Péter Makra

SIGNAL-TO-NOISE RATIO GAIN IN NON-DYNAMICAL AND DYNAMICAL BISTABLE STOCHASTIC RESONATORS

It has recently been reported that in some systems showing stochastic resonance, the signal-to-noise ratio (SNR) at the output can significantly exceed that at the input; in other words, SNR gain is possible. We took two such systems, the non-dynamical Schmitt trigger and the dynamical double wellpotential, and using numerical and mixed-signal simulation techniques, we examined what SNR gains these systems can provide. In the non-linear response limit, we obtained SNR gains much greater than unity for both systems. In addition to the classical narrow-band SNR definition, we also measured the ratio of the total power of the signal to the power of the noise part, and it showed even better signal improvement. Here we present a brief review of our results, and scrutinise, for both the Schmitt-trigger and the double well potential, the behaviour of the SNR gain by stochastic resonance for different signal amplitudes and duty cycles. We also discuss the mechanism of providing gains greater than unity.

Relevance of anaesthesia for dofetilide-induced torsades de pointes in α1-adrenoceptor-stimulated rabbits

No information is available concerning the effects of anaesthetics in the most frequently used in vivo pro‐arrhythmia model. Accordingly, in this study we examined the effect of pentobarbital, propofol or α‐chloralose anaesthesia on the pro‐arrhythmic activity of the class III anti‐arrhythmic dofetilide in α1‐adrenoceptor‐stimulated rabbits.

Human autonomic responses to blood donation

In order to characterize autonomic responses to acute volume loss, supine ECG, blood pressure (BP) and uncalibrated breathing signal (UBS) recordings were taken before and after blood donation in 48 healthy volunteers. Time and frequency domain parameters of RR interval (RRI), BP and UBS variability were determined. Baroreflex gain was calculated by the technique of the spontaneous sequences and cross-spectral analysis. The systolic (SAP), diastolic (DAP) and mean BP (MAP) increased after the blood withdrawal. The central frequency of breathing and mean heart rate did not change. RRI variability increased in low frequency band (LF), tended to decrease in high frequency band (HF). Systolic BP variability increased in both frequency bands, but was statistically significant only in the high frequency band. Diastolic BP power increased in both frequencies. From the different baroreflex gain estimates, up sequence BRS and HF alpha index decreased significantly. The phase angle between RRI and systolic blood pressure powers in LF band did not change (-58 +/- 24 degrees and -54 +/- 26 degrees ). In the high frequency range, the phase became more negative (-1 +/- 29 degrees and -17 +/- 32 degrees, p = 0.001). The withdrawal of 350-400 ml blood in 5 min resulted in sympathetic activation, which was reflected in increased systolic, diastolic and mean BP. The increased BP oscillation was a sensitive marker of the minor volume depletion. This was coupled by increased RRI oscillation via baroreflex mechanisms in the LF band. Changes in the RRI and BP oscillations in the HF band showed no similar coupling. That points to the fact that RRI oscillations in this band should not be explained entirely by baroreflex mechanisms. Vagal withdrawal was reflected in decreased root mean square of successive differences (RMSSD), decreased HF RRI power and decreased up sequence BRS.

The role of the Na+/Ca2+ exchanger, INa and ICaL in the genesis of dofetilide-induced torsades de pointes in isolated, AV-blocked rabbit hearts

Background and purpose:  The Na+/Ca2+ exchanger (NCX) may contribute to triggered activity and transmural dispersion of repolarization, which are substrates of torsades de pointes (TdP) type arrhythmias. This study examined the effects of selective inhibition of the NCX by SEA0400 on the occurrence of dofetilide‐induced TdP.

Biomarkers and endogenous determinants of dofetilide-induced torsades de pointes in α1-adrenoceptor-stimulated, anaesthetized rabbits

Torsades de pointes (TdP) liability is a stochastic event, which indicates that unidentified factors have an important role in facilitating the initiation of TdP by increasing the probability of TdP occurrence. We sought to identify factors that facilitate drug‐induced TdP.

Edaq530: a transparent, open-end and open-source measurement solution in natural science education

We present Edaq530, a low-cost, compact and easy-to-use digital measurement solution consisting of a thumb-sized USB-to-sensor interface and measurement software. The solution is fully open-source, our aim being to provide a viable alternative to professional solutions. Our main focus in designing Edaq530 has been versatility and transparency. In this paper, we shall introduce the capabilities of Edaq530, complement it by showing a few sample experiments, and discuss the feedback we have received in the course of a teacher training workshop in which the participants received personal copies of Edaq530 and later made reports on how they could utilize Edaq530 in their teaching.

High incidence of adverse cerebral blood flow responses to spreading depolarization in the aged ischemic rat brain.

Spreading depolarizations (SDs) occur spontaneously in the brain after stroke, exacerbate ischemic injury, and thus emerge as a potential target of intervention. Aging predicts worse outcome from stroke; yet, the impact of age on SD evolution is not clear. Cerebral ischemia was induced by bilateral common carotid artery occlusion in young (8-9 weeks old, n = 8) and old (2 year olds, n = 6) anesthetized rats. Sham-operated animals of both age groups served as control (n = 12). Electrocorticogram, direct current potential, and cerebral blood flow (CBF) variations were acquired via a small craniotomy above the parietal cortex. SDs were elicited by KCl through a second craniotomy distal to the recording site. Ischemia and age delayed the recovery from SD. CBF decreased progressively during ischemia in the old animals selectively, and inverse neurovascular coupling with SD evolved in the old but not in the young ischemic group. We propose that (mal)adaptation of cerebrovascular function with aging impairs the SD-related CBF response, which is implicated in the intensified expansion of ischemic damage in the old brain.

Increased Cardiovascular Reactivity to Acute Stress and Salt-Loading in Adult Male Offspring of Fat Fed Non-Obese Rats

Diet-induced obesity in rat pregnancy has been shown previously to be associated with consistently raised blood pressure in the offspring, attributed to sympathetic over-activation, but the relative contributions to this phenotype of maternal obesity versus raised dietary fat is unknown. Sprague-Dawley female rats were fed either a control (4.3% fat, n = 11) or lard-enriched (23.6% fat, n = 16) chow 10 days prior to mating, throughout pregnancy and lactation. In conscious adult (9-month-old) offspring cardiovascular parameters were measured (radiotelemetry). The short period of fat-feeding did not increase maternal weight versus controls and the baseline blood pressure was similar in offspring of fat fed dams (OF) and controls (OC). However, adult male OF showed heightened cardiovascular reactivity to acute restraint stress (p<0.01; Δ systolic blood pressure (SBP) and Δheart rate (HR)) with a prolonged recovery time compared to male OC. α1/β-adrenergic receptor blockade normalised the response. Also, after dietary salt-loading (8%-NaCl ad libitum for 1 week) male OF demonstrated higher SBP (p<0.05) in the awake phase (night-time) and increased low/high frequency ratio of power spectral density of HR variability versus OC. Baroreflex gain and basal power spectral density components of the heart rate or blood pressure were similar in male OF and OC. Minor abnormalities were evident in female OF. Fat feeding in the absence of maternal obesity in pregnant rats leads to altered sympathetic control of cardiovascular function in adult male offspring, and hypertension in response to stressor stimuli.

Advancing age and ischemia elevate the electric threshold to elicit spreading depolarization in the cerebral cortex of young adult rats.

Spreading depolarizations of long cumulative duration have been implicated in lesion development and progression in patients with stroke and traumatic brain injury. Spreading depolarizations evolve less likely in the aged brain, but it remains to be determined at what age the susceptibility to spreading depolarizations starts to decline, especially in ischemia. Spreading depolarizations were triggered by epidural electric stimulation prior and after ischemia induction in the cortex of 7–30 weeks old anesthetized rats (n = 38). Cerebral ischemia was achieved by occlusion of both common carotid arteries. Spreading depolarization occurrence was confirmed by the acquisition of DC potential and electrocorticogram. Cerebral blood flow variations were recorded by laser-Doppler flowmetry. Dendritic spine density in the cortex was determined in Golgi-COX stained sections. Spreading depolarization initiation required increasingly greater electric charge with older age, a potential outcome of consolidation of cortical connections, indicated by altered dendritic spine distribution. The threshold of spreading depolarization elicitation increased with ischemia in all age groups, which may be caused by tissue acidosis and increased K+ conductance, among other factors. In conclusion, the brain appears to be the most susceptible to spreading depolarizations at adolescent age; therefore, spreading depolarizations may occur in young patients of ischemic or traumatic brain injury at the highest probability.

Spreading depolarization remarkably exacerbates ischemia-induced tissue acidosis in the young and aged rat brain

Spreading depolarizations (SDs) occur spontaneously in the cerebral cortex of subarachnoid hemorrhage, stroke or traumatic brain injury patients. Accumulating evidence prove that SDs exacerbate focal ischemic injury by converting zones of the viable but non-functional ischemic penumbra to the core region beyond rescue. Yet the SD-related mechanisms to mediate neurodegeneration remain poorly understood. Here we show in the cerebral cortex of isoflurane-anesthetized, young and old laboratory rats, that SDs propagating under ischemic penumbra-like conditions decrease intra and- extracellular tissue pH transiently to levels, which have been recognized to cause tissue damage. Further, tissue pH after the passage of each spontaneous SD event remains acidic for over 10 minutes. Finally, the recovery from SD-related tissue acidosis is hampered further by age. We propose that accumulating acid load is an effective mechanism for SD to cause delayed cell death in the ischemic nervous tissue, particularly in the aged brain.