Heart rate variability analysis based on time-frequency representation and entropies in hypertrophic cardiomyopathy patients.

In hypertrophic cardiomyopathy (HCM) patients there is an increased risk of premature death, which can occur with little or no warning. Furthermore, classification for sudden cardiac death on patients with HCM is very difficult. The aim of our study was to improve the prognostic value of heart rate variability (HRV) in HCM patients, giving insight into changes of the autonomic nervous system. In this way, the suitability of linear and nonlinear measures was studied to assess the HRV. These measures were based on time-frequency representation (TFR) and on Shannon and Rényi entropies, and compared with traditional HRV measures. Holter recordings of 64 patients with HCM and 55 healthy subjects were analyzed. The HCM patients consisted of two groups: 13 high risk patients, after aborted sudden cardiac death (SCD); 51 low risk patients, without SCD. Five-hour RR signals, corresponding to the sleep period of the subjects, were considered for the analysis as a comparable standard situation. These RR signals were filtered in the three frequency bands: very low frequency band (VLF, 0-0.04 Hz), low frequency band (LF, 0.04-0.15 Hz) and high frequency band (HF, 0.15-0.45 Hz). TFR variables based on instantaneous frequency and energy functions were able to classify HCM patients and healthy subjects (control group). Results revealed that measures obtained from TFR analysis of the HRV better classified the groups of subjects than traditional HRV parameters. However, results showed that nonlinear measures improved group classification. It was observed that entropies calculated in the HF band showed the highest statistically significant levels comparing the HCM group and the control group, p-value < 0.0005. The values of entropy measures calculated in the HCM group presented lower values, indicating a decreasing of complexity, than those calculated from the control group. Moreover, similar behavior was observed comparing high and low risk of premature death, the values of the entropy being lower in high risk patients, p-value < 0.05, indicating an increase of predictability. Furthermore, measures from information entropy, but not from TFR, seem to be useful for enhanced risk stratification in HCM patients with an increased risk of sudden cardiac death.

Evidence for cytokine-inducible nitric oxide synthesis from L-arginine in patients receiving interleukin-2 therapy.

An interferon-gamma, tumor necrosis factor, and interleukin-1-inducible, high-output pathway synthesizing nitric oxide (NO) from L-arginine was recently identified in rodents. High-dose interleukin-2 (IL-2) therapy is known to induce the same cytokines in patients with advanced cancer. Therefore, we examined renal cell carcinoma (RCC; n = 5) and malignant melanoma (MM; n = 7) patients for evidence of cytokine-inducible NO synthesis. Activity of this pathway was evaluated by measuring serum and urine nitrate (the stable degradation product of NO) during IL-2 therapy. IL-2 administration caused a striking increase in NO generation as reflected by serum nitrate levels (10- and 8-fold increase [P less than 0.001, P less than 0.003] for RCC and MM patients, respectively) and 24-h urinary nitrate excretion (6.5- and 9-fold increase [both P less than 0.001] for RCC and MM patients, respectively). IL-2-induced renal dysfunction made only a minor contribution to increased serum nitrate levels. Metabolic tracer studies using L-[guanidino-15N2]arginine demonstrated that the increased nitrate production was derived from a terminal guanidino nitrogen atom of L-arginine. Our results showing increased endogenous nitrate synthesis in patients receiving IL-2 demonstrate for the first time that a cytokine-inducible, high-output L-arginine/NO pathway exists in humans.

Effects of triiodothyronine replacement on the anemia of chronic renal failure.

Patients and/or experimental animals with chronic renal failure have decreased serum levels of triiodothyronine (T3), a hormone well known for its erythropoietic activity. The following studies were designed in order to determine whether this observed abnormality in T3 metabolism is an important contributory factor to the etiology of the anemia of uremia. Groups of rats were made chronically uremic by a standard 5/6 nephrectomy technique and received slightly above physiological doses of T3 either by intermittent S.C. injections (twice daily) or by continuous infusion from intraperitoneally implanted osmotic minipumps. After 2 weeks of such treatment, and despite a normalization of serum T3 levels, there were no significant changes in the hematocrit, individual red cell mass, or serum erythropoietin levels of the uremic animals given T3 compared to control rats. We conclude that (1) the decreased serum T3 levels observed in uremia are not an important contributory factor to the pathogenesis of the anemia, and (2) treatment with replacement doses of T3 does not result in significant improvement of erythropoiesis.

On the risk of aortic valve replacement surgery assessed by heart rate variability parameters.

In recent years the number of arterial stenosis (AS) patients has grown rapidly and valvular disease is expected to be the next great epidemic. We studied a group of 385 arterial valve replacement (AVR) surgery patients, of whom 16 had died in the postoperational period (up to 30 d after the operation). Each patient had a heart rate variability (HRV) recording made prior to the operation in addition to a full set of medical diagnostics including echocardiography. We formed 16 age, sex, New York Heart Association (NYHA) class, and BMI adjusted control pairs for each person who died in the perioperative period. Our aim was to find indications of the risk from AVR surgery based on the medical data and HRV properties. Besides standard, linear HRV methods, we used indexes of time irreversibility introduced by Guzik (G%), Porta (P%), Ehlers (index E) and Hou (index D). In addition, we analyzed the multiscale multifractal properties of HRV calculating the Hurst surface. The nonlinear analysis methods show statistically significant indications of the risk of AVR surgery in an increase of multifractality and an increase of time irreversibility of the HRV measured prior to the operation.

The effects of locally applied capsaicin on conduction in cutaneous nerves in four mammalian species.

By examination of compound action potentials in the saphenous nerve of the anaesthetized rat it has been shown that capsaicin causes a rapid, dose-dependent, failure of conduction in many C-fibres when applied directly to the nerve. A large reduction in C-fibre conduction occurs with concentrations as low as 110 microM. After a 15-30 min exposure to capsaicin, only partial recovery occurs in 1 h. Similar block of C-fibre conduction occurs in the ferret. However, only smaller, reversible, reductions in C-fibre conduction were seen in the guinea-pig and rabbit, even at the highest concentration of capsaicin used (33 mM). A small reduction in the A delta component of the compound action potential occurred in all four species. In the rat and ferret the effects were much less than those on C-fibres. At high doses, small reversible effects were also seen on the fastest conducting A alpha beta component of the compound action potential in the rat, rabbit and guinea-pig; no effects were seen on the A alpha beta fibres in the ferret. Decreases in amplitude of the compound action potential were accompanied by some slowing of conduction in most cases. The slowing was less than 5% except for the rat A alpha beta and C-fibres and the ferret C-fibres where 9-15% changes occurred at the highest doses of capsaicin. Opening the connective tissue sheath of the nerve did not significantly increase the effectiveness of capsaicin.

Gas chromatographic determination of prostaglandins.

Progress in separation and detection of prostaglandins and the other metabolites of arachidonic acid by means of GC-ECD, GC-MS, and GC-MS-MS in the course of the past fifteen years was reviewed. One discussed the problems of sample preparation, selection of proper chromatographic conditions, and detection modes available. Finally, applications of the methods developed to detection and quantification of prostanoids in biological material was presented.

Receptive field size of hair follicle afferents in rats treated neonatally with capsaicin.

Receptive field parameters of G- and D-hair units were investigated in adult rats given capsaicin as neonates. An air jet stimulator mounted on a two-way micromanipulator was used for accurate mapping of receptive fields. Diameters of G- and D-hair unit receptive fields were similar in both control and treated groups averaging 2.14 and 2.44 mm respectively with a 1.5 X threshold stimulus. It is concluded that the reported expansion of rat spinal cord cutaneous receptive fields following capsaicin treatment does not have any significant peripheral component.

Secretion of atrial natriuretic peptide (ANP) from fish atrial and ventricular myocytes in tissue culture.

Primary cultures of atrial and ventricular myocytes (approx. 1 x 10(5) cells/culture) were prepared from adult teleost fish Gila atraria and maintained for 10 days. Immunoreactive atrial natriuretic peptide (ir-ANP) from fish atrial and ventricular cells was 3.9 and 2.8 ng/culture respectively, values not significantly different. Atriocytes from rat and mouse secreted comparable amounts of ANP which were not significantly different from atrial fish cultures (5.2 and 4.3 ng/culture). In contrast, their ventricular myocytes secreted only small quantities of ANP (0.8 and 0.3 ng/culture). When analyzed by reversed-phase HPLC, the media of both fish atrial and ventricular myocytes contained a peptide which exhibited properties similar to authentic human ANP (Ser 99-Tyr 126), suggesting a significant degree of sequence homology between fish and mammalian ANP. Fish ventricular cells, unlike normal mammalian ventricular cells, secrete substantial quantities of immunoreactive-ANP.

Potentiometric determination of chlorides with an "Air-Gap" cyanide sensor.

A new electroanalytical method for determining chloride ions with an Air-Gap cyanide sensor system is described. The method is based on the reaction of chloride with mercury(II) cyanide in dilute sulphuric acid. This reaction leads to hydrogen cyanide which can be determined with an Air-Gap cyanide sensor. Optimum concentrations of mercury(II) cyanide and sulphuric acid were established and an analytical curve was prepared for 1 x 10(-1)-1 x 10(-5)M Cl(-). The slope of the calibration curve was equal to 62.8 mV/log C. The correlation coefficient (R) was equal to 0.9992. The method can determine chloride with good results in high saline solutions and in the presence of surfactants, which is in contrast to direct potentiometry with a chloride electrode. The method was applied for chloride determination in fuses used for initiating explosions. The chlorides were determined both in the raw materials used to prepare the fuse braids and in the other fuse components. Chloride was also determined in drinking water and river water. In dependence of source, chloride amount analyzed in drinking water was in the range 2.18-182.6 mg/l. and 25.8 mg/l. in river water. A comparative analysis was carried out. In the first case, chloride was determined by a turbidimetric method, whereas in the second one by potentiometric titration against a chloride-ISE.

Analysis of vanadium-titanium ores and alloys.

A new spectrophotometric method for determining titanium in vanadium-titanium ore with 2,2'-biquinoxalyl was developed. The analytical procedure to dissolve samples and separate titanium from vanadium and tin was elaborated as well. Furthermore, vanadium and iron were determined in the ore investigated.

Direct observation of homoclinic orbits in human heart rate variability.

Homoclinic trajectories of the interbeat intervals between contractions of ventricles of the human heart are identified. The interbeat intervals are extracted from 24-h Holter ECG recordings. Three such recordings are discussed in detail. Mappings of the measured consecutive interbeat intervals are constructed. In the second and in some cases in the fourth iterate of the map of interbeat intervals homoclinic trajectories associated with a hyperbolic saddle are found. The homoclinic trajectories are often persistent for many interbeat intervals, sometimes spanning many thousands of heartbeats. Several features typical for homoclinic trajectories found in other systems were identified, including a signature of the gluing bifurcation. The homoclinic trajectories are present both in recordings of heart rate variability obtained from patients with an increased number of arrhythmias and in cases in which the sinus rhythm is dominant. The results presented are a strong indication of the importance of deterministic nonlinear instabilities in human heart rate variability.

[Ambulatory 24-hour blood pressure monitoring in patients with resistant hypertension]. / Rejestracja 24-godzinna cisnienia tetniczego krwi u chorych z tzw. Opornym nadcisnieniem tetniczym.

The aim of the study was to assess the usefulness of 24-hour blood pressure (BP) and heart rate (HR) monitoring in patients with "resistant" hypertension. 30 patients (44.1 +/- 9.9 years) with diastolic BP 100 mm Hg or more in spite of treatment with three or more antihypertensive drugs were studied. Ambulatory recording of BP and HR was performed by means of Del Mar Avionics monitoring system 9000. Mean recording time was 21.5 hours and mean number of measurements during one recording--56.7. Mean ambulatory systolic and diastolic BP values were significantly lower than mean value of three casual measurements (146.0 +/- 24.6 vs 171.5 +/- 21.2 mm Hg for systolic and 97.2 +/- 11.3 vs 110.4 +/- 7.5 mm Hg for diastolic BP p less than 0.01) In 14 (46.6%) systolic BP and in 10 patients (33.3%) diastolic BP were normal. The patients with normal and abnormal ambulatory BP recordings did not differ in regard to age and mean clinic BP levels. However, patients with abnormal ambulatory BP recordings were more often overweight and showed a greater frequency of left ventricular hypertrophy and family history of hypertension and its complications. The results of the study show that ambulatory BP monitoring may be of value in assessing the response to antihypertensive treatment in patients with so called resistant hypertension as judged on the basis of clinic pressure.

[Coronary ultrasonography. More exact than coronary angiography? Description of two case histories]. / Ultrasonografia sródnaczyniowa tetnic wiencowych. Dokladniejsza niz koronarografia? Opis dwóch przypadków.

Coronary angiography as the "golden standard" in diagnostic imaging, guiding and assessing the results of interventional therapy has well known limitations inherent to the two dimensional imaging of three dimensional structures. Intravascular ultrasonography provides cross-sectional images of coronary artery, allowing an accurate calculation of cross-sectional luminal area and assessment of the degree of eccentricity of plaque and its structure including fissures, dissections and intracoronary thrombi. Case 1: Coronary angiography was performed in a 60 y. male patient with unstable angina revealing only a 40% stenosis in proximal LAD. The inconsistency of clinical presentation with angiography findings led to perform an intravascular ultrasound (IVUS) examination of LAD. The angiographic 40% stenosis was found to be over 80% on IVUS. Subsequent PTCA procedure led to a good IVUS and clinical result with no obvious changes in angiography. Case 2: PTCA of 80% Cx stenosis was performed with good immediate angiographic result, without dissection nor residual stenosis. However, IVUS immediately after PTCA assessed a dissection of the plaque with a flap protruding into the lumen. The patient was sent back to coronary angiography several hours later with clinical and ecg symptoms of acute myocardial ischemia. An important, occlusive dissection was found at the PTCA site. Angioplasty was performed again restoring a wide lumen at intervention site. IVUS was able to clarify the ambiguous angiographic findings with an important impact on interventional therapy. The immediate results of invasive procedures were readily and safely assessed by intravascular ultrasound.

[Increased tension on the sympathetic nervous system in arrhythmogenic right ventricular dysplasia. Participation in etiopathogenesis?]. / Wzmozone napiecie ukladu sympatycznego w arytmogennej dysplazji prawej komory. Udzial w etiopatogenezie?

UNLABELLED: To evaluate the suspected role of sympathetic nerve tone in pathogenesis of arrhythmogenic right ventricle dysplasia (ARVD), noradrenaline (NOR) and adrenaline (AD) plasma levels were determined by radioenzymatic method in 10 pts with ARVD (mean age 36 y, VT-8 pts, syncope-5) at rest and during peak exercise. 9 healthy men (mean age 28 y) served as control. RESULTS: [table: see text] CONCLUSION: Significant increase of norepinephrine serum level during peak exercise suggests essential role of sympathetic nerve tone in pathogenesis of ARVD.

Multiscale multifractal analysis of heart rate variability recordings with a large number of occurrences of arrhythmia.

Human heart rate variability, in the form of time series of intervals between heart beats, shows complex, fractal properties. Recently, it was demonstrated many times that the fractal properties vary from point to point along the series, leading to multifractality. In this paper, we concentrate not only on the fact that the human heart rate has multifractal properties but also that these properties depend on the time scale in which the multifractality is measured. This time scale is related to the frequency band of the signal. We find that human heart rate variability appears to be far more complex than hitherto reported in the studies using a fixed time scale. We introduce a method called multiscale multifractal analysis (MMA), which allows us to extend the description of heart rate variability to include the dependence on the magnitude of the variability and time scale (or frequency band). MMA is relatively immune to additive noise and nonstationarity, including the nonstationarity due to inclusions into the time series of events of a different dynamics (e.g., arrhythmic events in sinus rhythm). The MMA method may provide new ways of measuring the nonlinearity of a signal, and it may help to develop new methods of medical diagnostics.

Stochastic analysis of heart rate variability and its relation to echocardiography parameters in hypertrophic cardiomyopathy patients.

The heart rate variability of 10 healthy males (age 26 - 4/+ 3 y) and 49 patients with hypertrophic cardiomyopathy (HCM) (25 males, 24 females, age 29.5 - 11.5/+ 10.5 y) was studied. We applied Kramers-Moyal expansion to extract the drift and diffusion terms of the Langevin equation for the RR interval time series. These terms may be used for a stochastic reconstruction of the time series and for description of the properties of heart rate variability. New parameters characterizing the diffusion term are proposed: the coefficients of the linear fit to the left (LCF) and right (RCF) branch of the dependence of the diffusion term on the rescaled heart rate. Relations of the new parameters to classical echocardiography parameters were studied. Using the relation between the difference LCF-RCF and the left ventricular systolic diameter, the HCM patients studied were divided into three groups. In addition, comparison of the properties of the heart rate variability in the HCM group with that obtained for the healthy young men showed that the parameter LCF-RCF may be treated as a measure of the effect of HCM on heart rate variability and may have diagnostic value.

Kramers-Moyal coefficients in the analysis and modeling of heart rate variability.

Modeling of recorded time series may be used as a method of analysis for heart rate variability studies. In particular, the extraction of the first two Kramers-Moyal coefficients has been used in this context. Recently, the method was applied to a wide range of signal analysis: from financial data to physiological and biological time series. Modeling of the signal is important for the prediction and interpretation of the dynamics underlying the process. The method requires the determination of the Markov time. Obtaining the drift and diffusion term of the Kramers-Moyal expansion is crucial for the modeling of the original time series with the Langevin equation. Both Tabar [Comput. Sci. Eng. 8, 54 (2006)] and T. Kuusela [Phys. Rev. E 69, 031916 (2004)] suggested that these terms may be used to distinguish healthy subjects from those with heart failure. The research groups applied a somewhat different methodology and obtained substantially different ranges of the Markov time. We show that the two studies may be considered consistent with each other as Kuusela analyzed 24 h recordings while Tabar analyzed daytime and nighttime recordings, separately. However, both groups suggested using the Langevin equation for modeling of time series which requires the fluctuation force to be a Gaussian. We analyzed heart rate variability recordings for ten young male (age 26-4+3 y ) healthy subjects. 24 h recordings were analyzed and 6-h-long daytime and nighttime fragments were selected. Similar properties of the data were observed in all recordings but all the nighttime data and seven of the ten 24 h series exhibited higher-order, non-negligible Kramers-Moyal coefficients. In such a case, the reconstruction of the time series using the Langevin equation is impossible. The non-negligible higher-order coefficients are due to autocorrelation in the data. This effect may be interpreted as a result of a physiological phenomenon (especially occurring for nighttime data): respiratory sinus arrhythmia (RSA). We detrended the nighttime recordings for the healthy subjects and obtained an asymmetry in the dependence of the diffusion term on the rescaled heart rate. This asymmetry seems to be an effect of different time scales during the inspiration and the expiration phase of breathing. The asymmetry was significantly decreased in the diffusion term found for detrended nighttime recordings obtained from five hypertrophic cardiomyopathy (HCM) patients. We conclude that the effect of RSA is decreased in the heart rate variability of HCM patients-a result which may contribute to a better medical diagnosis by supplying a new quantitative measure of RSA.

Nonlinear oscillator model reproducing various phenomena in the dynamics of the conduction system of the heart.

A dedicated nonlinear oscillator model able to reproduce the pulse shape, refractory time, and phase sensitivity of the action potential of a natural pacemaker of the heart is developed. The phase space of the oscillator contains a stable node, a hyperbolic saddle, and an unstable focus. The model reproduces several phenomena well known in cardiology, such as certain properties of the sinus rhythm and heart block. In particular, the model reproduces the decrease of heart rate variability with an increase in sympathetic activity. A sinus pause occurs in the model due to a single, well-timed, external pulse just as it occurs in the heart, for example due to a single supraventricular ectopy. Several ways by which the oscillations cease in the system are obtained (models of the asystole). The model simulates properly the way vagal activity modulates the heart rate and reproduces the vagal paradox. Two such oscillators, coupled unidirectionally and asymmetrically, allow us to reproduce the properties of heart rate variability obtained from patients with different kinds of heart block including sino-atrial blocks of different degree and a complete AV block (third degree). Finally, we demonstrate the possibility of introducing into the model a spatial dimension that creates exciting possibilities of simulating in the future the SA the AV nodes and the atrium including their true anatomical structure.