRS axis depends on which fascicle is involved in the re-entry. Left axis deviation is noted with left posterior fascicular tachycardia and right axis deviation with left anterior fascicular tachycardia. A left septal fascicular tachycardia with normal QRS axis is also possible. Idiopathic fascicular tachycardia is usually seen in individuals without structural heart disease. Response to verapamil is an important feature of fascicular tachycardia. In some cases intravenous adenosine may also terminate the arrhythmia. During electrophysiology study, presystolic or diastolic potentials precede the QRS, presumed to originate from the Purkinje fi bers. The potentials can be recorded during sinus rhythm and ventricular tachycardia in many patients with fascicular tachycardia. This potential (so-called Purkinje potential) has been used as a guide to catheter ablation. Correct diagnosis of fascicular tachycardia is very important because catheter ablation is very effective in the treatment of this type of ventricular tachycardia. In this review, we describe three patients with idiopathic ventricular tachycardia and their successful catheter ablation, and summarize the actual knowledge of the diagnosis and management of this special ventricular tachycardia.