Nina Japundzic-Zigon

Physiological mechanisms in regulation of blood pressure fast frequency variations.

Spectral analysis of blood pressure fast oscillations (short-term variability), both in humans and animals, reveals three major frequential domains: the very low-, low- and the high-frequency domain. In this paper, experimental data providing evidence for physiological mechanisms involved in the regulation of blood pressure oscillations such as sympathetic nervous system, renin-angiotensin system, NO, respiration, heart function, and circulating blood volume are reviewed. In addition, novel evidence is provided by the author for vasopressin modulation of the low- and high-frequency blood pressure components. This review suggests that the multiplicity of factors involved in the genesis of the blood pressure spectral components imply utmost caution in interpreting spectral results.

The hypothalamic-neurohypophyseal system: from genome to physiology

The elucidation of the genomes of a large number of mammalian species has produced a huge amount of data on which to base physiological studies. These endeavours have also produced surprises, not least of which has been the revelation that the number of protein coding genes needed to make a mammal is only 22 333 (give or take). However, this small number belies an unanticipated complexity that has only recently been revealed as a result of genomic studies. This complexity is evident at a number of levels: (i) cis‐regulatory sequences; (ii) noncoding and antisense mRNAs, most of which have no known function; (iii) alternative splicing that results in the generation of multiple, subtly different mature mRNAs from the precursor transcript encoded by a single gene; and (iv) post‐translational processing and modification. In this review, we examine the steps being taken to decipher genome complexity in the context of gene expression, regulation and function in the hypothalamic‐neurohypophyseal system (HNS). Five unique stories explain: (i) the use of transcriptomics to identify genes involved in the response to physiological (dehydration) and pathological (hypertension) cues; (ii) the use of mass spectrometry for single‐cell level identification of biological active peptides in the HNS, and to measure in vitro release; (iii) the use of transgenic lines that express fusion transgenes enabling (by cross‐breeding) the generation of double transgenic lines that can be used to study vasopressin (AVP) and oxytocin (OXT) neurones in the HNS, as well as their neuroanatomy, electrophysiology and activation upon exposure to any given stimulus; (iv) the use of viral vectors to demonstrate that somato‐dendritically released AVP plays an important role in cardiovascular homeostasis by binding to V1a receptors on local somata and dendrites; and (v) the use of virally‐mediated optogenetics to dissect the role of OXT and AVP in the modulation of a wide variety of behaviours.

Temporal analysis of the spontaneous baroreceptor reflex during mild emotional stress in the rat

The effect of emotional stress on the spontaneous baroreceptor reflex (sBRR) in freely moving rats was investigated. Six male Wistar rats equipped with an intra-arterial polyethylene catheter were exposed to a 2-min air-jet stress. For time course analysis of the sBRR response to stress, the records of systolic blood pressure (SBP) and pulse interval (PI) were divided into five regions: baseline (BASELINE), acute exposure to air-jet stress (STRESS), immediate recovery (IMMED. RECOVERY), remaining recovery (RECOVERY), and delayed response (DELAYED RESPONSE). In addition to sBRR sensitivity and effectiveness, we introduce the sequence coverage area and its median for evaluation of the sBRR operating range and set point. During exposure to STRESS and IMMED. RECOVERY, sBRR sensitivity was preserved, its effectiveness was decreased, its operating range was enlarged, and the set point was shifted towards higher SBP and lower PI values. According to the joint symbolic dynamics analysis, the SBP and PI relationship became less predictable hence more prone to respond to stress. In RECOVERY the parameters regained baseline values and DELAYED RESPONSE occurred during which re-setting of sBRR was noted. It follows that emotional stress modulates sBRR differentially during the time course of stress and recovery, affecting both linearity and unpredictability of the BP and PI relationship.

Effects of nonpeptide V1a and V2 antagonists on blood pressure fast oscillations in conscious rats.

This paper describes the effects of vasopressin nonpeptide selective V1a (OPC-21268) and V2 (OPC-31260) antagonists on fast blood pressure (BP) oscillations in conscious non-haemorrhaged and haemorrhaged rats. Equidistant sampling at 20 Hz allowed direct spectral analysis of BP on 30 overlapping 2048 point-time series. In non-haemorrhaged rats, V1a antagonist (5 mg/kg; i.v) reduced BP and low-frequency (LF-BP) component while subsequent administration of V2 antagonist (1 mg/kg; i.v) reversed these changes and enhanced the very low-frequency (VLF-BP) component. In haemorrhaged rats (5-15 ml/kg/min) V2 antagonist pre-treatment enhanced the VLF-BP component during normotensive bleeding, while the V1a antagonist pre-treatment modified BP variability after hypotensive haemorrhage by enhancing the HF-SBP component. The results suggest that under normotensive conditions vasopressin by the stimulation of both V1a and V2 receptors buffers BP variability in the VLF-BP frequency domain. In addition, under hypotensive conditions vasopressin, by the stimulation of V1a receptors buffers the respiration-induced HF-BP oscillation.

Unbiased entropy estimates in stress: A parameter study

This study proposes a method for obtaining a stable working point that enables the unbiased estimates of the approximate entropy and the sample entropy. Pattern length, normalized threshold, time delay and tines series length are levels of freedom that are considered. Pulse interval signals used for the experiment are recorded from laboratory animals with different likelihood of developing cardiovascular disease--normal and borderline hypertensive rats--exposed to the acute and to the chronic stress. It is shown that the threshold level is the major source of the instability, and that the generally accepted and widely used methods for a threshold choice may lead to an incorrect psychological interpretation. A method for the threshold level correction is proposed.

Environmental stress: Approximate entropy approach revisited

Radiotelemetred male Wistar outbrad rats and Borderline Hypertensive rats (BHR) were exposed to acute and chronic environmental stress. Approximate entropy (ApEn) approach is applied in order to investigate the pulse interval (PI) response to two different types of environmental stress: shaker and restrain stress. The performance of ApEn method was evaluated from the parameter selection point of view. The purpose of the study is to quantify the complexity of response to stress and period of recovery after the stress in order to gain an insight in consequences of chronic stress exposure.

The flip-flop effect in entropy estimation

The paper investigates the flip-flop effect in entropy estimates: approximate, sample and fuzzy. It was tested in signals recorded from male rats, Wistar ones and borderline hypertensive ones, exposed to various types of stress - shaker and restraint. The occurrence of flip-flop effect cannot be predicted, so the parameters of entropy estimates must be chosen in a way that this unwanted occurrence should be avoided.

Joint Symbolic Dynamic of Cardiovascular Time Series of Rats

Insight in complex heart rate and blood pressure interactions reveals the most important aspects of autonomic control. Our main interest was in baroreceptor reflex (BRR), the most important autonomic cardiovascular reflex. We evaluated the joint symbolic dynamics of heart rate and blood pressure variations in assessing the BRR by opening the BRR loop at different levels using pharmacological blockade of β- adrenergic, α-adrenergic and M-cholinergic receptors. Experiments were done in conscious telemetred Wistar out bred male rats. The observed changes between experimental groups are promising for use of symbolic dynamic method in assessment of impaired autonomic control of the cardiovascular system.

Binarized cross-approximate entropy in crowdsensing environment

OBJECTIVES Personalised monitoring in health applications has been recognised as part of the mobile crowdsensing concept, where subjects equipped with sensors extract information and share them for personal or common benefit. Limited transmission resources impose the use of local analyses methodology, but this approach is incompatible with analytical tools that require stationary and artefact-free data. This paper proposes a computationally efficient binarised cross-approximate entropy, referred to as (X)BinEn, for unsupervised cardiovascular signal processing in environments where energy and processor resources are limited. METHODS The proposed method is a descendant of the cross-approximate entropy ((X)ApEn). It operates on binary, differentially encoded data series split into m-sized vectors. The Hamming distance is used as a distance measure, while a search for similarities is performed on the vector sets. The procedure is tested on rats under shaker and restraint stress, and compared to the existing (X)ApEn results. RESULTS The number of processing operations is reduced. (X)BinEn captures entropy changes in a similar manner to (X)ApEn. The coding coarseness yields an adverse effect of reduced sensitivity, but it attenuates parameter inconsistency and binary bias. A special case of (X)BinEn is equivalent to Shannons entropy. A binary conditional entropy for m =1 vectors is embedded into the (X)BinEn procedure. CONCLUSION (X)BinEn can be applied to a single time series as an auto-entropy method, or to a pair of time series, as a cross-entropy method. Its low processing requirements makes it suitable for mobile, battery operated, self-attached sensing devices, with limited power and processor resources.

Dependency Structures in Differentially Coded Cardiovascular Time Series

Objectives. This paper analyses temporal dependency in the time series recorded from aging rats, the healthy ones and those with early developed hypertension. The aim is to explore effects of age and hypertension on mutual sample relationship along the time axis. Methods. A copula method is applied to raw and to differentially coded signals. The latter ones were additionally binary encoded for a joint conditional entropy application. The signals were recorded from freely moving male Wistar rats and from spontaneous hypertensive rats, aged 3 months and 12 months. Results. The highest level of comonotonic behavior of pulse interval with respect to systolic blood pressure is observed at time lags τ = 0, 3, and 4, while a strong counter-monotonic behavior occurs at time lags τ = 1 and 2. Conclusion. Dynamic range of aging rats is considerably reduced in hypertensive groups. Conditional entropy of systolic blood pressure signal, compared to unconditional, shows an increased level of discrepancy, except for a time lag 1, where the equality is preserved in spite of the memory of differential coder. The antiparallel streams play an important role at single beat time lag.