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Telemetric data collection should be standard in modern experimental cardiovascular research

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Abstract

Cardiovascular (CV) health is often expressed by changes in heart rate and blood pressure, the physiological record of which may be affected by moving, anaesthesia, handling, time of day and many other factors in rodents. Telemetry measurement minimises these modulations and enables more accurate physiological recording of heart rate and blood pressure than non-invasive methods. Measurement of arterial blood pressure by telemetry requires implanting a catheter tip into the artery. Telemetry enables us to sample physiological parameters with a high frequency continuously for several months. By measuring the pressure in the artery using telemetry, we can visualize pressure changes over a heart cycle as the pressure wave. From the pressure wave, we can subtract systolic, diastolic, mean and pulse pressure. From the beat-to-beat interval (pressure wave) and the RR' interval (electrocardiogram), we can derive the heart rate. From beat-to-beat variability, we can evaluate the autonomic nervous system's activity and spontaneous baroreflex sensitivity and their impact on CV activity. On a long-term scale, circadian variability of CV parameters is evident. Circadian variability is the result of the circadian system's activity, which synchronises and organises many activities in the body, such as autonomic and reflex modulation of the CV system and its response to load over the day. In the presented review, we aimed to discuss telemetry devices, their types, implantation, set-up, limitations, short-term and long-term variability of heart rate and blood pressure in CV research. Data collection by telemetry should be, despite some limitations, standard in modern experimental CV research.

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... Animals were instrumented with a full-implant telemetry system (see below) to measure LVP, AP, ECG and temperature (Markert et al., 2018;Molcan, 2021). A minimum recovery period of 21 days post-surgery was maintained prior to any experimentation. ...
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Chronic continuous glucose monitoring options for animal research have been very limited due to various technical and biological challenges. We provide an evaluation of a novel telemetry device for continuous monitoring of temperature, activity, and plasma glucose levels in the arterial blood of rats for up to 2 months. In vivo testing in rats including oral glucose tolerance tests (OGTTs) and intraperitoneal glucose tolerance tests (IPGTTs) and ex vivo waterbath testing were performed to evaluate acute and chronic sensor performance. Animal studies were in accordance with the guidelines for the care and use of laboratory animals and approved by the corresponding animal care and use committees (Data Sciences International, Eli Lilly). Results demonstrated the ability to record continuous measurements for 75 days or longer. Bench testing demonstrated a high degree of linearity over a range of 20-850 mg/dL with R (2) = .998 for linear fit and .999 for second order fit (n = 8 sensors). Evaluation of 6 rats over 28 days with 52 daily and OGTT test strip measurements each resulted in mean error of 3.8% and mean absolute relative difference of 16.6%. This device provides significant advantages in the quality and quantity of data that can be obtained relative to existing alternatives such as intermittent blood sampling. These devices provide the opportunity to expand the understanding of both glucose metabolism and homeostasis and to work toward improved therapies and cures for diabetes. © 2015 Diabetes Technology Society.
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Growing evidence shows that intrinsic circadian clocks are tightly related to cardiovascular functions. The diurnal changes in blood pressure and heart rate are well known circadian rhythms. Endothelial function, platelet aggregation and thrombus formation exhibit circadian changes as well. The onset of many cardiovascular diseases (CVDs) or events, such as myocardial infarction, stroke, arrhythmia, and sudden cardiac death, also exhibits temporal trends. Furthermore, there is strong evidence from animal models and epidemiological studies showing that disruption of circadian rhythms is a significant risk factor for many CVDs, and the intervention of CVDs may have a time dependent effect. In this mini review, we summarized recent advances in our understanding of the relationship between circadian rhythm and cardiovascular physiology and diseases including blood pressure regulation and myocardial infarction.
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Under physiological conditions the mammalian circadian system is synchronized to a cyclic environment. The central oscillator in the suprachiasmatic nuclei (SCN) responds predominantly to an external light (L) dark (D) cycle. Peripheral oscillators are more efficiently synchronized by metabolic cues. When the circadian system is exposed to opposing synchronizing cues, peripheral oscillators uncouple from the SCN. To consider influence of phase advances and delays in light regimens mimicking shift work, we analyzed the expression of clock genes (per2, bmal1) and natriuretic peptides (anp, bnp) in the heart of male rats. Experimental groups were exposed to a rotating LD regimen with either 8 h phase advance or delay for 11 weeks. Samples were taken for a 24 h cycle in 4 h intervals. Peripheral oscillators responded to rotating phase advance by decreasing rhythm robustness, while phase delay mostly influenced the phase angle between the acrophase of rhythmic gene expression and the external LD cycle. The expression of anp was arrhythmic in the heart of control rats and was not influenced by rotating LD regimens. The expression of bnp showed a daily rhythm with a nadir during the active phase. The daily rhythm in bnp expression diminished under rotating LD regimen conditions.
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Prenatal hypoxia (PH) has negative consequences on the cardiovascular system in adulthood and can affect the responses to additional insults later in life. We explored the effects of PH imposed during embryonic day 20 (10.5% O 2 for 12 h) on circadian rhythms of systolic blood pressure (BP) and heart rate (HR) in mature male rat offspring measured by telemetry. We evaluated: (1) stability of BP and HR changes after PH; (2) circadian variability of BP and HR after 2 and 5 weeks of exposure to artificial light at night (ALAN; 1–2 lx); and (3) response of BP and HR to norepinephrine. PH increased BP in the dark (134 ± 2 mmHg vs. control 127 ± 2 mmHg; p = 0.05) and marginally in the light (125 ± 1 mmHg vs. control 120 ± 2 mmHg) phase of the day but not HR. The effect of PH was highly repeatable between 21- and 27-week-old PH male offspring. Two weeks of ALAN decreased the circadian variability of HR ( p < 0.05) and BP more in control than PH rats. After 5 weeks of ALAN, the circadian variability of HR and BP were damped compared to LD and did not differ between control and PH rats ( p < 0.05). Responses of BP and HR to norepinephrine did not differ between control and PH rats. Hypoxia at the end of the embryonic period increases BP and affects the functioning of the cardiovascular system in mature male offspring. ALAN in adulthood decreased the circadian variability of cardiovascular parameters, more in control than PH rats.
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New findings: Symmetric Projection Attractor Reconstruction (SPAR) is a relatively new mathematical method which can extract new information pertaining to the morphology and variability of physiological waveforms, such as arterial pulse pressure. Herein, we describe the method's potential utility in more sensitively quantifying cardiovascular changes. We use a simple example of a human tilt table to illustrate these concepts. SPAR can be used on any approximately periodic waveform and may add value to experimental and clinical settings, where such signals are routinely collected. Abstract: Periodic physiological waveform data such as blood pressure, pulse oximetry and ECG are routinely sampled between 100-1000 Hz in preclinical research and in the clinical setting from a wide variety of implantable, beside and wearable monitoring devices. Despite the underlying numerical waveform data being captured at such high-fidelity, conventional analysis tends to reside in only reporting averages of minimum, maximum, amplitude and rate, as single point averages. Whilst these averages are undoubtedly of value, simplifying the data in this way means that most of the available numerical data is discarded. In turn, this may lead to subtle physiological changes being missed when investigating the cardiovascular system, over time. We have developed a mathematical method (Symmetric Projection Attractor Reconstruction) which uses all the numerical data, replotting and re-visualising it in a manner that allows unique quantification of multiple changes in waveform morphology and variability. We propose that the additional quantification of these features will allow the complex behaviour of the cardiovascular system to be more sensitively mapped under different physiological and pathophysiological settings. This article is protected by copyright. All rights reserved.
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The diurnal rhythms of sodium handling and blood pressure are thought to be regulated by clock genes, such as Bmal1. However, little is known about the regulation of these factors by Bmal1, especially in rats. Using a novel whole-body Bmal1 knockout rat model (Bmal1-/-), we hypothesized that time of day regulation of sodium excretion is dependent on Bmal1. Using telemetry to continuously record mean arterial pressure, we observed that male and female Bmal1-/- rats had significantly reduced mean arterial pressure over the course of 24 hours compared with littermate controls. The circadian mean arterial pressure pattern remained intact in both sexes of Bmal1-/- rats, which is in contrast to the Bmal1-/- mouse model. Male Bmal1-/- rats had no significant difference in baseline sodium excretion between 12-hour active and inactive periods, indicating a lack of diurnal control independent of maintained mean arterial pressure rhythms. Female Bmal1-/- rats, however, had significantly greater sodium excretion during the active versus inactive period similar to controls. Thus, we observed a clear dissociation between circadian blood pressure and control of sodium excretion that is sex dependent. These findings are consistent with a more robust ability of females to maintain control of sodium excretion, and furthermore, demonstrate a novel role for Bmal1 in control of diurnal blood pressure independent of sodium excretion.
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Circadian rhythms are an inherent property of physiological processes and can be disturbed by irregular environmental cycles, including artificial light at night (ALAN). Circadian disruption may contribute to many pathologies, such as hypertension, obesity, and type 2 diabetes, but the underlying mechanisms are not understood. Our study investigated the consequences of ALAN on cardiovascular and metabolic parameters in spontaneously hypertensive rats, which represent an animal model of essential hypertension and insulin resistance. Adult males were exposed to a 12 h light - 12 h dark cycle and the ALAN group experienced dim light at night (1-2 lx), either for 2 or 5 weeks. Rats on ALAN showed a loss of light-dark variability for systolic blood pressure, but not for heart rate. Moreover, a gradual increase of systolic blood pressure was recorded over 5 weeks of ALAN. Exposure to ALAN increased plasma insulin and hepatic triglyceride levels. An increased expression of metabolic transcription factors, Pparα and Pparγ, in the epididymal fat and a decreased expression of Glut4 in the heart was found in the ALAN group. Our results demonstrate that low-intensity ALAN can disturb blood pressure control and augment insulin resistance in spontaneously hypertensive rats, and may represent a serious risk factor for cardiometabolic diseases.
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Introduction: A volume-pressure sensor and tail-cuff method for monitoring blood pressure is non-invasive and inexpensive. This method requires animals to be restrained or subjected to anesthesia, but comparative effects of these manipulations on hemodynamic parameters have not been documented. Methods: Using a volume-pressure sensor and tail-cuff, we serially measured blood pressure and heart rate in normotensive adult male Lewis rats after light isoflurane-induced anesthesia (5% induction, 1% maintenance) and, following untrained restraint. Blood pressure was recorded until the acquisition of three complete measurements without the range of replicate mean arterial pressures exceeding 15 mmHg (steady-state). Results: Averages for the entire series of consecutive measurements indicated that restraint yielded significantly higher systolic and diastolic blood pressure than anesthesia (P < .05), but heart rate was not affected. Following stabilization at steady-state, there were no significant differences in intra- or inter-day hemodynamic values between the restraint and isoflurane groups. The inter-day coefficient of variation for systolic pressure was 13-23% for isoflurane and 9-14% for restraint. Bland-Altman analysis showed wide limits of agreement (±59 mmHg systolic; ±49 mmHg diastolic pressure) between restraint and isoflurane measurements. Discussion: Isoflurane caused more variability but there was agreement in BP evaluation by the isoflurane and restraint methods. Using the VPR system, light isoflurane-induced anesthesia and restraint could effectively be used to screen and quantify overt changes in hemodynamic parameters for cardiovascular research utilizing laboratory rodents.
Article
Aims: Cardiovascular parameters exhibit significant 24-h variability, which is coordinated by the suprachiasmatic nucleus (SCN), and light/dark cycles control SCN activity. We aimed to study the effects of light at night (ALAN; 1-2 lx) on cardiovascular system control in normotensive rats. Main methods: Heart rate (HR) and blood pressure (BP) were measured by telemetry during five weeks of ALAN exposure. From beat-to-beat telemetry data, we evaluated spontaneous baroreflex sensitivity (sBRS). After 2 (A2) and 5 (A5) weeks of ALAN, plasma melatonin concentrations and the response of BP and HR to norepinephrine administration were measured. The expression of endothelial nitric oxide synthase (eNOS) and endothelin-1 was determined in the aorta. Spontaneous exploratory behaviour was evaluated in an open-field test. Key findings: ALAN significantly suppressed the 24-h variability in the HR, BP, and sBRS after A2, although the parameters were partially restored after A5. The daily variability in the BP response to norepinephrine was reduced after A2 and restored after A5. ALAN increased the BP response to norepinephrine compared to the control after A5. Increased eNOS expression was found in arteries after A2 but not A5. Endothelin-1 expression was not affected by ALAN. Plasma melatonin levels were suppressed after A2 and A5. Spontaneous exploratory behaviour was reduced. Significance: ALAN decreased plasma melatonin and the 24-h variability in the haemodynamic parameters and increased the BP response to norepinephrine. A low intensity ALAN can suppress circadian control of the cardiovascular system with negative consequences on the anticipation of a load.
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Recently, by utilizing conventional and tamoxifen inducible Bmal1 (Brain and muscle Arnt-like protein 1) knockout mice, we found that delaying the loss of circadian rhythms to adulthood attenuates the impact on general integrity and survival at least under 12h light/12h dark conditions (LD). To understand further the contribution of Bmal1 in post-natal life under conditions of circadian disruption, we subjected inducible knockout mice (KO) and their littermate controls (Ctrl) to forced desynchrony protocols including cycles with non-24h periods, randomized light/dark cycles, and jet lag, and monitored their locomotor activity using radiotelemetry. Under these conditions, control mice cannot be entrained, as reflected by their maintenance of circadian behavior irrespective of schedules. By contrast, KO mice displayed higher activity levels in the dark phases of most cycles. Under a 3h light/3h dark regime, Ctrls displayed higher activity levels in the dark phases of all cycles although there were still obvious circadian rhythms, suggesting that an ultradian mechanism is also involved. Insulin sensitivity was markedly reduced by disrupted light schedules as expected in Ctrls, but not in the KOs. Thus, Bmal1 deletion in adult mice facilitates adaptation to new light/dark schedules and protects from insulin resistance induced by circadian disruption.
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The Earth turns on its axis every 24 h; almost all life on the planet has a mechanism — circadian rhythmicity — to anticipate the daily changes caused by this rotation. The molecular clocks that control circadian rhythms are being revealed as important regulators of physiology and disease. In humans, circadian rhythms have been studied extensively in the cardiovascular system. Many cardiovascular functions, such as endothelial function, thrombus formation, blood pressure and heart rate, are now known to be regulated by the circadian clock. Additionally, the onset of acute myocardial infarction, stroke, arrhythmias and other adverse cardiovascular events show circadian rhythmicity. In this Review, we summarize the role of the circadian clock in all major cardiovascular cell types and organs. Second, we discuss the role of circadian rhythms in cardiovascular physiology and disease. Finally, we postulate how circadian rhythms can serve as a therapeutic target by exploiting or altering molecular time to improve existing therapies and develop novel ones.
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Chronic obstructive pulmonary disease (COPD) is one of the causes of mortality worldwide with an increasing prevalence. Heart rate variability (HRV) reflects the regulation mechanism of the cardiac activity by the autonomic nervous system. The assessment of HRV by using nonlinear methods is more sensitive for the detection of complexity when compared to linear methods. This study aims to get information about the autonomic dysfunction occurred in patients with COPD by analysing the complexity of HRV. Electrocardiogram signals recorded from healthy subjects, patients with moderate COPD and severe COPD (eight subjects per group) were analysed. The HRV signals were acquired from ECG signals. Signals were reconstructed in the phase space and largest Lyapunov exponent (LLE), correlation dimension, Hurst exponent and approximate entropy (ApEn) values were calculated. It has seen that for the patients with COPD LLE, correlation dimension, Hurst exponent and ApEn values were less than control group. According to this, HRV complexity decreases in the presence of COPD. However, there is no significant difference between COPD groups and the severity of COPD has no effect on the chaoticity of the system. The results revealed that autonomic dysfunction occurred in patients with COPD is associated with reduced HRV complexity.
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Introduction: A newly developed total implant telemetry system for cardiovascular (CV), electrophysiological and body temperature measurement was evaluated. A cloud-based transmission of the physiological signals allowed an assessment of the quality of the physiological signals despite the physical separation between the instrumented animals and the evaluating home laboratory. The new system is intended to be used for safety pharmacological evaluations of drug candidates in various species. Methods: Two female minipigs, 6 Labrador-mixed breed dogs and 4 female Cynomolgus monkeys were instrumented with a newly developed total implant system (TSE SYSTEMS). The implants feature a microprocessor, internal memory (1 GB), 2 solid state pressure-tipped catheters, amplifiers and a radio transmitter. Sampling rates for each measurement can be selected within a range between 0.1 and 1 kHz. Biological signals are selected in a programmable fashion on a session-by-session basis according to a user-defined protocol. The pressure sensors are at the tip of an electrical lead having a length customized to each species. Core temperature measurement and activity monitoring (3D accelerometer) are included in the system. Digital transmission range using a single antenna is 5 m with up to 16 animals held together and monitored simultaneously. The range can be expanded with more antennas in an array coupled to a single receiver. The antenna/receiver station consists of a single USB powered mobile unit connected to a PC or laptop. The battery life provides 110 days of continuous recording. The dogs and minipigs were instrumented and monitored in Germany. A novel cloud-based data transmission system was developed to monitor the physiological signals in real-time from the Cynomolgus monkeys, still kept in Mauritius, from the data evaluation laboratory in Germany. After recovery from the surgical implantation, aortic pressure (AP), left ventricular pressure (LVP), ECG and body temperature were recorded for 24 hr monitoring sessions in all animals. Additionally, moxifloxacin (10, 30 and 100 mg/kg) was tested in the dog model using a modified Latin square cross-over study design. Results: The implant was well tolerated and the animals recovered rapidly from the implantation procedure. Excellent signal quality was obtained and stable hemodynamic and electrophysiological parameters could be measured, with little signal artefact or drop-out, over 24 h in each species. After oral dosing of moxifloxacin to the dogs, a substantial, dose-dependent increase in the QT-interval duration could be shown, as anticipated for this agent. Cloud-based data acquisition from the animals in Mauritius and the data evaluation lab in Germany worked well. Conclusion: This new CV telemetry system provides a novel alternative to fluid-filled catheter telemetry systems and the coupling to a cloud-based data transmission allows for flexibility in the location of the instrumented animals and data acquisition and the location of the site for data analysis. For the first time it is technically feasible to conduct a CV safety pharmacology study in Cynomolgus monkeys without having to ship them long distances to the home laboratory.
Article
Study design: Experimental Study. Objectives: To characterize the specific hindlimb electromyographic (EMG) patterns in response to muscle stretch and to measure the applied forces during stretching in the rat model of moderate SCI. Setting: Kentucky Spinal Cord Injury Research Center, Louisville, KY, USA. Methods: Female Sprague Dawley rats (n = 4) were instrumented for telemetry-based EMG recording (right rectus femoris and biceps femoris) and received a moderate T10 spinal cord injury (SCI). The major hindlimb muscle groups were stretched using our clinically modeled protocol. The EMG responses were recorded biweekly for 8 weeks. The forces applied during stretching were measured using a custom-designed glove. Locomotor function was assessed using the BBB Open Field Locomotor Scale, 3D kinematics and gait analysis. Results: Three main EMG patterns in response to stretch were identified: clonic-like, air-stepping, and spasms. Torques applied during stretching ranged from 0.4-8 N•cm, and with the exception of the quadriceps, did not change significantly over the weeks of stretching. Two stretching sessions a week did not result in a significant disruption to locomotor function. Conclusions: Stretching evokes EMG patterns in rats similar to those reported in humans including clonus and spasms. The torques used during stretching are comparable, based on the ratio of torque to body weight, to the few previously published studies that measured the forces and/or torques applied by physical therapists when stretching patients. Future studies are warranted to fully explore the impact of muscle stretch on spinal cord function after injury. Sponsorship: DoD, KSCHIRT, NIH.
Article
Aims: Stromal interaction molecule 1 (STIM1) has emerged as an important player in the regulation of growth and proliferation of smooth muscle cells. Therefore, we hypothesized that STIM1 plays a crucial role in the maintenance of vascular integrity. The objective of this study was to evaluate whether reduced expression of STIM1 could modify the structure and function of the vasculature, leading to changes in blood pressure (BP). Methods and results: Smooth muscle-specific STIM1 knockout (sm-STIM1 KO) in mice resulted in arteries with ∼80% reduced STIM1 protein expression as compared to control mice. Mesenteric vessels exposed to increasing transmural pressure revealed attenuated myogenic reactivity and reduced vasoconstrictor response to phenylephrine in sm-STIM1 KO arteries. BP monitored via telemetry in sm-STIM1 KO and matched controls did not reveal differences. However, heart rate was significantly increased in sm-STIM1 KO mice. Consistent with these findings, plasma catecholamine levels were higher in sm-STIM1 KO than in control mice. Increased sympathetic activity in sm-STIM1 KO mice was unmasked by apha1-adrenergic receptor inhibitor (prazosin) and by treatment with the ganglion-blocking agent, hexamethonium. Both treatments resulted in a greater reduction of BP in sm-STIM1 KO mice. Cytoskeleton of cultured smooth muscle cells was studied by immunocytochemistry using specific antibodies. Staining for actin and vinculin revealed significant alterations in the cytoskeletal architecture of cells isolated from sm-STIM1 KO arteries. Finally, although sm-STIM1 KO mice were protected from Ang II-induced hypertension, such treatment resulted in significant fibrosis and a rapid deterioration of cardiac function. Conclusions: STIM1 deletion in smooth muscle results in attenuated myogenic tone and cytoskeletal defects with detrimental effects on the mechanical properties of arterial tissue. Although BP is maintained by elevated circulating catecholamine, this compensatory stimulation has a deleterious long-term effect on the myocardium.
Article
Physiological variables such as heart rate (HR) and blood pressure (BP) exhibit long-term circadian rhythms, which can be disturbed by shift work. On the other hand, short-term oscillations in HR and BP have a high prognostic value. Therefore, we aimed to determine if the short-term variability, complexity and entropy of HR and BP would be affected by a regular light/dark (LD) cycle and phase delay shifts of the LD cycle, leading to chronodisruption. Telemetry-monitored rats were exposed first to the regular LD cycle and then to shifts in LD for 8 weeks. On the basis of long-term HR and BP recording and evaluation, we found circadian rhythms in HR and BP variability, complexity and entropy under regular LD cycles. Short-term exposure to shifts disturbed circadian rhythms of HR and BP variability, complexity and entropy, indicating chronodisruption. The power of circadian rhythms was suppressed after 8 weeks of phase delay shifts. Long-term exposure to shifts increased variability (p = 0.007), complexity (p < 0.001) and dark-time entropy (p = 0.006) of HR but not BP. This is the first study demonstrating long-term recording and estimation of HR and BP variability, complexity and entropy in conscious rats exposed to irregular lighting conditions. After long-term phase delay shifts, short-term variability of HR was less predictable than in controls. This study suggests that changes in short-term HR and BP oscillations induced by long-term shift work can negatively affect cardiovascular health.
Article
Inbred strains of rats can be used as models of human hypertension to evaluate mechanisms of regulation of the circadian rhythms underlying hypertension. Blood pressure and heart rate rhythms in rodents are endogenous (circadian). Studies have been performed in rats on the turnover of norepinephrine, on processes of signal transduction in the beta-adrenoceptor-adenylate cyclase-cyclic AMP-phosphodiesterase system and in the renin-angiotensin-aldosterone system, and on circadian rhythms in blood pressure and heart rate using radiotelemetry. The findings allowed a better understanding of the circadian phase-dependent kinetics and effects of cardiovascular active drugs (chronopharmacology) used in humans.
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Heart rate variability (HRV) has been extensively explored by traditional linear approaches (e.g. spectral analysis). However, several studies have pointed to the presence of nonlinear features in HRV, suggesting that linear tools might fail to account for the complexity of the HRV dynamics. Even though the prevalent notion is that HRV is nonlinear, the actual presence of nonlinear features is rarely verified. In this study, the presence of nonlinear dynamics was checked as a function of time scales in three experimental models of rats with different impairment of the cardiac control, namely rats with heart failure (HF), spontaneously hypertensive rats (SHRs) and sinoaortic denervated (SAD) rats. Multiscale entropy (MSE) and refined MSE (RMSE) were chosen as discriminating statistic for the surrogate test utilized to detect nonlinearity. Nonlinear dynamics is less present in HF animals at both short and long time scales compared to controls. A similar finding was found in SHR only at short time scales. SAD increased the presence of nonlinear dynamics exclusively at short time scales. Those findings suggest that a working baroreflex contributes to linearize HRV and to reduce the likelihood to observe nonlinear components of the cardiac control at short time scales. In addition, an increased sympathetic modulation seems to be a source of nonlinear dynamics at long time scales. Testing nonlinear dynamics as a function of the time scales can provide a characterization of the cardiac control complementary to more traditional markers in time, frequency and information domains.
Article
Disturbances in regular circadian oscillations can have negative effects on cardiovascular function, but epidemiological data are inconclusive and new data from animal experiments elucidating critical biological mechanisms are needed. To evaluate the consequences of chronic phase shifts of the light/dark (LD) cycle on hormonal and cardiovascular rhythms, two experiments were performed. In Experiment 1, male rats were exposed to either a regular 12:12 LD cycle (CONT) or rotating 8-h phase-delay shifts of LD every second day (SHIFT) for 10 weeks. During this period, blood pressure (BP) was monitored weekly, and daily rhythms of melatonin, corticosterone, leptin and testosterone were evaluated at the end of the experiment. In Experiment 2, female rats were exposed to the identical shifted LD schedule for 12 weeks, and daily rhythms of BP, heart rate (HR) and locomotor activity were recorded using telemetry. Preserved melatonin rhythms were found in the pineal gland, plasma, heart and kidney of SHIFT rats with damped amplitude in the plasma and heart, suggesting that the central oscillator can adapt to chronic phase-delay shifts. In contrast, daily rhythms of corticosterone, testosterone and leptin were eliminated in SHIFT rats. Exposure to phase shifts did not lead to increased body weight and elevated BP. However, a shifted LD schedule substantially decreased the amplitude and suppressed the circadian power of the daily rhythms of BP and HR, implying weakened circadian control of physiological and behavioural processes. The results demonstrate that endocrine and cardiovascular rhythms can differentially adapt to chronic phase-delay shifts, promoting internal desynchronization between central and peripheral oscillators, which in combination with other negative environmental stimuli may result in negative health effects.
Article
Analysis of heart rate variability (HRV) is performed through interbeat interval time series derived from either electrocardiographic or arterial pressure (AP) recordings. However, little attention has been given to the reliability of calculating the time series from different sources, i.e. electrocardiogram (ECG) or pulse intervals (PI). Therefore, the present study aimed to evaluate the correlation between interbeat interval time series obtained from RR, inter-systolic (SS) and inter-diastolic (DD) intervals, as well as their impact on indices of HRV calculated from series of RR or PI. Conscious rats previously instrumented with subcutaneous electrodes and a catheter into the femoral artery were subjected to simultaneous ECG and AP recording for 5 min. Correlation and Bland-Altman plots between RR and PI were evaluated. Moreover, HRV was analyzed in time (mean cardiac interval, SDNN and RMSSD) and frequency domain (power in LF and HF spectral bands) as well as by nonlinear approaches (symbolic dynamics and sample entropy). First, RR showed a stronger correlation with PI calculated by DD than SS. Second, most HRV indices showed similar results when calculated with RR or DD series, but not with SS series. Considering RR interval as the gold standard for the calculation of cardiac cycle, when using PI inter diastolic intervals are the better choice to study HRV. These findings are quite relevant, especially when AP recording is used for HRV analysis.
Article
Comprehensive cardiovascular assessment in conscious rodents by utilizing telemetry has been limited by the restriction of current devices to one pressure channel. The purpose of this study was to test and validate a dual pressure transmitter that allows the simultaneous measurement of arterial pressure (AP) and left ventricular pressure (LVP) in conscious freely moving rats. Six rats were surgically implanted with dual pressure transmitters. Baseline hemodynamics and circadian rhythm were observed to return within 7 days. AP, heart rate (HR), LVP and indices of left ventricular contractility were stable and demonstrated a prominent circadian rhythm over a two-week period of uninterrupted recordings. Administration of the vasodilator nifedipine produced the anticipated dose-dependent decrease in AP which was accompanied by a baroreflex mediated increase in HR and cardiac contractility. The negative inotrope verapamil produced the expected dose-dependent decreases in AP and cardiac contractility. Finally, a terminal validation of the dual pressure transmitter was performed under anesthesia by measuring AP and LVP simultaneously via telemetry and from a fluid filled arterial catheter and an intraventricular Millar catheter, respectively. A range of pressures and cardiac contractility were studied by administering sequential intravenous infusions of the positive inotrope dobutamine followed by verapamil. Linear regression analysis revealed a high level of agreement between pressures measured by the dual pressure transmitter and the exteriorized catheters. Histopathologic analysis of the heart revealed mild peri-catheter fibrosis. In conclusion, the simultaneous measurement of AP and LVP offers the potential for more detailed cardiovascular assessment in conscious rats.
Article
Decreased oxygenation during pregnancy and early periods of ontogeny can affect normal body development and result in diseases in adulthood. The aim of this study was to use the model of prenatal intermittent hypoxia (PIH) and evaluate the effects of short-term hypoxia at the end of gestation on blood pressure (BP) control in adulthood. Wistar rats were exposed daily to PIH for 4 h during gestational day 19 and 20. In adult male rats, heart rate (HR), systolic BP and pulse pressure (PP) were acquired by radiotelemetry during 1 week. On the basis of HR variability and BP variability, sympathovagal balance (LF/HF) and spontaneous baroreflex sensitivity (sBRS) were evaluated. Systolic BP and PP were significantly elevated in PIH rats in comparison with control rats during the light and dark phase of the day, while LF/HF increased only during the light phase of the day. In contrast, sBRS tended to decrease only during the dark phase in PIH rats. In all measured and calculated parameters, significant circadian rhythms were present and were not affected by PIH. In conclusion, our data suggest that short intermittent hypoxia at the end of gestation can increase BP and PP via significant changes in LF/HF, which occur especially during the passive phase of the day. Results suggest that minor changes in the autonomous nervous system activity induced by environmental conditions during the perinatal period may contribute to development of hypertension in adulthood.Hypertension Research advance online publication, 25 February 2016; doi:10.1038/hr.2016.21.
Article
The first aim of this study was to establish a surgical procedure to implant a new telemetric device for the continuous recording of electrocardiogram (ECG) and blood pressure (BP) in freely moving pigs. A second aim was the functional assessment of cardiovascular parameters, including heart rate variability (HRV) and blood pressure variability (BPV), so that these data could be used as the basis for the objective evaluation of autonomic activity and balance in different behavioural contexts. Eleven domestic pigs (German Landrace) underwent surgery for the placement of a telemetric device. At day 15 after surgery, 512 consecutive inter-beat intervals and pressure waves were analysed using different detection methods (automatic and manually corrected) while the animals were resting or feeding, respectively. HRV and BPV were calculated. Incomplete datasets were found in four pigs due to missing ECG or BP signals. Technical and surgical issues concerning catheterisation and detachment of the negative ECG lead were continuously improved. In the remaining pigs, excellent signal quality (manually corrected data of 1%) was obtained during resting and acceptable signal quality (<10%) was obtained during feeding. Automatic triggering was sufficiently reliable to eliminate errors in BP recordings during active behaviour, but this was not the case for ECG recordings. Sympathetic arousal with accompanying vagal withdrawal during feeding was documented. The established surgical implantation and functional assessment of the telemetric system with the reliable registration of cardiovascular parameters in freely moving pigs could serve as a basis for future studies of autonomic regulation in context of stress and animal welfare.
Article
Autonomic nervous system dysfunction is common after acute stroke and is associated with elevated risk of cardiac arrhythmia and mortality. Heart rate variability and baroreceptor sensitivity have been investigated as parameters of autonomic nervous system dysfunction for the prediction of stroke outcome. We performed a systematic literature review on heart rate variability and baroreceptor sensitivity as parameters for autonomic nervous function in acute stroke. Twenty-two studies were included. Associations between heart rate variability or baroreceptor sensitivity and stroke severity, early and late complications, dependency and mortality were reported. However, interpretability of most studies and extrapolation to general stroke population are limited due to many confounding factors such as varying methodology, small sample sizes, survival selection, and exclusion of patients with frequently occurring comorbidities in stroke. Key issues, such as the effect of thrombolytic therapy on autonomic function, autonomic nervous system dysfunction in the hyperacute phase of stroke, and correlation with the risk of recurrent stroke have not been investigated. Also, nonlinear techniques have remained largely unexplored in this domain, in spite of their advantage to provide more solid evaluation in the occurrence of arrhythmia. Cardiac autonomic dysfunction, represented by reduced heart rate variability or impaired baroreceptor sensitivity, is associated with stroke severity, early and late complications, dependency, and mortality. Large-scale prospective studies applying internationally accepted standards of measures for analysis of heart rate variability and baroreceptor sensitivity are needed in patients with acute stroke. © 2015 World Stroke Organization.
Article
The effect of endotoxin on heart rate variability (HRV) was assessed in diabetic and controls rats using a telemetric system. Endotoxin induced a reduction in sample entropy of cardiac rhythm in control animals. However, this effect was significantly blunted in streptozotocin-induced diabetic rats. Since uncoupling of cardiac pacemaker from cholinergic control is linked to reduced HRV in endotoxemia, chronotropic responsiveness to cholinergic stimulation was assessed in isolated atria. Endotoxemia was associated with impaired responsiveness to carbacholine in control rats. However, endotoxemia did not impair cholinergic responsiveness in diabetic atria. These findings corroborates with development of endotoxin tolerance in diabetic rats. Copyright © 2014 Elsevier B.V. All rights reserved.