Effect of ivabradine, captopril and melatonin on the behaviour of rats in L-nitro-arginine methyl ester-induced hypertension.

Cardiovascular diseases including hypertension are often associated with behavioural alterations. The aim of this study was to show, whether ivabradine, the blocker of If-channel in sinoatrial node, is able to modify the behaviour of rats in L-nitro-arginine methyl ester (L-NAME)-induced hypertension and to compare the effect of ivabradine with captopril and melatonin. 12-week-old male Wistar rats were divided into the following groups: controls, ivabradine (10 mg/kg/24 h), L-NAME (40 mg/kg/24 h), L-NAME + ivabradine, L-NAME + captopril (100 mg/kg/24 h), L-NAME + melatonin (10 mg/kg/24 h). Systolic blood pressure (SBP) and heart rate (HR) were measured by tail-cuff method once a week. The behaviour of rats was investigated during 23-hours in the phenotyper after four weeks of the treatment. Chronic administration of L-NAME induced hypertension without a change in HR. All tested substances partly prevented the increase of SBP, while ivabradine and melatonin also reduced HR. Ivabradine, captopril and melatonin reduced daily food intake, slightly decreased daily water intake and attenuated body weight gain. In L-NAME group, locomotor activity was enhanced by ivabradine, whereas exploratory behaviour was increased by melatonin and captopril. In conclusion, ivabradine, besides its potentially protective hemodynamic actions, does not seem to exert any disturbing effects on behaviour in L-NAME-induced hypertension in rats, while some of its effects were similar to captopril or melatonin. It is suggested that ivabradine used in cardiovascular indications is harmless regarding the effect on behaviour.

Long-term liquid nutrition intake and development of obesity: differences between young and adult rats.

OBJECTIVE: Obesity is particularly associated with an increased consumption of palatable fat and sugar dense food and beverages. Therefore, we examined the effect of a normocaloric liquid diet (Fresubin) with increased carbohydrate content (constituting 55% of calories) on development of obesity in different developmental periods in male Wistar rats. METHODS: Fresubin was provided to 3 groups of rats: the first group received Fresubin immediately after weaning (21st day of age) to the end of experiment (150th day of age) for 5 months; the second group was fed with Fresubin from weaning to adulthood (90th day of age) for 3 months; and the third group received Fresubin only in adulthood (from 90th to 150th day of age) for 2 months. The control group was fed with standard pellet chow from weaning to the end of the experiment. Body weight, food and water intake were periodically measured. After terminating the experiment, the adiposity index was determined. RESULTS: Rats fed with liquid nutrition showed increased energy intake and body weight in comparison with the control rats. Interestingly, while obesity in the juvenile rats developed as late as of 13 weeks after the Fresubin intake, the adult rats fed with liquid nutrition had significantly elevated the body weight already 2 weeks after starting the treatment. Increased adiposity index was observed in both groups of rats fed with Fresubin during the whole study as well as the adulthood. CONCLUSIONS: Our data indicate that feeding of male Wistar rats with a high carbohydrate normocaloric diet results in a substantial development of obesity. Moreover, exposure of juvenile individuals to obesogenic environment leads, after a certain "latent period", to the development of obesity that may reflect low protein content of used liquid diet or higher resistance of juvenile organism to the obesogenic factors. Finally, based on the data obtained we suggest that Fresubin, with respect to its properties, may serve as a diet for the development of obesity which may exemplify an "obesity model" applicable in small laboratory animals.

Diastolic blood pressure as a major determinant of tissue perfusion: potential clinical consequences.

Blood pressure measuring represents a routine investigation in general medicine. In the last decades large studies have determined average blood pressure values all around the world. Large clinical trials have shown that blood pressure reduction irrespective of the used type of therapeutic intervention reduces mortality. Based on the outcomes of these trials current guidelines for hypertension encourage more "aggressive" hypertension treatment compared to recommendations from the past. In clinical practice blood pressure is sometimes reduced even below normotensive values (at least in comparison with pre-treatment levels). However there is evidence that achieving too low levels of diastolic blood pressure during antihypertensive treatment has undesirable effects. Especially in the elderly a diastolic blood pressure reduction below 70 mm Hg should be avoided, because it is associated with increased mortality. A possible explanation of this phenomenon could be that antihypertensive treatment disequilibriates the balance between sufficient perfusion pressure and arteriolar vasodilation, both of which are required for adequate tissue perfusion. Impaired microcirculation, especially in the coronary bed may account for the increased mortality in hypertensive patients with low diastolic blood pressure levels. Thus we support the idea of cautious blood pressure reduction in the elderly. Furthermore, we suggest, that monitoring the level of tissue perfusion in treated hypertensive patients might help to provide individually tailored therapy (Fig. 1, Ref. 9). Full Text (Free, PDF) www.bmj.sk.

High resolution electrocardiography in healthy dogs: time domain parameters and comparison of the non-stationary (Wigner distribution) versus standard stationary frequency domain analysis methods.

Fractionated heart activation can be detected as late potentials from surface recordings of signal-averaged electrocardiograms (SA ECG) which are considered as a marker of sustained ventricular tachycardia. For animal studies, reference values in time and frequency domain analyses are essentially missing. In the present study, we have established reference values in SA ECG time domain analysis and time-frequency representation of heart activation in healthy dogs. A group of 25 healthy mongrel dogs (body weight 12-15 kg) was investigated. Wigner distribution and our modification of Fast Fourier transform (FFT), gliding window FFT, was applied in SA ECG frequency domain analysis. Reference values in time domain SA ECG were established. Time and voltage criteria were adapted to short duration of heart cycle and fast voltage decrement of the QRS complex in dogs. Wigner distribution and gliding window FFT were applied in order to describe mean heart activation in the frequency domain. Contribution of higher frequencies (30-80 Hz) was detected by both frequency analysis methods in the second third of ventricular activation in healthy animals. Presented results could offer a basis for further experimental arrhythmologic studies.

The Nobel Prize in Physiology or Medicine in 2003 to Paul C. Lauterbur, Peter Mansfield for magnetic resonance imaging.

Imaging of human internal organs by exact and non-invasive methods is very important for medical diagnosis, treatment and follow-up. 2003 Nobel Laureates in Physiology or Medicine have made original discoveries in the use of magnetic resonance to visualize different structures. Their discoveries have led to the development of modern magnetic resonance imaging, MRI, which represents a breakthrough in medical diagnostics and research. Atomic nuclei within a strong magnetic field rotate with a frequency depending on the strength of the magnetic field. Their energy can increase if they absorb radio waves with the same frequency (resonance). When atomic nuclei return to their previous energy status, radio waves are emitted. These discoveries were awarded the Nobel Prize in Physics in 1952. During the following decades, magnetic resonance was used mainly for studies of the chemical structure of substances. In the beginning of the 1970s, 2003 Nobel Laureates made pioneering contributions, which later led to the applications of magnetic resonance in medical imaging. Paul Lauterbur (born 1929), Urbana, Illinois, USA, discovered the possibility to create a two-dimensional picture by introducing gradients to a magnetic field. Analysing the characteristics of the emitted radio waves he could determine their origin. This fact made it possible to build up a two-dimensional picture of structures that could not be visualized by other methods. Peter Mansfield (born 1933), Nottingham, England, further developed the utilization of gradients in the magnetic field. He showed, that the signals could be mathematically analysed, which made it possible to develop a useful imaging technique. Mansfield also showed how extremely fast imaging could be. It became technically possible within a decade. Magnetic resonance imaging, MRI, is now a routine method in medical diagnostics. Worldwide, more than 60 million investigations are performed each year, and the method is still rapidly evolving. MRI is often superior to other imaging techniques and significantly improves diagnostics in many diseases. MRI has replaced several invasive methods of examination and in this way has reduced the risk and discomfort of many patients. (Fig. 3, Ref. 3.).

Voltage sum of filtered ECG signal--a sensitive parameter of ventricular activation.

On the basis of the signal averaged ECG (SA ECG) principle the authors analyse the gradually filtered ECG signal (in ranges of 0-120 Hz with increments of 10 Hz). The voltage sums are determined in eight segments of the QRS complex. The described VSF-ECG method (Voltage Sum of Filtered ECG) was applied in a group of healthy probands and in groups of selected patients. The measurements in healthy probands were used to determine the value of standard in healthy subjects. Repeated measurements confirmed a good reproducibility of the VSF-ECG method. The method enables a precise quantification of heart activation progression. VSF-ECG is a method revealing the changes of heart activation progression being not reflected as late potentials. Parameters of the method are indicators of activation splitting upon the infarction area and also an indicator of the electric milieu of the entire heart.

Segmental blood flow through intramyocardial coronary arteries during ventricular systole.

The presented hypothesis assumes, in contrast with the currently prevailing view, that blood continues to flow through the coronary vascular bed even during systole. The contraction of differently oriented myocardial layers closes the penetrating branches of the coronary arteries in the interlayer boundaries. Coronary arteries of a different caliber are during systole under equal intramyocardial pressure. In accordance with the theory of elasticity, the action of an equal external pressure decreases with the lumen of the vessel and, thus, the net effect of these forces will push the blood into smaller vessels within the segment in the layer. This hydrodynamic effect empties the larger coronary arteries during systole so that they are ready for the subsequent massive influx of blood during diastole. The possible applications of this hypothesis in various physiological and pathological conditions are compatible with the present knowledge and might contribute to a more precise understanding of implicated pathophysiological mechanisms.

The antihypertensive treatment and high-resolution electrocardiography.

After six months of antihypertensive treatment the regression of the initially present myocardial hypertrophy was observed: The decrease in blood pressure values is in correlation with the regression of the left ventricular hypertrophy. No correlation with parameters of high-resolution electrocardiography was noted. In one patient, a deterioration of late potentials was observed. It became more pronounced following the treatment. The monitoring of antihypertensive treatment effects by echocardiography and high-resolution electrocardiography may be therefore considered useful, especially in expected regression of the left ventricular hypertrophy. In individual cases of very outstanding regression, there exists the potential possibility of the process, resulting in the risk of arrhythmogenic substrate formation and subsequent generation of dysrhythmias.

Gliding-window fast Fourier transform analysis of the entire QRS complex and the distribution of area ratio peaks in healthy subjects and patients with myocardial infarction.

BACKGROUND: The high-frequency contribution (i.e. 60-120 Hz) within the QRS complex of the surface ECG is supposed to be related to the arrhythmogenic substrate underlying sustained ventricular tachycardia in patients with coronary artery disease. One of the factors that prevents a wider clinical application of spectral analysis based on the fast Fourier transform is the considerable intra-individual variability of its results. This study presents a novel alternative approach of frequency-domain analysis, aimed at minimizing this methodological drawback. METHODS: The proposed method uses gliding-window fast Fourier transform analysis of the signal-averaged ECG to provide values expressing the area ratio for two predefined frequency ranges (60-120 Hz divided by 0-120 Hz). The term gliding window is derived from the methodological principle by which the window analyzed is moved from the onset of the QRS complex into the ST segment. Values of area ratios obtained for every time instant of the interval of gliding are the basis for construction of curves. These are further analyzed in order to find patterns that characterize abnormal ventricular activation, with special emphasis on the identification of arrhythmogenic correlates. RESULTS: In a group of 30 healthy subjects, the distribution of area ratio peaks was characterized according to their value and timing. The distribution of area ratio peaks in 43 patients with myocardial infarction differed substantially from the normal distribution in the control group. The amplitude of the peaks and their timing was not related to the occurrence of late ventricular potentials. CONCLUSION: The method of gliding-window fast Fourier transform analysis eliminates the variability of results obtained by traditional spectral analysis of the ECG signal. A higher number and a different distribution of high-frequency peaks during the QRS complex in postmyocardial infarction patients reflect abnormal ventricular activation. However, late ventricular potentials are not related to a higher proportion of high frequencies in the corresponding time interval within the terminal QRS complex.

Gliding window fast Fourier transform analysis--a new method for discovering the contribution of higher frequencies in signal-averaged ECG.

OBJECTIVE: An attempt to detect the 'parasitic contribution' of high frequencies in the electrocardiogram signal. DESIGN: A new method--gliding window fast Fourier transform analysis (GWFFTA)--was developed. It was applied in healthy subjects and in patients with acute myocardial infarction. SETTING: Faculty of Medicine and University Hospital. PATIENTS: The GWFFTA was used in 29 healthy volunteers and in a group of 30 patients with myocardial infarction, on day 7 to 14 after admission to a coronary unit. INTERVENTION: Noninvasive examination, performed under standard conditions. MAIN RESULTS: GWFFTA provides better reproducible results compared with 'classic' fast Fourier transform analysis. The parasitic contribution of high frequencies within QRS complex and ST segment in patients with acute myocardial infarction is independent of presence or absence of late potentials. Contribution of high frequencies are three times higher in patients with acute myocardial infarction than in healthy probands. CONCLUSIONS: GWFFTA is a reproducible method of detection of high frequencies during whole heart activation. Contribution of high frequencies in patients with acute myocardial infarction reflects the state of the entire myocardium. It is also confirmed by the lack of correlation with the presence or absence of late potentials. Late potentials are more reflective of focal changes.

Special computer graphical method for detection of myocardial infarction.

The application of computer graphics for detection of myocardial infarction is reviewed and a special method is described. It is based on construction of two isointegral maps (Q wave map and ST segment map) realized in contour representation and using the Selvester distribution of the left ventricle.

Does the heart electric activation split upon the infarcted area? An attempt at its detection by high-resolution electrocardiography.

Based on the presumption of the activation front splitting, the authors present their own proposal for the estimation of the myocardial electric activation course and for the detection of micropotentials 'hidden' within QRS complexes by the method of high-resolution electrocardiography. After filtration of QRS complex the values of delta RMS and those of cumulative amplitudes are calculated from the initial and from the terminal parts of QRS complexes. The presence of late potentials is reflected in a slowing down of the termination of activation course. As compared with healthy subjects, a slower rise of activation was observed in patients with myocardial infarction of the anterior wall. The curves of cumulative amplitudes rose very slowly during the first 70 ms of heart ventricle activation, explained according to the hypothesis of authors as being due to splitting of the activation front at the infarction focus. The usefulness of the proposed method was checked in patients with arterial hypertension and left ventricular hypertrophy, and in a group of patients with myocardial infarction. By the construction of cumulative amplitude curves from the onset of filtered QRS complexes, myocardial foci not reflected by 'classic' late potentials can be detected. The partial cumulative amplitudes of the QRS complex are suitable for comparative studies.

Graphic representation of deviations of the cardiac electric field.

The first part of the paper presents a survey of mapping methods in electrocardiography and discusses the present possibilities of graphic representation of individual types of maps of the cardiac electric field (CEF). In the second part of the paper, the authors describe their own method of constructing complete departure maps. The mode of determining the matrix of the departure map surface is given. Four spatial maps--CEF surface, projection of CEF surface, threedimensional departure map, contour departure map--yield in one graphic output the complete departure map. The value of personal computers for diagnostic methods in medicine is being emphasized. The paper is supplemented by graphic outputs performed on the computer EC 1045 and represented by the plotter DIGIGRAF.

Computer graphics and computer animation of the electric heart field.

The authors present in their paper the possibilities of the application of computer graphics and computer animation for visualization of the electric heart field (EHF). They describe the construction of three-dimensional potential maps by the methods of interpolation, perspective projection, hidden line elimination and text generation. They also present a method for making of animation films showing the electric activity of the heart by using 80 three-dimensional potential maps recorded at different intervals over the entire cardiac cycle.