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Papers by Peter Musil

European Journal of Heart Failure, Jan 28, 2009

The role of nitric oxide (NO) in heart failure (HF) is complex and remains controversial. We test... more The role of nitric oxide (NO) in heart failure (HF) is complex and remains controversial. We tested the hypothesis that the role of NO in isolated atria and cardiomyocytes is altered in isoproterenol-induced HF. Methods and results Rats received isoproterenol (ISO, 5 mg/kg/day, intraperitoneally) or vehicle for 1 week. Haemodynamic parameters were obtained by left ventricular catheterization. Effects of NOS inhibition on isolated atria and on electrically paced left ventricular myocytes were determined. Additionally, expressions of nitric oxide synthases and their allosteric modulators hsp90, caveolin-1, and caveolin-3 proteins in the left ventricles were measured. ISO increased left ventricular mass by 33% and decreased indices of left ventricular systolic and diastolic function dp/dt min and dp/dt max (both P , 0.05). Isolated atria from HF rats had a lower spontaneous beating rate (P , 0.05). NOS inhibition by L-NAME increased basal frequency and attenuated the positive chronotropic effect of beta-adrenergic stimulation in the HF group (P , 0.05). Ventricular myocytes from failing hearts had impaired cell shortening. L-NAME decreased contractility of control, but not failing myocytes. Left ventricular expressions of eNOS, hsp90, iNOS, but not nNOS or caveolins, were increased. Conclusion Despite the increased capacity for NO synthesis in isoproterenol-induced HF, NO does not sustain contractility of failing myocytes. NO may contribute to the decreased basal heart rate and it may accelerate beta-adrenergic stimulation of chronotropy.

This paper reports the development and characterisation of an assembly technology for a polymer l... more This paper reports the development and characterisation of an assembly technology for a polymer lab-on-chip. The system consists of a 150 µm deep hot embossed microfluidic channel in polycarbonate and Au electrodes fabricated separately by photolithography on polyethylenenaphthalate. The system is designed for impedimetric immunoassay detection in whole blood. Electrode layer and microfluidic substrate are joined by means of a 50 µm thick double-sided medical grade adhesive tape, adjusted with an optical alignment system. The bond proved to be liquid tight at room temperature. An alignment accuracy of 34 µm (+/-19 µm) evaluated over a set of 23 samples, was achieved. The effect of alignment accuracy of the intermediate adhesive film on whole blood flow properties in the device is studied. Already an alignment error of 70 µm increases the flushing out time of whole blood by approximately 20 %.

Global heart, Dec 1, 2018

all-cause mortality were calculated. Mortality was assessed over a median period of 47 months (ra... more all-cause mortality were calculated. Mortality was assessed over a median period of 47 months (range 21-78). Data were analyzed using descriptive statistics. Results: Anemic patients died more often within 30 days and during the observation period than non-anemic patients [223 (13.3%) anemic patients died within 30 days compared to 202 (5.2%) non-anemic patients] and [714 (42.5%) anemic patients died during the observation period compared to 751 (19.3%) non-anemic patients]. Women presented with anemia more often than men (37.5% vs. 26.8%; p<0.0001). Both the 30-day and long-term mortality were higher in non-anemic women than nonanemic men [79 (7.3%) women died within 30 days compared to 123 (4.4%) men; p <0.0001] and [270 (25.0%) women died during the observation period compared to 481 (17.1%) men; p <0.0001. On the contrary, the 30-day and long-term mortality were similar in anemic patients of both sexes [89 (13.7%) women died within 30 days compared to 134 (13.0%) men; p ¼0.66] and [274 (42.3%) women died during the observation compared to 440 (42.7%) men; p ¼0.88]. Anemia on admission predicted both a higher 30-day mortality and longterm mortality in the total patient cohort and in both sexes. Conclusion: Anemia has a similar deleterious impact on both the 30-day and long-term survival in patients with myocardial infarction undergoing PCI in both sexes. Whether anemia in MI should be treated, remains to be answered.

Bratislavské lekárske listy, 2021

AIM: Asymptomatic atrial fi brillation (AF) detection and pulmonary veins isolation (PVI) outcome... more AIM: Asymptomatic atrial fi brillation (AF) detection and pulmonary veins isolation (PVI) outcome prediction remain challenging. Our aim was to study the association between apelin and paroxysmal AF in patients undergoing radiofrequency catheter PVI. METHODS: Sixty-three consecutive patients (55 ± 8years, 12 females) with paroxysmal AF without a structural heart disease and implanted ECG loop recorders undergoing PVI and healthy control group of 34 persons (41 ± 9.5years, 21 females) were included. Apelin plasmatic concentrations were measured before and three months after PVI. AF burden was continually assessed for three years. RESULTS: Apelin was signifi cantly decreased in AF patients compared to the healthy controls (0.79 ± 0.09 vs 0.98 ± 0.06 ng/ml; p < 0.00001). Apelin plasmatic concentration of 0.89 ng/ml had 94 % specifi city and 89 % sensitivity for AF prediction with the area under the curve (AUC) of 0.96. After propensity matching to sex, age and comorbidities, apelin concentration was signifi cantly lower in AF group (0.78 ± 0.1 vs 0.99 ± 0.06 ng/ml; p < 0.0001; AUC: 0.97). There was a signifi cant inverse correlation between apelin concentration and AF burden both before and after PVI (Rho =-0.22; p = 0.05) and (Rho =-0.51; p = 0.006), respecti vely. There was no signifi cant association between pre-PVI apelin and PVI long-term outcome. CONCLUSION: In patients without a structural heart disease apelin showed a signifi cant specifi city and sensitivity for AF prediction and inversely correlated with AF burden (Tab.

Canadian Journal of Physiology and Pharmacology, Nov 1, 2016

Key morphological discoveries in recent years have included the discovery of new cell populations... more Key morphological discoveries in recent years have included the discovery of new cell populations inside the heart called cardiac telocytes. These newly described cells of the connective tissue have extremely long cytoplasmic processes through which they form functionally connected three-dimensional networks that connect cells of the immune system, nerve fibers, cardiac stem cells, and cardiac muscle cells. Based on their functions, telocytes are also referred to as "connecting cells" or "nurse cells" for cardiac progenitor stem cells. In this critical review, we provide a summary of the latest research on cardiac telocytes localized in all layers of the heart-from the historical background of their discovery, through ultrastructural, immunohistochemical, and functional characterizations, to the application of this knowledge to the fields of cardiology, stem cell research, and regenerative medicine.

International Journal of Molecular Sciences, Oct 5, 2016

Systematic physical activity increases physical fitness and exercise capacity that lead to the im... more Systematic physical activity increases physical fitness and exercise capacity that lead to the improvement of health status and athletic performance. Considerable effort is devoted to identifying new biomarkers capable of evaluating exercise performance capacity and progress in training, early detection of overtraining, and monitoring health-related adaptation changes. Recent advances in OMICS technologies have opened new opportunities in the detection of genetic, epigenetic and transcriptomic biomarkers. Very promising are mainly small non-coding microRNAs (miRNAs). miRNAs post-transcriptionally regulate gene expression by binding to mRNA and causing its degradation or inhibiting translation. A growing body of evidence suggests that miRNAs affect many processes and play a crucial role not only in cell differentiation, proliferation and apoptosis, but also affect extracellular matrix composition and maintaining processes of homeostasis. A number of studies have shown changes in distribution profiles of circulating miRNAs (c-miRNAs) associated with various diseases and disorders as well as in samples taken under physiological conditions such as pregnancy or physical exercise. This overview aims to summarize the current knowledge related to the response of blood c-miRNAs profiles to different modes of exercise and to highlight their potential application as a novel class of biomarkers of physical performance capacity and training adaptation.

Bratislavské lekárske listy, 2020

BACKGROUND: Previous studies showed an association between apelin and atrial fi brillation (AF). ... more BACKGROUND: Previous studies showed an association between apelin and atrial fi brillation (AF). The aim of this study was to analyse the effect of pulmonary vein isolation (PVI) in patients with paroxysmal AF on plasmatic apelin concentrations. METHODS: Nine consecutive patients (aged from 43 to 69 years, 3 females and 6 males) with documented paroxysmal atrial fi brillation and implanted loop recorders (ILR) for continuous ECG monitoring were included in this study. All the patients underwent a radiofrequency catheter ablation with PVI. RESULTS: The plasmatic concentration of apelin increased after PVI. The average plasmatic concentration of apelin before PVI was 0.299 ng/ml (±0.16), 3 months after PVI 0.462 ng/ml (± 0.10) and 9 months after PVI 0.565 ng/ml (±0.146). There was an increase in the concentration of apelin 3 months and 9 months after the PVI by 0.163 ng/ml (p= 0.07) and by 0.266 ng/ml (p = 0.01), respectively. The concentration of apelin inversely correlated with the AF burden (r =-0.44, p = 0.03). CONCLUSIONS: Our study showed a signifi cant increase in apelin levels after the reduction of AF burden via PVI and an inverse correlation with AF burden. Apelin might be a promising marker of AF (Tab. 2, Fig. 2, Ref. 28).

Advances in Biological Chemistry, 2014

This review shortly summarized bio-medical activities of purine alkaloids, caffeine (caf), theoph... more This review shortly summarized bio-medical activities of purine alkaloids, caffeine (caf), theophyline (top) and theobromine (tob). Caffeine potentiates the cytotoxicity of a variety of DNA domaging agents. Caffeine increased antitumor activity of some cancerostatic drugs. Caffeine inhibits the carcinogenic activity of cigarette smoke, significantly potentiating the therapeutic effect of acetaminophenol, cyclophosphoramide, enhances lipid oxidation, affects the central nervous system and alters cardiovascular system. Theophyline has expressive anti-inflammatory and antiasthmatic effect, and enhanced mobilization of lipid reduces the brain regional adenylate cyclase activity, facilitates glucose inhibition. Theophyline is muscle relaxant, vasodilator, diuretic and cardiac stimulant. Theobromine increases antitumor activity of adriamycin and doxorubicin, has expressive anti-inflammatory effect and it is classical diureticum. Several examples of caffeine with some organic substrates as well as with copper are also outlined. Increasing activity of the respective drugs in the present of the purine alkaloids can be ascribed to direct interaction as was proved by X-ray data of some caffeine adducts with organic substances as well as Cu(II) complexes.

Phytotherapy Research, Dec 2, 2009

We studied whether Pycnogenol ® (PYC) may attenuate the development of experimental streptozotoci... more We studied whether Pycnogenol ® (PYC) may attenuate the development of experimental streptozotocininduced diabetic cardiomyopathy in rat. In addition, we aimed to study whether PYC affects cardiac oxidative stress and the protein expression of reactive oxygen species (ROS)-producing molecules (gp91 phox-containing NADPH oxidase and NO-signalling proteins). Experimental diabetes mellitus was manifested by hyperglycaemia and impaired cardiac function estimated using left ventricular catheterisation in vivo. PYC lowered fasting plasma glucose and normalized basal cardiac function. Excessive oxidative stress in streptozotocin (STZ) hearts, evidenced by 40% increase (P < 0.05) of thiobarbituric acid reactive substances (TBARS) concentration, was associated with increased expression of gp91 phox (by 75%, P < 0.05), iNOS (by 40%, P < 0.05) and alpha-tubulin (by 49%, P < 0.05), but unchanged expression of eNOS and its alosteric regulators, as compared to CON. PYC failed to affect these expression abnormalities. Our study shows that PYC corrects diabetic cardiac dysfunction, probably by its metabolic and direct radical scavenging activity without affecting the molecular maladaptations of ROS-producing enzymes and cytoskeletal components.

Journal of Interventional Cardiac Electrophysiology, Mar 10, 2021

Oxidative stress is an important contributor to the etiology of atrial fibrillation (AF). Our aim... more Oxidative stress is an important contributor to the etiology of atrial fibrillation (AF). Our aim was to study oxidative stress biomarkers in patients undergoing pulmonary vein isolation (PVI) for paroxysmal AF with radiofrequency catheter ablation and to assess its prognostic value in predicting long-term PVI outcome. In this prospective cohort study, we included 62 patients (mean age 55±8 years, 12 females and 50 males) with paroxysmal AF and implanted ECG loop recorders who underwent PVI. Plasmatic concentrations of advanced glycation end-products (AGEs), fructosamine, advanced oxidation protein products, and thiobarbituric-acid reacting substances were measured before PVI. AF burden (percentage of time spent in AF) was continually assessed during the follow-up period (1063±271 days). Nineteen patients (31%) were defined as optimal responders (oR) with AF burden < 0.5% after PVI. Remaining 43 patients (69%) were defined as sub-optimal responders. Concentration of AGEs was significantly lower in oR by 3.7 g/g (CI: −6.5 to −1.7; P=0.0003). After adjustment for age, sex, BMI, left atrial size, arterial hypertension, and AF burden before PVI, only low concentration of AGEs remained significantly associated with oR (odds ratio: 1.3; P=0.04). AGEs concentration achieved area under the curve of 0.78 for predicting optimal long-term PVI response. AGEs concentration before PVI was associated with long-term PVI outcome in patients with paroxysmal AF. Further research will show if this biomarker could contribute to optimal patient selection for catheter ablation.

European Heart Journal, Aug 2, 2013

This condition is at increased risk for coronary artery disease (CAD) so as an accelerated senesc... more This condition is at increased risk for coronary artery disease (CAD) so as an accelerated senescence has been demonstrated in TD fibroblasts in vitro. Both phenomena, accelerated senescence and accelerated atherosclerosis are known to be associated and supposed to share common, although yet unknown, mechanisms. Methods: We investigated on the replicative skin fibroblast senescence in vitro in a Caucasian homozygous for ABCA1 mutation (Hom), his heterozygous father (Het), both afflicted by a severe and precocious CAD and in a healthy control. The replicative senescence was study together with the ABCG1 and LDLr gene expression to verify a possible parallelism in both phenomena. Results: Hom cells showed a senescent abnormal morphology and markedly reduced growth at all passages in vitro. The cells percentage senescenceassociated β-galactosidase (SA-β-gal) positive was highly increased in Hom compared to Het cells at late replicative status (66.1% vs 41.3% respectively). Hom showed senescence phenotype at early passages, Het at intermediate passages and control at late passages. ABCG1 gene expression was highly increased (about 4-fold) in Hom fibroblasts than in Het cells at early replication cycles (0.44 vs 0.14 arbitrary unit respectively). This difference decreased by the time (0.14 vs. 0.08 arbitrary unit at late cycles). The LDLr gene expression increased, without significant difference in both Hom and Het, along with the replicative passages. Conclusions: The ABCA1 gene defect has an effect on fibroblast senescence in vitro in a "gene dosage way", in heterozygous state the effect is half less than in homozygous state. An increased ABCG1 and LDLr gene expression is shown in parallel with the accelerated senescence. These results highlight the need for further study on the role of ABCA1 gene effects on mechanisms related to cell cholesterol metabolism and cytoskeleton regulation.

Advances in Respiratory Medicine

The aim of this publication is to analyze the topic of high-frequency jet ventilation (HFJV), nam... more The aim of this publication is to analyze the topic of high-frequency jet ventilation (HFJV), namely catheter HFJV (C-HFJV), from a mathematical–physical as well as a clinical point of view. There are known issues with applying anesthesia and artificial lung ventilation (ALV) during surgical procedures in the upper airways, e.g., during bronchoscopy or tracheostomy. The principles, advantages, and disadvantages of HFJV are discussed in context with basic physical principles to clarify the proper use of this method. The basic technical principles of catheter construction, as well as its functional properties from a biophysical point of view, are introduced. Also, the placement of the catheter in the airways, the set-up of the HFJV ventilator, and the indications as well as the risks and contraindications of the use of C-HFJV are analyzed. This leads to the explanation of potentially optimal techniques for C-HFJV applications. In this article, we present the positive effects of C-HFJV...

Journal of Hypertension

Objective: Epicardial adipose tissue (EAT) an ectopic heart adipose, modulates the environment of... more Objective: Epicardial adipose tissue (EAT) an ectopic heart adipose, modulates the environment of both the coronary arteries and myocardium, and has a very different genes expression from that of other fat depots. Numerous studies propose interactions of EAT with the myocardium and show a role in the development of several cardiovascular diseases through complex mechanisms, including gene expression profile, pro-inflammatory and profibrotic proteome, neuromodulation, and metabolism. Design and method: Our study group consisted of 37 patients (7 women, 30 men; age 49±9 years) with end-stage heart failure (NYHAIII-IV) undergoing heart transplantation at the NICD Bratislava. Samples of EAT and left ventricular (LF) myocardium were collected from the mid-anterior to mid-anterolateral segment of LV within 20 min after heart explantation. The expression of 15 genes was analysed by qRT-PCR and SDS-Page/Western blot. Results: The analysed genes are implicated in heart development (VEGFA, PD...

The aim of this publication is to analyze the topic of high-frequency jet ventilation (HFJV), nam... more The aim of this publication is to analyze the topic of high-frequency jet ventilation (HFJV), namely the catheter HFJV (C-HFJV) from a mathematical-physical as well as a clinical point of view. There are known issues with applying anesthesia and artificial lung ventilation (ALV) during surgical procedures in the upper airways, e.g. during bronchoscopy or tracheostomy. The principles, advantages, and disadvantages of HFJV are discussed in context with basic physical principles to clarify the proper use of this method. The basic technical principles of catheter construction, as well as its functional properties from a biophysical point of view, are introduced. Also, the placement of the catheter in the airways, the set-up of the HFJV ventilator, and the indications as well as the risks and contraindications of the use of C-HFJV are analyzed. This leads to the explanation of potentially optimal techniques for C-HFJV applications. In this article, we present the positive effects of C-HF...

Journal of Interventional Cardiac Electrophysiology, 2021

European Heart Journal, 2017

p=.002). At 20±5 months, the success rate was 72% in ≥0.93 and 52% in <0.93 group (log-rank p=0.0... more p=.002). At 20±5 months, the success rate was 72% in ≥0.93 and 52% in <0.93 group (log-rank p=0.003, figure). Conclusion: Increased level of haptoglobin, an inflammation-sensitive protein, immediately following AF-ablation is associated with higher long-term recurrencefree survival. This can be attributed to its potent anti-oxidant activity.

Venozna tromboembolia je zavažný medicinsky, socialny a ekonomický problem. Krvne zrazeniny su pr... more Venozna tromboembolia je zavažný medicinsky, socialny a ekonomický problem. Krvne zrazeniny su pri hĺbkovej venoznej tromboze (HVT) a pľucnej embolii (PE) najvacsim neocakavaným „zabijakom“ hospitalizovaných pacientov vo vyspelých krajinach. Testovanie hladiny D-dimeru v spojeni s klinickým hodnotenim je už integralnou sucasťou diagnostiky na pritomnosť krvnej zrazeniny. Ale vzhľadom k tomu, že vacsina sucasných kvantitativnych dostupných D-dimer testov sa robi v laboratoriu, je toto testovanie obmedzene na nemocnicne kliniky. Analýza sucasnej medicinskej praxe a pristupných testov indikuje, že prakticki lekari v primarnej starostlivosti na pohotovosti a v ambulanciach by uvitali pristup k spoľahlivemu, jednoduchemu D-dimer testu, cim by zvýsili kvalitu svojej starostlivosti smerom k pacientom, zvýsili by zdravotnu starostlivosť ohľadne diagnostiky a liecby HVT a zlepsili by vyhliadky pacientov.

Global Heart, 2018

Global Heart, 2016

Introduction: About 20% of patients have atypical atrial flutter circuits. Among these, lower loo... more Introduction: About 20% of patients have atypical atrial flutter circuits. Among these, lower loop flutter (LLF), in which the impulse goes around the inferior vena cava (IVC), has been described. The three-dimensional mapping allowing characterization of these circuits have been necessary to effective ablation. Despite their advantages, these are usually costly and not always available. Here we present the case of a 67 y/o male patient with history of chronic heart disease where the ablation of a LLF was done only using conventional mapping and fluoroscopy. Objectives: Describe entrainment mapping and ablation of a LLF, using conventional fluoroscopy. Methods: The patient arrived with congestive heart failure. His electrocardiogram showed atrial frequency of 160 bpm and 4:1 atrioventricular conduction ratio. LVEF of 43%, dilated right chambers and pulmonary hypertension were reported. An electrophysiologic study to define the mechanism of arrhythmia and possible treatment was decided. A decapolar catheter into the coronary sinus, a duodecapolar one in the lateral wall of the right atrium and another for mapping the cavotricuspid isthmus were set. After observing entrainment values, a blockade line from the point of the crista terminalis (CT) with double potential to the back edge of the IVC and through the isthmus was conducted using an 8-mm tip ablation catheter. Results: The activation sequence was counterclockwise at the lateral wall and from right to left in the coronary sinus. Results of entrainment are shown in the figure. During the line of ablation from the CT to the IVC, the tachycardia cycle increased in 90 ms and appearance of double potential was observed. New entrainment of the isthmus showed PPI-TCL in 10 ms. Consequently, the ablation line was extended through it. When the blockade was completed, sinus rhythm was obtained. The differential stimulation from the lateral wall confirmed bidirectional isthmus block. Conclusion: In a LLF there is recirculation of the impulse around the IVC, with a shortcircuit through the CT and a loop that simultaneously flows through the cavotricuspid isthmus. The activation sequence is in most cases clockwise but as in the current case, it could be counterclockwise, suggesting apparent dependence of the isthmus. In the presented example, the entrainment from different points allowed inferring the circuit and the ablation procedure was successfully performed using conventional methods.

European Journal of Heart Failure, Jan 28, 2009

Global heart, Dec 1, 2018

Bratislavské lekárske listy, 2021

Canadian Journal of Physiology and Pharmacology, Nov 1, 2016

International Journal of Molecular Sciences, Oct 5, 2016

Bratislavské lekárske listy, 2020

Advances in Biological Chemistry, 2014

Phytotherapy Research, Dec 2, 2009

Journal of Interventional Cardiac Electrophysiology, Mar 10, 2021

European Heart Journal, Aug 2, 2013

Advances in Respiratory Medicine

Journal of Hypertension

The aim of this publication is to analyze the topic of high-frequency jet ventilation (HFJV), nam... more The aim of this publication is to analyze the topic of high-frequency jet ventilation (HFJV), namely the catheter HFJV (C-HFJV) from a mathematical-physical as well as a clinical point of view. There are known issues with applying anesthesia and artificial lung ventilation (ALV) during surgical procedures in the upper airways, e.g. during bronchoscopy or tracheostomy. The principles, advantages, and disadvantages of HFJV are discussed in context with basic physical principles to clarify the proper use of this method. The basic technical principles of catheter construction, as well as its functional properties from a biophysical point of view, are introduced. Also, the placement of the catheter in the airways, the set-up of the HFJV ventilator, and the indications as well as the risks and contraindications of the use of C-HFJV are analyzed. This leads to the explanation of potentially optimal techniques for C-HFJV applications. In this article, we present the positive effects of C-HF...

Journal of Interventional Cardiac Electrophysiology, 2021

European Heart Journal, 2017

Global Heart, 2018

Global Heart, 2016